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1.
Brenda Costall Simon J. Gunning Robert J. Naylor 《Naunyn-Schmiedeberg's archives of pharmacology》1982,319(3):226-230
Summary Nanomolar concentrations of apomorphine caused contractions of the circular smooth muscle from the body region of the guinea-pig stomach, the response showing rapid tachyphylaxis. These contractions were antagonised by yohimbine but not by prazosin, haloperidol, propranolol or methysergide. Higher concentrations of apomorphine caused concentration-related relaxations of the stomach body which were not subject to tachyphylaxis. These were antagonised by propranolol but not by prazosin, yohimbine or haloperidol. Dopamine-induced contractions of the circular smooth muscle from the stomach body were antagonised by apomorphine in nanomolar concentration; acetylcholine-induced contractions and isoprenaline-, dopamine- and phenylephrine-induced relaxations were unaffected by apomorphine. Thus, it is concluded that the contraction of circular smooth muscle from the stomach body to apomorphine is mediated via an adrenoceptor with characteristics of the 2-type, and that a partial agonist-antagonists action prevents subsequent contractile responses to apomorphine and dopamine. Relaxation caused only at higher concentrations of apomorphine is mediated via an adrenoceptor with characteristics of the -type. 相似文献
2.
E. Schlicker M. Kathmann M. Detzner H. J. Exner M. Göthert 《Naunyn-Schmiedeberg's archives of pharmacology》1994,350(1):34-41
The effects of 2-adrenoceptor agonists (dexmedetomidine, oxymetazoline), alone or in combination with various -adrenoceptor subtype-selective antagonists (CH-38083, idazoxan, WB4101, BRL44408, ARC-239, prazosin), on noradrenaline- and isoprenaline-induced lipolysis were investigated in human isolated abdominal subcutaneous fat cells. The rank order of potency of antagonists in preventing dexmedetomidine- and oxymetazoline-evoked suppression of isoprenaline-induced lipolysis was (pA2-values): CH-38083 (7.69 and 7.48) idazoxan (7.5 and 7.41) > BRL 44408 (7.23 and 7.19) WB 4101 (7.13 and 7.12) > prazosin (5.18 and 5.17) > ARC-239 (4.72, 4.9). While CH-38083 and idazoxan, non-subtype selective 2-adrenoceptor antagonists and BRL44408, a selective a2A-adrenoceptor antagonist as well as WB4101 potentiated the lipolytic effect of noradrenaline, ARC-239, the selective 2B-adrenoceptor antagonist failed to affect it. In addition since the 2A-adrenoceptor selective agonist, oxymetazoline concentration dependently inhibited the lipolytic effect of isoprenaline, and WB4101 and BRL44408 (a2A-adrenoceptor antagonists) antagonised the effect of oxymetazoline in a competitive manner, it is concluded that the a2A-adrenoceptor subtype is involved in antilipolysis. In addition, functional evidence was obtained that there is an interaction between 2A- and -adrenoceptors located on the cell surface of adipocytes, through which locally released noradrenaline and/or circulating circulating adrenaline influence lipolysis.On leave from Institute of Medical Pharmacology, University of Pisa, Via Roma 55, I-5626 Pisa, Italy
Correspondence to: E. S. Vizi at the above address 相似文献
3.
Owen L. Woodman 《Naunyn-Schmiedeberg's archives of pharmacology》1991,343(1):65-69
Summary The effect of the intra-coronary (i.c.) injection of nicotine on large coronary artery diameter and coronary blood flow was examined in anaesthetized dogs. In sixteen untreated dogs nicotine (20 g i.c.) had a biphasic effect on arterial pressure (initial increase, 7 ± 2 mmHg; secondary decrease, –8 ± 3 mmHg) which was accompanied by small and variable effects on heart rate and an increase in LV dP/dt. Nicotine increased large coronary artery diameter by 5.8 ± 0.8% but had a biphasic effect on coronary blood flow (initial increase, 41 ± 7 ml/min; secondary decrease, –10 ± 2 ml/min). Bilateral vagotomy or muscarinic receptor blockade with atropine (0.1 mg/kg i. v.) did not significantly affect the nicotine-induced changes in coronary artery diameter or coronary blood flow. The additional antagonism of -adrenoceptors with propranolol (1 mg/kg i. v.) abolished the effect of nicotine in coronary artery diameter ( CD = 0.2 ± 0.2%) and the initial increase in coronary blood flow ( CBF = 1 ± 1 ml/min) but enhanced the secondary decrease in flow ( CBF = –25 ± 3 ml/min). The nicotine-induced decrease in coronary blood flow observed after muscarinic and -adrenoceptor blockade was attenuated by antagonism of 1-adrenoceptors with prazosin (10 g/kg i. c., CBF = –15 ± 3 ml/min) and abolished after additional antagonism of 2-adrenoceptors with idazoxan (50 g/kg i. c., CBF = –2 ± 1 ml/min). These results indicate that in the anaesthetized dog intra-coronary injection of nicotine results in -adrenoceptor mediated dilatation of both large and small coronary arteries. In the coronary resistance vessels, but not in the large coronary artery, the dilatation is opposed by 1-and 2-adrenoceptor mediated vasoconstriction.
Send offprint requests to O. L. Woodman at the above address 相似文献
4.
Lesley J. Bryan-Lluka Helen E. Vuocolo 《Naunyn-Schmiedeberg's archives of pharmacology》1992,346(4):399-404
Summary Previous studies (Bönisch et al. 1985; Trendelenburg 1986, 1987) have provided evidence that Uptake2 of catecholamines is inhibited by depolarization of cells. The aim of this study was to further examine the relationship between Uptake2 and membrane potential by testing the hypothesis that Uptake2 is, conversely, stimulated by hyperpolarization of cells. The effects of -adrenoceptor agonists (isoprenaline and salbutamol) and -adrenoceptor antagonists (propranolol and ICI 118,551) on Uptake2 of isoprenaline were examined in guinea-pig trachealis muscle, in which stimulation of -adrenoceptors mediates hyperpolarization of the smooth muscle cells (Allen et al. 1985), and in rat heart, in which -adrenoceptor agonists do not cause hyperpolarization.In guinea-pig trachealis muscle segments, propranolol and ICI 118,551 reduced Uptake2 (as measured by the steady-state rate of corticosterone-sensitive formation of 3-O-methylisoprenaline normalized for the isoprenaline concentration) in tissues incubated in 2.5–250 nmol/l 3H-isoprenaline (in the range over which isoprenaline causes hyperpolarization of the muscle), but not in 1 nmol/l 3H-isoprenaline (which does not hyperpolarize the muscle). The normalized rates were greater in tissues incubated in 25 nmol/l than 1 nmol/l isoprenaline, and were enhanced by 2.5 gmol/l salbutamol in tissues incubated in 1 nmol/l isoprenaline. In rat hearts perfused with 1 or 25 nmol/l 3H-isoprenaline and U-0521 to inhibit catechol-O-methyltransferase, the rate of Uptake2 of isoprenaline, normalized for the isoprenaline concentration, was unaffected by the isoprenaline concentration or the presence of propranolol, ICI 118,551 or salbutamol.The results of the study suggest that, in guinea-pig trachealis muscle, isoprenaline and salbutamol enhance Uptake2 due to -adrenoceptor-mediated hyperpolarization of the muscle and that propranolol and ICI 118,551 decrease Uptake2 of isoprenaline by preventing this hyperpolarization of the smooth muscle, and not by directly inhibiting the Uptake2 transport process.
Correspondence to: L. J. Bryan-Lluka at the above addressSome of the results of this study were presented to the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (Vuocolo and Bryan-Lluka 1990) and the German Society for Pharmacology and Toxicology (Bryan-Lluka and Vuocolo 1991) 相似文献
5.
K. -H. Sontag P. Wand H. Cremer B. Mühlberg 《Naunyn-Schmiedeberg's archives of pharmacology》1974,286(3):315-318
Summary The -loop of pretibial flexor muscles was investigated before and after i.v. injection of 10 mg/kg DMAA in precollicular and prenigral decerebrate cats. DMMA reduces significantly the reflex discharge rate of Ia muscle spindle afferents, a result which might be important in regard of a hyperactive -motor system.Supported by the Deutsche Forschungsgemeinschaft, SFB 33. 相似文献
6.
K. -Fr. Sewing P. D. Gorinsky F. Lembeck 《Naunyn-Schmiedeberg's archives of pharmacology》1968,261(1):89-92
Summary 1. The effect of antigastrin (SC-15 396) on gastric acid and pepsin secretion produced by the gastrin-analogue tetrapeptide amide Try. Met. Asp. Phe-NH2 and by electrical stimulation of the vagus was investigated in anaesthetized gastric fistula cats.2. Antigastrin failed to inhibit both acid and pepsin response stimulated by either the tetrapeptide or vagus excitation.3. It was concluded that the ineffectiveness of antigastrin in cats is due to a species difference between rats and dogs on the one hand and cats on the other, and that antigastrin is not a specific gastrin antagonist.Supported by the Deutsche Forschungsgemeinschaft and by the Alfred Teufel-Stiftung. 相似文献
7.
H. R. Schwietert D. Wilhelm B. Wilffert P. A. van Zwieten 《Naunyn-Schmiedeberg's archives of pharmacology》1991,344(2):206-212
Summary The aim of the present investigation was to study, taking into account both quantitative and qualitative differences, the influence of full and partial -adrenoceptor agonists on spontaneous myogenic activity in the rat portal vein.We found that the -adrenoceptor agonists cirazoline, adrenaline, noradrenaline, phenylephrine, St 587, Sgd 101/75, B-HT 920 and UK-14,304 could increase the amplitude of the phasic myogenic contractions in the rat portal vein with apparent differences in EC50 and Emax values. In addition to an increase in phasic myogenic activity, the -adrenoceptor agonists cirazoline, adrenaline, noradrenaline, and phenylephrine were also able (in higher concentrations) to increase the basal tone of the rat portal vein preparation, again with apparent differences in EC50 and Emax values. Changing the extracellular Ca2+ concentration from 0.9 mmol/l to 2.5 mmol/1 had no influence on the phasic character and the concentration range in which St 587 and UK-14,304 increased spontaneous myogenic activity, although changes in amplitude and frequency of the spontaneous myogenic contractions were less pronounced at a higher extracellular Ca2+ concentration (2.5 mmol/1). By the use of Schild analysis with the competitive a-adrenoceptor antagonists prazosin (pA2 = 8.74) and 5-methyl-urapidil (pA2 = 8.37), it was established that the contractile responses to St 587 were mediated by the same 1-adrenoceptor subtype as the phasic and tonic type of contraction elicited by phenylephrine as described in a previous study. The concentration-response curve of UK-14,304 was significantly shifted to the right by low concentrations of prazosin (3 nmol/1–30 nmol/1), indicating stimulation of 1-adrenoceptors by UK-14,304 in the rat portal vein. The -adrenoceptor antagonists phenoxybenzamine and chloroethylclonidine irreversibly blocked the contractile responses to St 587. Based on the method of receptor alkylation with phenoxybenzamine an affinity constant was calculated for St 587 (pKa = 5.91). Phenoxybenzamine was approximately 1000-fold more potent in inactivating 1-adrenoceptors than chloroethylclonidine.In conclusion there appeared to be a divergence in the excitation-contraction coupling of 1-adrenoceptors in the rat portal vein, which is reflected by two types of contraction (phasic versus tonic). The extent to which both the phasic and tonic types of contraction are stimulated by agonists depends on the affinity and intrinsic efficacy for each of the receptor-coupled effector pathways. Thus, partial and full agonism can only meaningfully be discussed if confined to one particular effector pathway.
Send offprint requests to H. R. Schwietert at the above address 相似文献
8.
Summary The effects of noradrenaline (NA), adrenaline (Adr) and isoprenaline (Iso) on rat isolated uterus were studied, throughout the natural oestrous cycle. The -inhibitory effects of the catecholamines were measured as a percentage inhibition of a standard acetylcholine (ACh)-induced contraction. Iso produced approximately 80% maximum inhibition of the standard ACh-contraction in all 4 stages of the oestrous cycle. Adr and NA produced 80% maximum inhibition in oestrus only, and 50–60% maximum inhibition in proestrus, metoestrus and dioestrus. The differences in the degree of inhibition produced by the catecholamines were overcome (i.e. the maximum inhibition produced by Adr and NA was increased to become equal to that produced by Iso) when experiments were repeated in the presence of the uptake inhibitors desmethylimipramine (DMI) and normetanephrine (NMN), but not in the presence of an -adrenoceptor antagonist (azapetine 10–7 M). Variations in the uptake of3H-Iso and3H-NA were observed in the different stages of the oestrous cycle. Small -adrenoceptor mediated motor responses to NA and Adr were observed only in the presence of a -antagonist (propranolol 10–5 M), in uteri from rats in oestrus, metoestrus and dioestrus, but not proestrus. It is concluded that in the rat isolated uterus, -inhibitory receptors predominate throughout the natural oestrous cycle, although the existence of -excitatory receptors has been shown in 3 of the 4 stages. 相似文献
9.
H. C. Innemee A. de Jonge J. C. A. van Meel P. B. M. W. M. Timmermans P. A. van Zwieten 《Naunyn-Schmiedeberg's archives of pharmacology》1981,316(4):294-298
Summary The influence of topically applied selective 1- and 2-adrenoceptor agonists on intraocular pressure and the diameter of the pupil was investigated in conscious rabbits. Selective stimulation of the 1-subtype of receptors induced an elevation in intraocular pressure, accompanied by mydriasis, whereas stimulation of the 2-subtype caused a marked and dose-dependent ocular hypotensive response, which was blocked by the selective 2-adrenoceptor antagonist yohimbine. 2-Agonists induced neither macroscopic ocular side effects, nor an effect on the pupil size. Possibly, the subclass of 2-adrenoceptor stimulating drugs represent a group of new antiglaucomatous agents. 相似文献
10.
Rumiko Hosoki Tetsuhiro Hisayama Issei Takayanagi 《Naunyn-Schmiedeberg's archives of pharmacology》1987,335(3):290-295
Summary Contractile responses to neurokinin and neurokinin were characterized and compared with those to substance P (a SP-P agonist) and eledoisin (a SP-E agonist) in isolated rabbit iris sphincter. Neurokinin a and neurokinin as well as substance P and eledoisin produced atropine- and tetrodotoxin-resistant contractions of the iris sphincter in nanomolar concentrations, and the rank order of sensitivity was eledoisin > substance P = neurokinin = neurokinin . After prolonged cold-storage of the preparations, responses to capsaicin, a releaser of tachykinins from sensory nerve endings, were nearly absent, but responses of considerable magnitude to carbachol and the tachykinins persisted. On wash-out of the tachykinins, responses faded at characteristic rates (neurokinin a > eledoisin > neurokinin substance P). From the Schild analyses, [abetd-Arg1, abetd-Pro2, abetd-Trp7,9, Leu11]-substance P, a potent substance P antagonist, competitively antagonized the response to substance P, had no significant effect on the response to neurokinin , and antagonized the response to neurokinin and eledoisin in a more complex manner. Taken together, these results suggest that there coexist multiple receptor sites for mammalian tachykinins in rabbit iris sphincter smooth muscle.
Send offprint requests to I. Takayanagi at the above address 相似文献
11.
S. Guimarães M. Q. Paiva D. Moura 《Naunyn-Schmiedeberg's archives of pharmacology》1987,335(4):397-402
Summary In dog saphenous vein — a tissue possessing both postsynaptic 1- and 2-adrenoceptors — the effects of two selective 1-adrenoceptor agonists (phenylephrine and methoxamine) were compared with that of the selective 2-adrenoceptor agonist, UK-14,304, before and after phenoxybenzamine. Furthermore, the influence exerted by prazosin, yohimbine and verapamil on the effects of these agonists was also studied before and after phenoxybenzamine. In the absence of phenoxybenzamine, prazosin (56 nmol/l) caused a parallel shift of the concentration-response curves of both phenylephrine and methoxamine to the right (by 0.94 and 1.1 log units, respectively) and had no effect on the concentration-response curve of UK-14,304, while 20 nmol/l yohimbine caused a marked parallel shift of the concentration-response curve of UK-14,304 to the right (by 1.18 log units) and caused only minor displacements of those of phenylephrine and methoxamine (by 0.2 and 0.33 log units, respectively). After exposure of the strips to 30 nmol/l phenoxybenzamine, prazosin (56 nmol/l) caused small shifts of the concentration-response curves of both phenylephrine (by 0.36 log units) and methoxamine (by 0.31 log units) and did not change that of UK-14,304, while yohimbine (20 nmol/l) caused pronounced parallel shifts of the concentration-response curves (to the right) of all the agonists: phenylephrine (by 1.0 log units), methoxamine (by 0.93 log units) and UK-14,304 (by 1.28 tog units). When UK-14,304 was added to the bath during a sub-maximal contraction to phenylephrine it caused a further contraction almost up to the maximum; if this procedure was repeated after phenoxybenzamine (30 nmol/1), there was no further contraction to UK-14,304.In the absence of phenoxybenzamine, verapamil (5 mol/l) caused a parallel shift of the concentration-response curve of phenylephrine (or methoxamine) to the right and a non-parallel shift (with marked depression of the maximal effect) of that of UK-14,304. However, after phenoxybenzamine (30 nmol/l), the same concentration of verapamil caused non-parallel shifts of the concentration-response curves of the three agonists to the right with about equal depression of the maximal effects. We conclude that, after removal of 1-adrenoceptor reserve by phenoxybenzamine, the responses to selective 1-adrenoceptor agonists are predominantly 2-adrenoceptor-mediated. This may explain why under these conditions, the selective 1-and 2-adrenoceptor agonists are equally antagonized by calcium entry blockers.This work was supported by a grant from the University of Porto (Subsidio para acção de investigação no. 36/85)
Send offprint requests to S. Guimarães at the above address 相似文献
12.
Rainer Schulz Ron J. Oudiz Brian D. Guth Gerd Heusch 《Naunyn-Schmiedeberg's archives of pharmacology》1990,342(4):422-428
Summary -Adrenoceptor-mediated coronary vasoconstriction contributes to the initiation and aggravation of experimental and clinical myocardial ischaemia. However, the extent of 1- and 2-adrenoceptor-mediated constriction has not been characterized in the porcine coronary circulation despite the frequent use of this experimental model.Fifteen swine were anaesthetized with either -chloralose, enflurane or isoflurane to determine the amount of -adrenoceptor-mediated coronary constriction elicited by either the selective 1-adrenoceptor agonist methoxamine or the selective 2-adrenoceptor agonist azepexole. The left anterior descending coronary artery was cannulated and perfused by an external pump delivering constant blood flow from the carotid artery. Following bilateral cervical vagotomy and ß-adrenoceptor blockade with propranolol (2 mg kg–1), graded dosages of either one of the -adrenoceptor agonists (9–45 g kg–1 min–1) were infused into the coronary perfusion line while coronary arterial pressure (CAP) was measured through a distal side arm of the cannula to detect changes in coronary vascular resistance. Infusion of the -adrenoceptor agonists was terminated when systemic arterial pressure increased. Sonomicrometers were used to measure anterior left ventricular wall thickening for the assessment of regional contractile function. During methoxamine infusion, no increase in vascular resistance was observed during -chloralose, enflurane or isoflurane anaesthesia, whereas the infusion of azepexole increased CAP from 103 ± 31 mmHg to 120 ± 35 mmHg (-chloralose), from 101 ± 16 mmHg to 122 ± 11 mmHg (enflurane) and from 84 ± 20 mmHg to 94 ± 19 mmHg (isoflurane), respectively. In four additional swine anaesthetized with enflurane, the intracoronary infusion of the full catecholamine agonist noradrenaline in the presence of propranolol (6 mg kg–1) increased CAP from 98 ± 10 to 105 ± 10 mmHg prior to an increase in regional left ventricular function or systemic arterial pressure.These results indicate that there are no 1- and relatively little 2-adrenoceptor-mediated coronary constrictive effects in swine. Furthermore, neither -adrenoceptor agonist produced any detectable change in regional myocardial contractile function, regardless of the anaesthesia used.Supported by the German Research Foundation (He 1320/3-2). Dr. Guth is the recipient of a scholarship from the Alexander von Humboldt-Foundation.
Send offprint requests to G. Heusch at the above address 相似文献
13.
Ray W. Fuller Harold D. Snoddy Bryan B. Molloy Kenneth M. Hauser 《Psychopharmacology》1973,28(2):205-212
,-Difluorophenylethylamine, because of the strong electrophilic nature of the fluorines, is a much weaker base than is phenylethylamine. The pK for the difluoro compound is 6.75 compared to 9.55 for phenylethylamine. At physiologic pH, difluorophenylethylamine exists primarily as a neutral molecule, whereas phenylethylamine is almost entirely cationic. Difluorophenylethylamine caused increased locomotor activity in mice, and its effects were enhanced by a monoamine oxidase inhibitor (tranylcypromine) as were the effects of phenylethylamine. Comparable levels of difluorophenylethylamine and phenylethylamine in brain appeared to lead to equivalent increases in locomotor activity. At doses above those giving the maximum increase in locomotor activity, behavioral differences between phenylethylamine and difluorophenylethylamine were observed. Difluorophenylethylamine localized in adipose tissue to a greater degree than in other organs; it disappeared from adipose tissue and from brain with a physiologic half-life of 8 min in mice. 相似文献
14.
Maggi Carlo Alberto Patacchini Riccardo Perretti Francesca Meini Stefania Manzini Stefano Santicioli Paolo Del Bianco Elena Meli Alberto 《Naunyn-Schmiedeberg's archives of pharmacology》1990,341(1-2):74-79
Summary (1) We have studied the effect of epithelium removal (rubbing) and the endopeptidase 24.11 inhibitor, thiorphan, on the contractile response of the guinea-pig isolated bronchi (atropine and indomethacin in the bath) produced by electrical field stimulation, capsaicin or exogenously administered tachykinins (substance P and neurokinin A). (2) The response to field stimulation, thought to involve release of endogenous tachykinins, was potentiated by thiorphan in both epithelium-free and intact bronchi. However, at low frequencies (1–5 Hz), the effect of thiorphan was more evident in intact preparations. (3) The response to capsaicin was enhanced by both epithelium removal and thiorphan administration. (4) The response to exogenous substance P or neurokinin A was potentiated by thiorphan both in epithelium-free and intact bronchi. (5) Capsaicin (1 M) evoked a consistent release of substance P-like immumoreactivity (determined by radioimmunoassay) and tachykinin-like immumoreactivity (determined by a novel immumoenzyme assay), which was enhanced by thiorphan in both epithelium-free and intact bronchi. (6) These findings suggest that a thiorphan-sensitive mechanism, presumably enkephalinase (endopeptidase 24.11), plays a major role in inactivating endogenous tachykinins released from sensory nerves and that this enzymatic activity is still present after removal of the bronchial epithelium.
Send offprint requests to C. A. Maggi at the above address 相似文献
15.
M. Andréjak Y. Pommier P. Mouillé H. Schmitt 《Naunyn-Schmiedeberg's archives of pharmacology》1980,314(1):83-87
Summary The purpose of the present study was to further characterize the -adrenoceptors located on parasympathetic fibres. Segments of guinea-pig ileum were stimulated by transmural electrical pulses, and the ensuing contractions, which are due to the release of acetylcholine from postganglionic parasympathetic fibres, were monitored. Clonidine and tramazoline, which are thought to act preferentially on presynaptic -adrenoceptors, reduced the contractions, whereas phenylephrine and methoxamine, postsynaptic -adrenoceptor agonists, were ineffective. Contractions induced by acetylcholine were not changed by clonidine but were abolished by atropine. Yohimbine, piperoxan, phentolamine and thymoxamine reversed or prevented the inhibitory effect of clonidine. Prazosin and AR-C239 did not antagonize this effect. The inhibitory effect of tramazoline was antagonized by piperoxan but not by AR-C239 or by prazosin. Naloxone did not alter the action of clonidine, and piperoxan did not change the inhibitory effect of morphine.In conclusion, these experiments suggest the presence on cholinergic postganglionic fibres of both opiate receptors and -adrenoceptors. The latter appear to resemble more closely 1-adrenoceptors than 1-adrenoceptors. 相似文献
16.
Ezdihar A. M. Hassoun 《Archives of toxicology》1987,61(2):145-149
Interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and other ligands of theAh-receptor, had been studied in vivo, in pregnant NMRI mice, and in vitro, in the fetal thymus organ culture system. Benzo(a)pyrene (BP) increased TCDD-induced fetolethality, whereas it did not affect the rate of cleft palate formation. This may indicate that the mechanism of TCDD-induced fetal death is different from that of TCDD-induced cleft palate. 2,3,7,8-Tetrachlorodibenzofuran (TCDBF) and 3,3,4,4-tetrachloroazoxybenzene (TCAOB) were added together to the thymus organ culture, each at a concentration that caused about 25–50% lymphoid development inhibition. Such treatment resulted in an additive effect of about 75%. Similarly, when the slightly toxic -naphthoflavone (BN) was added together with TCDD to the same culture system, it caused a significant increase in the lymphoid inhibitory effect of the latter compound. These may all suggest a common mechanism of action for TCDD and other ligands, which may involve a direct interaction with the receptors present in the thymus.Abbreviations BN
-naphthoflavone
- BP
Benzo(a)pyrene
- PAH
Polycyclic aromatic hydrocarbons
- TCAOB
3,3,4,4-tetrachloroazoxybenzene
- TCDBF
2,3,7,8-tetrachlorodibenzofuran
- TCDD
2,3,7,8-tetrachlorodibenzo-p-dioxin 相似文献
17.
Norbert Limberger Anne-Ulrike Trendelenburg Klaus Starke 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(1):43-48
The study was devised to classify, by means of antagonist affinities, the presynaptic 2-autoreceptors in mouse cerebral cortex in terms of 2A, 2B, 2C and 2D. A set of antagonists was chosen that was able to discriminate between the four subtypes. Slices of the cortex were preincubated with 3H-noradrenaline and then superfused and stimulated electrically.The stimulation periods used (4 pulses, 100 Hz) did not lead to 2-autoinhibition as shown by the lack of an increase by rauwolscine of the evoked overflow of tritium. The 2-selective agonists 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and -methylnoradrenaline reduced the evoked overflow. All 10 antagonists shifted the concentration-inhibition curve of UK 14,304 to the right. Rauwolscine also shifted the concentration-inhibition curve of -methylnoradrenaline to the right. pKd values of the antagonists were calculated from the shifts. The pKd values of rauwolscine against UK 14,304 and -methylnoradrenaline were very similar (8.0 and 7.9, respectively).Comparison with antagonist affinities for prototypic native 2 binding sites, 2 binding sites in cells transfected with 2 subtype genes, and previously classified presynaptic 2-adrenoceptors — all taken from the literature — indicates that the 2-autoreceptors in mouse brain cortex are 2D. This is the first subtype determination of 2-autoreceptors in the mouse. It supports the hypothesis that at least the majority of 2-autoreceptors belong to the 2A/D branch of the 2-adrenoceptor tree. 相似文献
18.
Ludwig Funk Anne-Ulrike Trendelenburg Norbert Limberger Klaus Klaus 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(1):58-66
The study was designed to classify in terms of 2A, 2B, 2C and 2D the presynaptic 2-autoreceptors, as well as the 2-receptors modulating the release of acetylcholine, in the myenteric plexus-longitudinal muscle (MPLM) preparation of the guinea-pig ileum. A set of antagonists was chosen that was able to discriminate between the four subtypes. Small pieces of the MPLM preparation were preincubated with 3H-noradrenaline or 3H-choline and then superfused and stimulated electrically.The stimulation periods used (3H-noradrenaline: 3 trains of 20 pulses, 50 Hz, train interval 60 s; 3H-choline: single trains of 30 pulses, 0.2 Hz) did not lead to 2-autoinhibition or inhibition of 3H-acetylcholine release by endogenous noradrenaline. The 2-selective agonist 5-bromo6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) reduced the evoked overflow of tritium in both 3H-noradrenaline and 3H-choline experiments. Most (3H-noradrenaline) or all (3H-choline) of the 10 antagonists shifted the concentration-inhibition curves of UK 14,304 to the right. pKd values of the antagonists were calculated from the shifts. pKd values from 3H-noradrenaline experiments correlated with pKd values from 3H-choline experiments (r = 0.981).It is concluded that 2-autoreceptors and 2-heteroreceptors modulating the release of acetylcholine in the MPLM preparation are of the same subtype. Comparison with antagonist affinities for prototypic native 2 binding sites, binding sites in cells transfected with 2 subtype genes, and previously classified presynaptic 2-adrenoceptors — all taken from the literature — indicates that both are 2D. The results are consonant with the hypothesis that at least the majority of 2-autoreceptors belong to the 2A/D branch of the 2-adrenoceptor tree, across mammalian or at least across rodent and lagomorph species. The same may hold true for 2-adrenoceptors on non-noradrenergic neurones. 相似文献
19.
Hemendra N. Bhargava 《Psychopharmacology》1976,45(3):267-270
Mice were rendered morphine-dependent by the subcutaneous implantation of a pellet containing 75 mg of morphine base; 72 h after the implantation, the animals were injected intraperitoneally either with vehicle or with various doses of 9-tetrahydrocannabinol, 8-tetrahydrocannabinol, cannabidiol, cannabinol, or 11-hydroxy-8-tetrahydrocannabinol. Thirty minutes after injection of the cannabinoids, the antagonist, naloxone HCl, was administered to induce the stereotyped withdrawal jumping syndrome. The dose of naloxone needed to induce withdrawal jumping in 50% of the animals (ED50) was determined for each dose of the cannabinoids. All of the cannabinoids inhibited the naloxone-precipitated morphine abstinence as evidenced by an increase in the naloxone ED50. Two additional signs of morphine abstinence, defecation and rearing behavior, were also suppressed by the cannabinoids. The relative effectiveness of the cannabinoids in inhibiting morphine abstinence appeared to be in the following order: 9-tetrahydrocannabinol > 8-tetrahydrocannabinol > 11-hydroxy-8-tetrahydrocannabinol > cannabidiol > cannabinol.These data suggest that cannabinoids may be useful in facilitating narcotic detoxification. 相似文献
20.
The thermodynamic and kinetic limits of ethanol-enhanced estradiol skin transport have been investigated by studying the relationship between estradiol and ethanol steady-state flux in the cotransport of permeant and enhancer in situations in which there exists an enhancer solvent gradient across the skin (asymmetric configuration). For aqueous ethanol solution saturated with estradiol, the flux of estradiol across the human epidermal membrane is empirically observed to be linear with the ethanol flux. A physical model approach has been used to determine the basis of this empirical linearity and to predict permeant/enhancer transport across the skin for the asymmetric configuration. Enhancement factors, determined with a balanced ethanol concentration across the skin (symmetric configurations), are used to predict fluxes in the asymmetric configurations. The model demonstrates that ethanol enhances the stratum corneum transport of estradiol and of itself by increasing the respective diffusion coefficients at lower concentrations (<50%) and by both increasing the diffusion coefficients and decreasing the membrane activity coefficients at moderate concentrations (50 to 75%). The model also demonstrates that the permeant flux, in general, is not linear with the cotransported enhancer flux. 相似文献