首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到10条相似文献,搜索用时 156 毫秒
1.
Summary In pontine slices of the rat brain, the frequency of spontaneous action potentials of locus coeruleus (LC) neurones was recorded extracellularly. Noradrenaline 0.1–100 mol/l, UK 14,304 0.01–100 nmol/l, [Met5]-enkephalin 1–10,000 nmol/l and [D-Ala2, D-Leu5]enkephalin 0.1–1,000 nmol/l, all depressed the firing rate. Rauwolscine 1 mol/l antagonized the effects of both noradrenaline and UK 14,304, but potentiated the effects of [Met']enkephalin and [D-Ala2, D-Leu5]enkephalin. Idazoxan 1 mol/l acted in a similar manner. Prazosin 1 mol/l did not change the effects of either noradrenaline or [Met5]enkephalin. Naloxone 0.1 mol/l antagonized both [Met']enkephalin and [D-Ala2, D-Leu5]enkephalin, but failed to alter the effects of either noradrenaline or UK 14,304. Rauwolscine, idazoxan and prazosin, all 1 mol/l, as well as naloxone 0.1 mol/l, did not influence the firing rate when given alone. Desipramine 1 mol/l inhibited the discharge of action potentials in a rauwolscine-antagonizable manner. Noradrenaline 10 mol/l produced the same depression of firing, both in the presence of noradrenaline 1 mol/l and [Met5]enkephalin 0.03 mol/l. Likewise, the effect of [Met5]enkephalin 0.3 mol/l was the same, irrespective of whether it was added to a medium containing [Met5]enkephalin 0.03 mol/l or noradrenaline 1 mol/l. The spontaneous activity of LC neurones is inhibited by somatic 2-adrenoceptors and opioid -receptors. We suggest that the two receptors interact with each other at a site located between themselves and not in the subsequent common signal transduction system.Send offprint requests to: P. Illes at the above address  相似文献   

2.
Summary 1. The mechanism of uridine 5-triphosphate-(UTP-)induced vasoconstriction was studied in the rabbit ear artery. The arteries were incubated and perfused at a constant rate of flow. Vasoconstriction was measured as an increase in perfusion pressure. 2. Noradrenaline, adenosine 5'-triphosphate (ATP) and UTP caused concentration-dependent vasoconstriction. ATP and UTP were approximately equipotent. 3. The vasoconstrictor effect of UTP 300 mol/l was enhanced by a mixture of atropine, diphenhydramine and methysergide (1 mol/l each) and not affected by indometacin 10 mol/l. 4. Prazosin (0.01 –1 mol/l) and phentolamine (1–10 mol/l) reduced the vasoconstrictor effect of UTP 300 mol/l by up to 34%. Prazosin 1 mol/l failed to diminish the vasoconstrictor effect of UTP 300 mol/l after the sympathetic nerves had been destroyed with 6-hydroxydopamine. 5. , -Methylene-ATP (10–50 ol/l) elicited transient vasoconstriction. Subsequently, vasoconstrictor responses to ATP 100 or 300 pmol/1 were reduced by 88%, whereas responses to UTP 100 gmol/1 were enhanced, responses to UTP 300 mol/l decreased by only 32% and responses to UTP 1000 gmol/1 reduced by 74%. After in vitro-denervation with 6-hydroxydopamine or in the presence of phentolamine 1 mol/l throughout, a, -methylene-ATP (10–50 mol/l) reduced the vasoconstrictor effect of UTP 300 mol/l by 44% and 43%, respectively. 6. We suggest that, in the rabbit ear artery, the non-adrenergic and , -methylene-ATP-resistant vasoconstrictor response to UTP is mediated by a separate receptor mechanism, distinct from the P2 purinoceptor. Send offprint requests to K. Starke  相似文献   

3.
Summary The effects of the classical dopamine DA2-receptor agonist quinpirole (LY 171555) and the recently characterized DA2-receptor agonist, carmoxirole (EMD 45609), on neurotransmission in rat isolated kidney were investigated. After preincubation with 3H-noradrenaline, the renal nerves were electrically stimulated. The stimulation induced (S-I) outflow of radioactivity was taken as an index of noradrenaline release. Quinpirole (0.3 mol/l) inhibited S-I outflow of radioactivity and pressor responses to renal nerve stimulation (RNS) at 1 Hz. Both effects of quinpirole were blocked by the DA2-receptor antagonist S(–)-sulpiride (10 mol/l). The 1, 2-adrenoceptor antagonist phentolamine (1 mol/l) did not block the inhibitory effect of quinpirole. Carmoxirole (0.003 and 0.03 mol/l) did not alter and carmoxirole (0.3 mol/l) even enhanced S-I outflow of radioactivity, however, pressor responses to RNS were markedly reduced by carmoxirole (0.003–0.3 mol/l). Pressor responses to RNS were also markedly reduced by the 1-adrenoceptor antagonist prazosin (0.1 mol/l). Carmoxirole (0.3 mol/l), prazosin (0.1 mol/l) and phentolamine (1 mol/l) totally abolished pressor responses to exogenous noradrenaline (0.05 mol/l). In contrast, quinpirole (0.3 mol/l) did not alter pressor responses to exogenous noradrenaline (0.05 mol/l). Furthermore, carmoxirole (0.003–0.3 mol/l) markedly reduced pressor responses induced by the 1-adrenoceptor agonist methoxamine (1 mol/l) but even the highest concentration of carmoxirole (0.3 mol/l) had no effect on pressor responses induced by bolus injections of either neuropeptide Y (1.5 ng) or angiotensin II (1 ng). Phentolamine (1 mol/l) by itself markedly enhanced S-1 outflow of radioactivity and pressor responses to RNS were virtually unchanged. In the presence of phentolamine carmoxirole (0.03 and 0.3 mol/l) and quinpirole inhibited S-I outflow of radioactivity and pressor responses to RNS. Phentolamine resistant pressor responses to RNS were also inhibited by the P2X-receptor desensitizing agent , -methylene adenosine triphosphate (mATP, 1 mol/l), which by itself in the presence of phentolamine did not alter S-I outflow of radioactivity. The inhibitory effects of carmoxirole (0.3 mol/l) in the presence of phentolame (1mol/l) were antagonized by S(–)-sulpiride (10 mol/l). The data suggest that activation of prejunctional DA2-receptors by quinpirole inhibits noradrenaline release and thereby reduces pressor response to RNS at 1 Hz in rat isolated kidney. Carmoxirole activates prejunctional inhibitory DA2-receptors, but this effect is masked by simultaneous blockade of inhibitory prejunctional -adrenoceptors. Pressor responses to RNS at 1 Hz in rat isolated kidney are largely due to neuronally released noradrenaline whereas phentolamine resistant pressor responses to RNS at 1 Hz are most likely due to ATP, which is co-released with noradrenaline. Carmoxirole inhibits pressor responses to RNS at 1 Hz as well as pressor responses induced by either exogenous noradrenaline or methoxamine by blocking postjunctional 1-adrenoceptors. In addition carmoxirole and quinpirole seem to block phentolamine resistant pressor responses by inhibiting ATP release through activation of prejunctional DA2-receptors. Send offprint requests to L. C. Rump at the above address  相似文献   

4.
The antinociception induced by -endorphin given supraspinally has been previously demonstrated to be mediated by the stimulation of -, but not -, - or -opioid receptors in rats and mice. The present study was designed to determine what types of opioid receptors in the spinal cord are involved in the antinociception induced by intrathecally (i.t.) administered -endorphin. Antinociception was assessed by the tailflick test in male Sprague-Dawley rats. CTOP (0.9–6.6 nmol), a selective -opioid receptor antagonist, or nor-BNI(13.6–95.3 nmol), a selective -opioid receptor antagonist, given i.t. dose-dependently reversed i.t. administered -endorphin-induced inhibition of the tail-flick response. On the other hand, naltrindole (6.6–44.4 nmol), a selective -opioid receptor antagonist, or -endorphin (1–27) (1–6.7 nmol), a selective -opioid receptor antagonist given i.t., did not antagonize the inhibition of the tail-flick response induced by i.t. administered -endorphin. The results are consistent with the previous study in mice [Tseng LF and Collins KA (1992) Eur J Pharmacol 214: 59–65] that the antinociception induced by -endorphin given i.t. is mediated by the stimulation of - and -, but not - and -opioid receptors.Abbreviations i.t. Intrathecal - CTOP D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH2 - nor-BNI Norbinaltorphimine  相似文献   

5.
Summary The involvement of 1- and 2-adrenoceptors in catecholamine-evoked arrhythmias was investigated in isolated human right atrial appendages obtained from 22 patients chronically treated with blockers (usually 1-selective) and 9 patients not treated with blockers. A simple experimental model that assesses the incidence of arrhythmic contractions as a function of heart rate (pacing) is introduced. 1-adrenoceptors were activated by (–)-noradrenaline during 2-adrenoceptor blockade with 50 nmol/l ICI 118551. 2-adrenoceptors were activated by (–)-adrenaline during 1-adrenoceptor blockade with 300 nmol/l CGP 20712A. Both (–)noradrenaline and (–)-adrenaline caused arrhythmic contractions whose incidence was greater at low than at high pacing rates. CGP 20712A (300 nmol/l) blocked the (–)-noradrenaline-evoked contractions in 1/1 atrial strip from 1/1 patient not treated with a blocker and 17/17 atrial strips from 15/15 patients chronically treated with blockers. ICI 118551 (50 nmol/l) blocked the (–)-adrenaline-evoked contractions in 3/4 atrial strips from 3/4 patients not treated with blockers and 17/20 atrial strips from 15/18 patients chronically treated with blockers. The incidence of arrhythmic contractions evoked by both (–)-noradrenaline and (–)-adrenaline was higher in chronically blocked patients than in non blocked patients. We conclude that both 1- and 2-adrenoceptors mediate atrial arrhythmias and that the generation of these arrhythmias is facilitated by chronic 1-adrenoceptor blockade. Correspondence to: A. J. Kaumann at the Clinical Pharmacology Unit, University of Cambridge, as above  相似文献   

6.
The hemolytic activity of -cyclodextrin (-CyD) on rabbit erythrocytes was reduced by the introduction of negatively-charged groups onto the hydroxyls of -CyD; the membrane disrupting abilities decreased in the order of -CyD > 2-hydroxypropyl--CyD (HP--CyD) > sulfobutyl--CyD (SB--CyD) >> -CyD sulfate (S--CyD). Under pre-hemolytic concentrations, both -CyD and SB--CyD induced shape changes of membrane invagination on the erythrocytes. In sharp contrast, S--CyD showed biphasic effect on the shape of the erythrocytes; i.e. the crenation at relatively low concentrations and the invagination at higher concentrations. The S--CyD-induced membrane crenation arose from a direct action on the membranes rather than cell metabolism-mediated effects. Unlike -CyD, S--CyD was found to bind to the erythrocytes and may be confined to the outer surface of the membrane bilayer, which may expand the exterior layer relative to the cytoplasmic half, thereby inducing the cells to crenate. On the other hand, the membrane invagination mediated by the three - CyDs was initiated by extracting specific membrane lipids from the cells, depending upon their inclusion abilities, subsequently leading to the lysis of the cells. These results indicate that SB--CyD and S--CyD interact with the erythrocyte membranes in a differential manner and possess lower membrane disrupting abilities than the parent -CyD and HP--CyD.  相似文献   

7.
Summary The present study investigated the effects of SK&F 104078 (6-chloro-9-[(3-methyl-2-butenyl)oxy]-3methyl-1H,2,3,4,-tetrahydro-3-benzazapine) at pre- and post functional 2-adrenoceptors in the human isolated saphenous vein. Noradrenaline (0.001–100 mol/l) produced concentration-dependent contractions of the human saphenous vein which were competitively antagonised by the 1-adrenoceptor antagonist prazosin (0.01–1.0 mol/l) and the 2-adrenoceptor antagonist, rauwolscine (0.01–1.0 mol/l), indicating the presence of both post functional 1- and 2-adrenoceptors in this preparation. The selective 2-adrenoceptor agonist, UK-14,304 (0.01–100 mol/l) also produced concentration-dependent contractions of the human saphenous vein which were antagonised by both rauwolscine (0.1 mol/l) and prazosin (0.1 mol/l). In the presence of angiotensin II (0.05 mol/l), which itself produced a transient contraction, rauwolscine (0.1 mol/l) produced a rightward shift of the UK-14,304 concentration-response curve while prazosin (0.1 mol/l) had no effect. SK&F 104078 (10.0 mol/l) under these conditions also produced a rightward shift of the concentration-response curve to UK-14,304, but was at least 100-fold less potent than rauwolscine. At pre functional 2-adrenoceptors, exogenous noradrenaline (0.01 and 0.1 gmol/l) induced a concentration-dependent inhibition of stimulation-evoked [7-3H]-noradrenaline release from the human saphenous vein in vitro, which was antagonised by rauwolscine (0:1 mol/l) and tolazoline (10.0 mol/l) but not by SK&F 104078 (10.0 gmol/l).Rauwolscine (0.1 mol/l) produced a small increase in stimulation-evoked [7-3H]-noradrenaline release while both tolazoline and SK&F 104078 failed to produce any enhancement in release in the absence of exogenous agonist atconcentrationsupto10 gmol/l.Insummary, noradrenaline and UK-14,304 contracted the human isolated saphenous vein by an action at both postfunctional 1- and 2-adrenoceptors. These data demonstrate that SK&F 104078 discriminates between post- and pre-junctional 2-adrenoceptors in the human isolated saphenous vein. Send offprint requests to M. V. Sennitt at the above address  相似文献   

8.
Summary The effect of the -adrenoceptor agonist isoprenaline on the plasma concentrations of -endorphin (-E) and -lipotropin (-LPH) was investigated in conscious rats. Isoprenaline (i.m.) elevated plasma -endorphin-like immunoreactivity (-EI) as measured by radioimmunoassay of unextracted plasma, with peak values 24 min after drug administration. This effect was dose-dependent. The lowest effective dose of isoprenaline was 15 g kg–1; 240 g kg–1 exerted a maximum effect, raising plasma -EI about ten-fold above control values. Plasma vasopressin concentrations also increased in response to isoprenaline following a timecourse identical to that of plasma -EI. (±)-Propranolol (1 mg kg–1) but not phentolamine (10 mg kg–1) rendered isoprenaline (240 g kg–1) injections almost ineffective. Because of the cross-reactivity of -LPH in the radioimmunoassay used, plasma was extracted by means of a cation exchange resin and subjected to gel chromatography on a Sephadex G-50 column, avoiding artefactual degradation of the peptides. In isoprenaline-treated rats about 50% of the -EI behaved similar to human -LPH, whereas 45% co-migrated with human -E; immunoreactivity corresponding to -LPH or -E comprised about 70% or 30%, respectively, in the plasma extract of vehicle-treated rats. Dexamethasone pretreatment reduced the isoprenaline-induced increase in plasma -EI by 87%, but left the simultaneous elevation of plasma vasopressin concentrations unchanged.These data demonstrate that isoprenaline stimulates -LPH and -E release in vivo. The possibility of an interrelationship between vasopressin and -E release is discussed.  相似文献   

9.
Platelets of healthy human subjects were incubated with 5-hydroxytryptamine (5-HT) followed by a second incubation with either -endorphin (-end) or the combination of -end and naloxone. -End (300 pg/ml) reduced the levels of 5-HT to 50% of initial values within 15–40 min. After 40–80 min incubation, the levels of 5-HT decreased to approximately zero. Addition of increasing amounts of -end (up to 300 pg/ml) produced increasing releases of 5-HT with increasing doses of -end. The response was dose-related, however variable, across subjects. Addition of either 28.7 or 57.4 pg naloxone to 300 pg -end did not antagonize the effects of -end on 5-HT.  相似文献   

10.
Endplate preparations of the rat left hemidiaphragm were incubated with [3H]choline to label neuronal transmitter stores. Nerve evoked release of newly-synthesized [3H]acetylcholine was measured in the absence of cholinesterase inhibitors to investigate whether snake venom neurotoxins by blocking presynaptic nicotinic autoreceptors affect evoked transmitter release. Contractions of the indirectly stimulated hemidiaphragm were recorded to characterize the blocking effect of -neurotoxins at the postsynaptic nicotinic receptors.Neither the long chain neurotoxins -cobratoxin (1 g ml–1) and -bungarotoxin (5 g ml–1) nor the short chain neurotoxin erabutoxin-b (0.1, 1 and 10 gml–1) affected the nerve-evoked release of [3H]acetylcholine. -Bungarotoxin (1 and 5 g ml–1), a toxin preferentially blocking neuronal nicotinic receptors, did also not affect evoked [3H]acetylcholine release, whereas (+)-tubocurarine (1 M) under identical conditions reduced the release by about 50%. -Bungarotoxin, -cobratoxin and erabutoxin-b concentration-dependently (0.01–0.6 g ml–1)inhibited nerve-evoked contractions of the hemidiaphragm. All neurotoxins except erabutoxin-b enhanced the basal tritium efflux immediately when applied to the endplate preparation or to a non-innervated muscle strip labelled with [3H]choline. This effect was attributed to an enhanced efflux of [3H]phosphorylcholine, whereas the efflux of [3H]choline and [3H]acetylcholine was not affected.It is concluded that the -neurotoxins and -bungarotoxin do not block presynaptic nicotinic receptors of motor nerves. These nicotinic autoreceptors differ from nicotinic receptors localized at the muscle membrane and at autonomic ganglia.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号