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1.
G. D'Agostino M. C. Chiari E. Grana 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(1):76-81
Summary The inhibitory effects of some muscarinic agonists on tritiated acetylcholine release evoked by field stimulation were investigated in the rat urinary bladder strip. The acetylcholine stores of the preparation were labelled with 3H-choline. Electrical field stimulation caused an outflow of tritium, reflecting the release of 3H-acetylcholine. The release of 3H-acetylcholine was decreased in a concentration-dependent manner by all the agonists tested: oxotremorine, muscarone, muscarine, carbachol and methylfurtrethonium. On the contrary, only muscarine and muscarone enhanced the basal efflux of tritium in a concentration-dependent fashion. Concentration-response curves were determined both at 2 Hz and at 1 Hz by using intermittent administration of the drugs. Maximal depression in release (by 78 – 82%) was observed in experiments at 1 Hz. A similar inhibition was obtained at 2 Hz frequency only when a low concentration of calcium (0.6 mM) in the medium was used. Oxotremorine was the most potent among the tested compounds with the same intrinsic activity as the other drugs. In contrast to the other agonists investigated, oxotremorine showed in about 10-fold greater potency at pre- than at postjunctional muscarine receptors in the rat urinary bladder. This difference might depend either on heterogeneity of muscarine receptors or on different mechanism(s) relating to the transducing properties of receptors at the pre- and postjunctional level. A comparison between the relative prejunctional potencies in the rat urinary bladder and in the guinea pig myenteric plexus (data from the literature) suggests that prejunctional muscarine receptors are similar in these tissues. Furthermore, the findings obtained with a low concentration of calcium in the medium may support the view that intraneuronal availability of calcium plays a significant role in modulating the prejunctional negative feed-back mechanism in the rat urinary bladder.Send offprint requests to Dr. G. D'Agostino at the above address 相似文献
2.
Lorenzo Beani Clementina Bianchi Lena Nilsson Agneta Nordberg Luciana Romanelli Lucia Sivilotti 《Naunyn-Schmiedeberg's archives of pharmacology》1985,331(2-3):293-296
Summary Nicotine 1.8×10–5–1.8×10–4 mol/l enhanced the spontaneous3H-efflux from guinea-pig cortical slices preloaded with3H-choline and perfused in the presence of hemicholinium (HC-3).The facilitation of tritium outflow was prevented by tetrodotoxin 5×10–7 mol/l and byd-tubocurarine 4.5×10–6 mol/l. Nicotine 1.8×10–6–1.8×10–4 mol/l, and the agonist cytisine 5×10–7–5×10–5 mol/l increased, in a concentration-dependent way,3H-efflux from electrically-stimulated slices (0.2 Hz). The concentration-response curves of both drugs were parallelly shifted to the right byd-tubocurarine 4.5×10–6 mol/l. The EC50 values (i.e. the concentrations required to cause a 50% increase in the S2/S1 ratio) changed for nicotine from 5.58×10–5 to 4.34×10–4 and for cytisine from 6.3×10–6 to 2.75×10–4 mol/l in the absence and in the presence of the antagonist, respectively.In the range of 0.2–2 Hz the magnitude of the effect of nicotine was inversely related to the rate of stimulation.The response to nicotine was subject to rapidly developing tachyphylaxis; it was resistant to atropine.It is concluded that nicotine and cytisine facilitate3H-efflux from the cholinergic nerve endings of guinea-pig cerebral cortex. This effect involves sodium-dependent mechanisms and is due to an interaction of the drugs with receptors showing affinity ford-tubocurarine. 相似文献
3.
Torsten Reinheimer Eva Harnack Kurt Racke Ignaz Wessler 《British journal of pharmacology》1998,125(2):271-276
- The release of neuronal [3H]acetylcholine (ACh) from isolated human bronchi after labelling with [3H]choline was measured to investigate the effects of prostanoids.
- A first period of electrical field stimulation (S1) caused a [3H]ACh release of 320±70 and 200±40 Becquerel (Bq) g−1 in epithelium-denuded and epithelium-containing bronchi respectively (P>0.05). Subsequent periods of electrical stimulation (Sn, n=2, 3, and 4) released less [3H]ACh, i.e. decreasing Sn/S1 values were obtained (0.76±0.09, 0.68±0.07 and 0.40±0.04, respectively).
- Cumulative concentrations (1–1000 nM) of EP-receptor agonists like prostaglandin E2, nocloprost, and sulprostone (EP1 and EP3 selective) inhibited evoked [3H]ACh release in a concentration dependent manner with IC50 values between 4–14 nM and maximal inhibition of about 70%.
- The inhibition of evoked [3H]ACh release by prostaglandin E2, nocloprost and sulprostone was not affected by the DP-, EP1- and EP2-receptor antagonist AH6809 at a concentration of 3 μM, i.e. a 3–30 times greater concentration than its affinity (pA2 values) at the respective receptors.
- Circaprost (IP-receptor agonist; 1–100 nM), iloprost (IP- and EP1-receptor agonist; 10-1000 nM) and U-46619 (TP-receptor agonist; 100–1000 nM) did not significantly affect [3H]ACh release.
- Blockade of cyclooxygenase by 3 μM indomethacin did not significantly modulate evoked [3H]ACh release in epithelium-containing and epithelium-denuded bronchi. Likewise, the combined cyclo- and lipoxygenase inhibitor BW-755C (20 μM) did not affect evoked [3H]ACh release.
- In conclusion, applied prostanoids appear to inhibit [3H]ACh release in epithelium-denuded human bronchi under the present in vitro conditions, most likely via prejunctional prostanoid receptors of the EP3 subtype.
4.
Preferential release of newly synthesized 3H-acetylcholine from rat cerebral cortex slices in vitro 总被引:1,自引:0,他引:1 下载免费PDF全文
1. Slices of rat cerebral cortex after treatment with the irreversible cholinesterase inhibitor soman, were incubated for 5 min in a Krebs-Henseleit solution containing 25 mM KCl and (3)H-choline. Subsequently incubation was continued in a medium containing non-radioactive choline and this medium was replaced at 5 min intervals. The amounts of labelled and total acetylcholine (ACh) released into the medium and extracted from the slices were determined at intervals.2. After the initial 5 min contact with (3)H-choline, 44% of the newly synthesized ACh contained a choline moiety originating from the choline in the medium. During the initial 5 min and the subsequent incubation part of the labelled ACh was released. While the rate of total ACh release remained constant, that of the release of labelled ACh was highest in the 5 min period following the initial incubation with (3)H-choline and then declined exponentially.3. The ratio of labelled ACh/total ACh in the ACh released during the initial 5 min incubation with (3)H-choline and during the subsequent 5 min was about three times as high as that in the ACh extracted from the slices at the end of these incubation periods.4. The ratio of labelled ACh/total ACh in superficial layers of the slices was not higher than that in the total slices.5. The rates of release of labelled and unlabelled ACh decreased when calcium was omitted from the incubation medium and were restored when the calcium was added. This suggests that both labelled and unlabelled ACh were released from nerve endings. The efflux of (3)H-choline was not calcium dependent.6. It is concluded that labelled ACh newly synthesized from externally applied (3)H-choline does not exchange immediately with all other ACh in the tissue and has a greater chance of being released than unlabelled ACh. 相似文献
5.
The guinea-pig ileum longitudinal muscle-myenteric plexus preparation, preincubated with 3H-choline or 3H-noradrenaline, was mounted in an organ bath and superfused with Tyrode's solution. Alaproclate (2-(4-chlorophenyl)-1,1-dimethyl 2-aminopropanoate) (0.01-0.5 mmol/l) reduced (IC50 = 0.1 mmol/l) and at about 0.5 mmol/l completely blocked the electrically evoked 3H-acetylcholine secretion. The depressing effect of alaproclate (0.2 mmol/l) was not counteracted by atropine (0.01, 1 or 10 mumol/l), hexamethonium (0.1 mmol/l), phentolamine (1 mumol/l) yohimbine (1 mumol/l), haloperidol (1 mumol/l), 8-phenyltheophylline (10 mumol/l), cyproheptadine (1 mumol/l), metitepine (1 mumol/l), bicuculline (10 mumol/l), picrotoxinin (0.1 mmol/l), forskolin (25 mumol/l), 3-isobutyl-1-methylxanthine (5 mmol/l), nifedipine (1 mumol/l), verapamil (1 mumol/l), dilitiazem (1 mumol/l), high calcium (6 mmol/l), high potassium (10 or 15 mmol/l), tetraethylammonium (2 mmol/l), 4-aminopyridine (0.5 mmol/l), apamin (0.5 mumol/l), barium (0.5 mmol/l) or quinine (0.1 mmol/l). Among the potassium channel blockers tested only quinine (at 0.5 or 1 mmol/l), in the same manner as lidocaine, reduced the evoked secretion of 3H-acetylcholine. The results are in agreement with the hypothesis that the effect of alaproclate on the evoked 3H-acetylcholine secretion is not mediated by a neurotransmitter receptor, or a potassium channel sensitive to tetraethylammonium, 4-aminopyridine, apamin, or barium or quinine, but is due to a local anaesthetic effect. In contrast to the evoked secretion, the spontaneous release of 3H-acetylcholine was enhanced by high concentrations of alaproclate (0.4-1 mmol/l). The mechanism underlying the effect of alaproclate on the spontaneous release remains to be established. Alaproclate (0.25 or 0.5 mmol/l) also enhanced the spontaneous release and reduced the electrically evoked 3H-noradrenaline secretion. 相似文献
6.
In the isolated rat heart perfused with Krebs solution and prelabeled with [3H]noradrenaline, we examined the effect of prostaglandins (PG) I2, E2, 6-keto-PGF1α and their precursor, arachidonic acid, on the overflow of tritium elicited by potassium (K+) and by stimulation of cardiac sympathetic nerve plexus. Prostaglandins E2, I2 and arachidonic acid but not 6-keto-PGF1α reduced K+ and nerve stimulation-induced overflow of tritium. Administration of indomethacin, an inhibitor of cyclooxygenase, increased tritium overflow elicited by either K+ or by nerve stimulation. During infusion of indomethacin, the inhibitory effect of both PGE2 and PGI2 on the K+ or nerve stimulation-induced overflow of tritium remained unaltered. In contrast, the effect of arachidonic acid to reduce K+ or nerve stimulation-induced overflow of tritium was abolished by indomethacin, indicating that the fatty acid inhibits release of tritium by its conversion to a product(s) of cyclooxygenase, presumably PGI2 and PGE2. These data suggest that prostaglandins, particularly PGI2 and PGE2 sythesized in the isolated rat heart act on prejunctional sites to modulate release of the adrenergic transmitter. 相似文献
7.
8.
Summary At temperatures from 15–25° C perfused rat livers take up potassium from the perfusion medium or release small amounts of the cation. Both increasing or decreasing temperature enhance the K+-release in the absence as well as in the presence of red cells. Two possible explanations of this phenomenon, hypoxia and phase-transition of the plasma membrane, are discussed.This work is supported by the Deutsche Forschungsgemeinschaft. 相似文献
9.
《Toxicology letters》1998,99(3):169-173
Effects of soman on N-methyl-d-aspartate (NMDA) evoked [3H]norepinephrine (NE) release were examined in rat brain cortical slices. NMDA increased [3H]NE release in a concentration-dependent manner. Soman could inhibit the increase evoked by NMDA, but carbachol, an agonist of cholinergic receptor, could potentiate the increase evoked by NMDA. Atropine (a selective muscarinic antagonist) attenuated the release of [3H]NE induced by NMDA in the presence of carbachol or acetylcholine (ACh), but had no effect on the release of [3H]NE induced by NMDA alone. Both d-tubocurarine (an antagonist of nicotinic receptor) and atropine had no effect on the release of [3H]NE induced by NMDA in the presence of soman. These results suggested that soman has a direct action at non-cholinergic sites, probably at NMDA receptors. 相似文献
10.
BACKGROUND AND PURPOSE: Nicotinic agonists increase sympathetic field-stimulus-evoked contraction of the rodent vas deferens, presumably by increasing evoked neurotransmitter release. This presumption was tested in two species. EXPERIMENTAL APPROACH: The effect of the nicotinic acetylcholine receptor (nAChR) agonist epibatidine on neurotransmitter release in mouse and guinea pig isolated vas deferens was investigated using contraction studies and conventional intracellular recording techniques. KEY RESULTS: In 12 of 14 mouse vasa deferentia, slow bath application of epibatidine (100 nM) had no significant effect on excitatory junction potential (EJP) amplitude and spontaneous EJP (SEJP) frequency. However, rapid application of epibatidine to the mouse vas deferens caused an increase in SEJP frequency (by 530%), with no effect on EJP amplitude. Despite the absence of an effect on EJPs, electrically-evoked contractions of the mouse vas deferens were significantly increased in the presence of epibatidine (by 50%). A transient contraction was reliably induced by a higher epibatidine concentration (1 microM). This contraction was significantly reduced in the presence of prazosin, tetrodotoxin, or alpha,beta-methyleneATP. Epibatidine did not induce a contraction in the presence of a combination of prazosin, alpha,beta-methyleneATP and cyclopentolate. In guinea pig vasa deferentia, bath-applied epibatidine potentiated EJP amplitude in a biphasic pattern, lasting for at least 30 minutes. CONCLUSION AND IMPLICATIONS: The nAChR-mediated augmentation of neurogenic contraction is indeed prejunctional, but in the mouse arises from an increase in spontaneous neurotransmitter release that primes smooth muscle for subsequent contraction, while in the guinea pig there is a direct augmentation of evoked neurotransmitter (ATP) release. 相似文献
11.
The present study was designed to investigate the effect of naloxone, a well known opioid antagonist, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal glands, and to establish its mechanism of action. Naloxone (10(-6) approximately 10(-5) M), perfused into an adrenal vein for 60 min, produced dose- and time-dependent inhibition of CA secretory responses evoked by ACh (5.32 x 10(-3) M), high K+ (5.6 x 10(-2) M), DMPP (10(-4) M) and McN-A-343 (10(-4) M). Naloxone itself also failed to affect the basal CA output. In adrenal glands loaded with naloxone (3 x 10(-6) M), the CA secretory responses evoked by Bay-K-8644, an activator of L-type Ca2+ channels, and cyclopiazonic acid, an inhibitor of cytoplasmic Ca(2+)-ATPase, were also inhibited. In the presence of met-enkephalin (5 x 10(-6) M), a well known opioid agonist, the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly inhibited. Taken together, these results suggest that naloxone greatly inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as that by membrane depolarization. It seems that these inhibitory effects of naloxone does not involve opioid receptors, but might be mediated by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of Ca2+ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself. 相似文献
12.
H. Fuder R. Siebenborn E. Muscholl 《Naunyn-Schmiedeberg's archives of pharmacology》1982,318(4):301-307
Summary Isolated rat hearts with the right sympathetic nerves attached were perfused at a constant flow rate of 7 ml/min with Tyrode's solution. (-)-3H-Noradrenaline (final concentration 10–13.9 nM) was infused for 10 min to label the noradrenaline stores. After wash-out the sympathetic nerves were stimulated electrically (3 Hz, 180 impulses, 1 ms, 20–30 mA) three times (S1–S3) at intervals of 15 min. 3H-Noradrenaline and its metabolites were determined by liquid scintillation counting according to Graefe et al. (1973).Both, nicotine 50 M and p-aminophenethyltrimethylammonium (PAPETA) 30 M, enhanced the 3H-noradrenaline overflow in the absence of nerve stimulation. The effect of PAPETA was biphasic and was still observed in the presence of N-methylatropine 0.1 M. Hexamethonium 10 M abolished the first phase only, but cocaine 10 M antagonized both phases.The decline of the stimulation-evoked overflow of 3H-noradrenaline from the first to the third stimulation period was similar in the absence and in the presence of cocaine 10 M starting before S1 and perfused throughout. Cocaine 10 M added before S2, however, enhanced the evoked overflow by 77%.PAPETA 30 M increased the stimulation-evoked overflow by 67% in the absence, and by 73% of the respective control in the presence, of hexamethonium 10 M. PAPETA 30 M failed to enhance the evoked overflow in the presence of cocaine. Hexamethonium (added before S2) did not modify the effectiveness of nerve stimulation.Nicotine, neither when perfused from 6 min before S2, nor when added to the perfusion fluid simultaneously with the onset of nerve stimulation, caused changes in the 3H-noradrenaline output upon S2.Upon stimulation a rather discrete increase in 3H-DOPEG overflow was observed. This increase was abolished by cocaine and/or PAPETA.It is concluded that nicotine and PAPETA stimulate the output of 3H-noradrenaline from the rat heart sympathetic nerves by activation of nicotine receptors. However, the amount of transmitter released is small. Neither drug appeared to modulate the output of 3H-noradrenaline upon electrical nerve stimulation via nicotine receptors.PAPETA, like cocaine, appears to block the reuptake of released transmittsrs thereby enhancing the 3H-noradrenaline overflow and reducing the overflow of 3H-DOPEG (formed intraneuronally from recaptured noradrenaline after nerve stimulation).Abbreviations used DOMA
3,4-dihydroxymandelic acid
- DOPEG
3,4-dihydroxyphenylglycol
- MOPEG
3-methoxy-4-hydroxy-phenylglycol
- NA
noradrenaline
- NMN
normetanephrine
- OMDA
O-methylated deaminated metabolites (sum of MOPEG and VMA)
- PAPETA
p-aminophenethyltrimethylammonium
- VMA
3-methoxy-4-hydroxymandelic acid 相似文献
13.
Naline E Höglund CO Vincent F Emonds-Alt X Lagente V Advenier C Frossard N 《European journal of pharmacology》2007,560(2-3):206-211
The nerve growth factor (NGF) is a neurotrophic factor essential for the development and survival of neurons. It has also been identified as a mediator of inflammation and can cause airway hyperresponsiveness [Frossard et al., Eur. J. Pharmacol. 500, 453 (2004)]. Evidence in rodents suggests a link between tachykinins, the sensory nerves, and NGF. Recent evidence shows that NGF is released by the proinflammatory cytokine interleukin-1β and induces hyperresponsiveness to the tachykinin NK1 receptor agonist [Sar9,Met(O2)11]SP in isolated human bronchi. The aim of this study was to determine the role of sensory nerves through the effect of the tachykinin NK3 receptor antagonist SR142801 in the interleukin-1β effects and/or the NGF-induced airway hyperresponsiveness. SR142801 (0.1 μM) abolished the interleukin-1β (10 ng/ml, 21 °C, 15 h)-induced increased NGF release from isolated human bronchi in vitro (P < 0.05). In organ bath studies, SR142801 also abolished the interleukin-1β-induced airway hyperresponsiveness to [Sar9,Met(O2)11]SP (0.1 μM) (P < 0.05). SR142801 also inhibited the NGF-induced airway hyperresponsiveness (P < 0.01). This study suggests tachykininergic sensory nerves to be involved in the interleukin-1β-induced NGF release and airway hyperresponsiveness. 相似文献
14.
Decreased sensory neuropeptide release in isolated bronchi of rats with cisplatin-induced neuropathy
Horvath P Szilvassy J Nemeth J Peitl B Szilasi M Szilvassy Z 《European journal of pharmacology》2005,507(1-3):247-252
We studied if attenuated neurogenic bronchoconstriction was associated with a change in sensory neuropeptide release in preparations from rats with cisplatin-induced neuropathy. Electrical field stimulation (100 stimuli, 20 V, 0.1 ms, 20 Hz) induced an increase in the release of somatostatin, calcitonin gene-related peptide (CGRP) and substance P determined by radioimmunoassay from baseline 0.18+/-0.01, 0.17+/-0.01 and 0.86+/-0.02, to 0.59+/-0.02, 1.77+/-0.04 and 5.96 fmol/mg wet tissue weight, respectively, in organ fluid of tracheal tubes from rats. This was significantly attenuated to post-stimulation values of 0.36+/-0.02, 0.45+/-0.02, 4.68+/-0.24 fmol/mg wet tissue weight for somatostatin, CGRP, and substance P, respectively, with a significant decrease in field stimulation-induced contraction of bronchial preparations from animals 11 days after a 5-day treatment period with cisplatin (1.5 mg/kg i.p. once a day). The cisplatin-treated animals developed sensory neuropathy characterized by a 40% decrease in femoral nerve conduction velocity. The results show that a decrease in tracheo-bronchial sensory neuropeptide release associates with feeble bronchomotor responses in rats with cisplatin-induced sensory neuropathy. 相似文献
15.
Pre-junctional effects of oximes on [3H]-acetylcholine release in rat hippocampal slices during soman intoxication 总被引:2,自引:0,他引:2
In this study, the non-reactivating effects of oximes in the hippocampus of the rat are investigated. The potassium (51 mM) evoked release of [(3)H]-acetylcholine and the liberation of [(3)H]-choline were determined in hippocampal slices following in vitro exposure to soman and five oximes (toxogonin, HI-6, HL?-7, P2S and 2-PAM) in separate experiments by superfusion. In the absence of soman, toxogonin and HL?-7 in particular induced a concentration dependent significant increase in the evoked release of [(3)H]-acetylcholine. There was also a significant effect of HI-6, but the effect was much smaller. Two pralidoxime salts, P2S (methanesulfonate salt) and 2-PAM (methiodide salt), had similar but lower effects that were only observed at relatively high concentrations. Experiments performed following complete inhibition of the acetylcholinesterase activity by soman (1.0 microM) showed that HI-6 and HL?-7 induced a significant decrease in the potassium-evoked release of [(3)H]-acetylcholine, while the liberation of [(3)H]-choline increased. Toxogonin, P2S and 2-PAM did not reduce significantly the evoked release of [(3)H]-acetylcholine. Only limited reactivation of the acetylcholinesterase activity was observed in superfusion experiments with toxogonin, HI-6, P2S and 2-PAM following exposure of hippocampal slices to soman. However, HL?-7 was proved to be relatively more effective in reactivating the acetylcholinesterase activity at high concentrations (50 and 200 microM). The acetylcholinesterase activity was reactivated to approximately 12% and 40% of control, respectively. It is concluded that HI-6 and HL?-7 have important non-acetylcholinesterase reactivating properties following soman poisoning, as may be seen by the significant reduction in the evoked release of [(3)H]-acetylcholine effected by these oximes. HL?-7 is of particular interest in view of its ability to additionally improve reactivation of the acetylcholinesterase activity. 相似文献
16.
K. Racke B. Hering U. Hochgesand 《Naunyn-Schmiedeberg's archives of pharmacology》1988,337(3):301-307
Summary Isolated neural lobes of the rat pituitary gland were fixed by their stalks to a platinum wire electrode. They were loaded with 45calcium and then superfused with radioactivity-free Krebs-solution. The efflux of 45calcium into the superfusion medium was determined. After 54–60 min of superfusion the spontaneous outflow of 45calcium was 2.03%/min of the tissue 45calcium. It was not affected by cadmium (Cd2+, 0.03-3 mmol/1), but reduced by 40% in the presence of 1 mmol/1 gadolinium (Gd3). Electrical stimulation with pulses of 15 Hz (3 times for 1 min with intervals of 1 min) evoked a 45calcium release of 14.4% of the tissue radioactivity. The evoked release of 45calcium was reduced by 80% in the presence of tetrodotoxin and by about 50% in the presence of gallopamil (D600, 30 ol/l) or after omission of unlabelled calcium from the superfusion medium. Gd3+ concentration-dependently reduced the evoked release by maximally 75% at 3 mmol/l. However, it inhibited the evoked release of 45calcium less effectively than the release of vasopressin evoked by identical stimulation conditions. Cd2+ reduced the evoked release by maximally 55% at 300 mol/l. The effect of Cd2+ on the evoked release of vasopressin was not tested because Cd2+ markedly increased the spontaneous outflow of vasopressin. When the stimulation was carried out for only 1 min at 15 Hz (i. e. 900 pulses) the evoked release of 45calcium was 10.6% of the tissue 45calcium and 100 mol/l Cd2+ or 300 mol/l Gd3+ caused a reduction of the evoked release similar to that observed when 3 periods of stimulation were applied. However, when 900 pulses were applied at a frequency of 3 Hz the evoked release of 45calcium was only 4.4% and was not affected by 100 gmol/l Cd2+ or 300 mol/l Gd3+. In previous experiments, the release of vasopressin and oxytocin evoked by 900 pulses at 3 Hz amounted to only about 10% of the hormone release evoked by 900 pulses at 15 Hz. In conclusion, electrical stimulation of the rat pituitary stalk increases the efflux of 45calcium from neurohypophyses loaded with 45calcium. Only part of the evoked release of 45calcium appears to be associated directly with the stimulus-secretion coupling.Abbreviations Gd3+
gadolinium
- Cd2+
Cadmium
Send offprint requests to K. Racké 相似文献
17.
Summary The isolated perfused pancreas obtained from rats treated with thyroxine (600 g/kg/day, for five days) showed a modified insulin secretory pattern. Glucose (300 mg/100 ml) induced a higher first peak of insulin secretion which appeared slightly faster than in controls. The delayed second peak, as induced by glucose in the normal rat pancreas was absent after thyroxine treatment. Tolbutamide (20 mg/100 ml) yielded a slightly higher first peak followed by a moderately increased basal insulin secretion in the treated group. 相似文献
18.
Summary Dopamine evokes calcium-dependent release of 3H-acetylcholine from superfused rabbit retina labeled in vitro with 3H-choline, through activation of a D-1 dopamine receptor. This study investigates the activation of this receptor by endogenous dopamine and the modulation of the spontaneous and dopamine-evoked release of 3H-acetylcholine from rabbit retina labeled with 3H-choline by GABAergic agonists and antagonists. Endogenous dopamine, released from dopaminergic amacrine neurons by the indirect amines tyramine or D-amphetamine evoked the calcium-dependent release of 3H-acetylcholine from rabbit retina. The release of 3H-acetylcholine elicited by tyramine (10 M) or D-amphetamine (10 M) was attenuated by the selective D-1 antagonist SCH 23390 (0.1 M) and by the dopamine uptake inhibitor nomifensine (3 M). At concentrations of 1 mM and 1 M respectively, GABA and muscimol inhibited the spontaneous release of tritium from rabbit retina labeled in vitro with 3H-choline. Picrotoxin and bicuculline (10 M) increased the spontaneous release of tritium. GABA and the GABA agonist muscimol (0.01–100 M) inhibited in a concentration-dependent manner the release of 3H-acetylcholine elicited by 100 M dopamine with IC50 values of 4.5 M and 0.02 M respectively. The inhibition of dopamine-evoked 3H-acetylcholine release by GABA (10 M) and muscimol (0.1 M) was antagonized by the GABA antagonists bicuculline and picrotoxin. Picrotoxin and bicuculline (10 M) increased the spontaneous release of tritium, and potentiated the release of 3H-acetylcholine evoked by 100 M dopamine consistant with a tonic, inhibitory GABAergic input to the cholinergic amacrine neurons in rabbit retina. Dopamine-evoked acetylcholine release in rabbit retina may be of physiological importance as D-1 dopamine receptor-mediated increases in 3H-acetylcholine release from rabbit retina can be elicited by endogenous dopamine. In addition, activation of GABA receptor sites modulates the spontaneous and dopamine-evoked acetylcholine release from rabbit retina.
Send offprint requests to M. L. Dubocovich at the above address 相似文献
19.
N Grosman 《Agents and actions》1988,25(3-4):284-290
The ability of the flavonoid phloretin to inhibit histamine release from rat mast cells varied considerably with the releasing agent investigated. The response to the combination of the ionophore A23187 and the phorbol ester TPA and to suboptimal concentrations of the ionophore (0.5 microM) was potently inhibited (IC50 about 5 microM), whereas phloretin was less potent against responses to the ionophore (1 microM) (IC50 of 17 microM), to antigen alone and in combination with TPA (IC50 of 30-50 microM), to TPA in the absence of calcium (IC50 of 50 microM) and to compound 48/80 in the absence and presence of calcium (IC50 of 60-90 microM). The inhibition by phloretin at concentrations above 10 microM was partly counteracted by glucose (5 mM) indicating effects on oxidative metabolism. The flavonoid quercetin was equally potent in inhibiting histamine release induced by antigen, the ionophore at different concentrations and in combination with TPA (IC50 of 20 microM). Although not conclusive, the results are consistent with an inhibition of protein kinase C by phloretin at concentrations below 10 microM. At higher concentrations unspecific actions become apparent and phloretin therefore seems to be of limited utility as a probe for signal-pathways in cell responses. 相似文献
20.
The effect of prednisolone and ketotifen on the antigen-induced bronchoconstriction and mediator release in rat isolated lungs. 下载免费PDF全文
Using a new method for inducing IgE-mediated, systemic anaphylaxis in the rat both prednisolone and ketotifen had been shown previously to be effective in suppressing the bronchial anaphylaxis in vivo. In order to study the mode of action underlying their bronchoprotective effect, both agents were also tested on the antigen-induced bronchoconstriction in rat isolated lungs in relation to the mediator release in the lung-effluent. The presence of histamine, 5-hydroxytryptamine (5-HT) and SRS-A could be detected biologically in the lung-effluent during bronchoconstriction. Histamine and 5-HT were determined quantitatively by means of h.p.l.c. with fluorimetric detection, whereas SRS-A was determined using the guinea-pig ileum in a cascade set-up. Although both prednisolone and ketotifen inhibited the antigen-induced bronchoconstriction effectively, it appeared that only prednisolone suppressed the release of histamine, 5-HT and SRS-A in the lung-effluent significantly, whereas ketotifen had no effect. On account of these data it is suggested that the bronchoprotective effect of prednisolone is mainly based on inhibition of the release of the mediators involved, whereas the effect of ketotifen may be based on receptor antagonism. 相似文献