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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using an in vitro rabbit pancreas system, we studied the effect of monoamine oxidase (MAO) inhibitors on flucose-stimulated insulin secretion. We evaluated the effect of both brief (15 min) and prolonged (60 min) exposure of pancreas segments to non-hydrazine (harmine, alpha-methyltryptamine, tranylcypromine and pargyline) and hydrazine (phenelzine, nialamide, iproniazid) type MAO inhibitors. All of the hydrazine type MAO inhibitors potentiated glucose-stimulated insulin secretion. Of the non-hydrazine inhibitors, only harmine and alpha-methyltryptamine potentiated glucose-stimulated insulin secretion. Hydrazine, although not itself an MAO inhibitor, also potentiated insulin secretion. Sixty minutes of exposure to tranylcypromine or alpha-methyltryptamine caused a decrease in insulin secretion. These MAO inhibitors are primary amines and primary amines can inhibit insulin secretion. The dopamine (DA) or serotonin (5-HT) content of the B-cells was increased by incubating rabbit pancreas with L-3, 4-dihydroxyphenylalanine (L-Dopa) or 5-hydroxytryptophan (5-HTP) for forty-five minutes prior to stimulation with glucose. Non-hydrazine MAO inhibitors increased dopamine inhibition of insulin secretion and either did not alter, or decreased serotonin inhibition of insulin secretion. Rabbit pancreatic islets were isolated using the collagenase digestion technique. The MAO activity of islet homogenates was determined using 5-HT and DA as substrates. Rabbit islet MAO has only one-tenth the specific activity against 5-HT (35 +/- 8.7 mumumoles/mg/min, M +/- SEM) that it has against DA (357 +/- 62.3 mumumoles/mg/min). This suggests that one reason that MAT inhibitors do not increase serotonin inhibition of insulin secretion is because MAO is not the major pathway for 5-HT inactivation in rabbit pancreatic islets. These studies suggest that MAO inhibitors alter insulin secretion, by both decreasing B-cell monoamine degradation and by mechanisms that do not involve MAO inhibition.
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PMID:Monoamine oxidase inhibitors: nature of their interaction with rabbit pancreatic islets to alter insluin secretion. 110 23

A number of in vitro effects of melatonin on human platelets were revealed in previous studies. In order to examine whether high affinity binding sites for [3H]-melatonin were present in membrane preparations of human platelets, a rapid filtration procedure through Whatman GFB paper was employed. Maximal melatonin binding was attained within 3 hr at 0 degree C. Scatchard analysis indicated a single population of binding sites with a dissociation constant (Kd) = 4.1 +/- 0.5 nM and maximal number of binding sites (Bmax) = 24.2 +/- 1.9 fmol/mg protein (mean +/- SEM of five experiments). When various indole analogs were tested for their ability to inhibit [3H]-melatonin binding, the following Ki (nM) were obtained: 6-chloromelatonin (11.4), 2-iodomelatonin (22.0), melatonin (24.7), 5-methoxytryptophol (49.9), N-acetylserotonin (68.9), 6-hydroxymelatonin (78.2), 5-methoxytryptamine (184). Serotonin was a potent inhibitor of [3H]-melatonin binding with a Ki = 20.6 nM. Except for 2-methylserotonin and alpha-methylserotonin, a number of serotonin agonists and antagonists tested did not affect melatonin binding to platelet membranes. Binding experiments carried out at either 0800 or 2000 did not reveal time-dependent differences in Kd or Bmax. The results suggest that high affinity melatonin acceptors are present in human platelets.
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PMID:Binding sites for [3H]-melatonin in human platelets. 133 27

The use of 3H-paroxetine as a ligand for quantitative autoradiography of serotonin (5-HT) transport sites was optimized, and the distribution of 3H-paroxetine binding sites in rat brain was studied. Under the conditions described, 3H-paroxetine binding in forebrain sections was of high affinity and saturable, with a Kd of 0.18 +/- 0.02 nM (mean +/- SEM) and Bmax of 268 +/- 12 fmol/mg of protein (n = 3). Nonspecific binding was 10.7% +/- 1.0 of the total binding (n = 8). The distribution of 3H-paroxetine binding sites closely matched the regional distribution of 5-HT nerve terminals and cell bodies. The highest concentrations of 3H-paroxetine binding sites were found in the dorsal raphe nucleus (563 +/- 55 fmol/mg tissue, n = 4), and high densities of binding were also found in the locus coeruleus, medial forebrain bundle, substantia nigra, several limbic structures (amygdala, hippocampus, hypothalamus, olfactory tubercle, septum, and thalamus), and components of the visual relay system (superior colliculus and the lateral geniculate body). Although lesioning of 5-HT neurons with p-chloroamphetamine (PCA) drastically eliminated 3H-paroxetine binding in most regions of the rat brain, significant binding remained in the raphe nuclei and medial forebrain bundle suggesting that 3H-paroxetine binding in these regions was to presynaptic sites on cell bodies or axons relatively resistant to PCA.
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PMID:Quantitative autoradiography of 3H-paroxetine binding sites in rat brain. 142 30

Platelets of healthy smokers and non-smokers were prepared and their content of 5-hydroxytryptamine was determined by HPLC with electrochemical detection. Platelet 5-HT levels in smokers (728 +/- 156 pmol per 10(8) platelets, mean +/- SEM, n = 9) were significantly higher than those in non-smokers (353 +/- 156 pmol per 10(8) platelets, n = 11). Smoking of a single cigarette caused a transient increase in platelet 5-HT levels by about 350% in non-smokers, but had no additional effect in smokers. Similarly, chewing of nicotine gum (4-8 mg nicotine) resulted in a transient increase in platelet 5-HT by about 100% in non-smokers, but not in smokers. In conclusion, smoking of cigarettes can cause an increase in platelet 5-HT, most likely via an enhanced supply of 5-HT from enterochromaffin cells which can be stimulated via nicotine receptors.
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PMID:Effects of cigarette smoking or ingestion of nicotine on platelet 5-hydroxytryptamine (5-HT) levels in smokers and non-smokers. 152 Oct 34

The pharmacological characteristics of the high affinity [3H]5-hydroxytryptamine ([3H]5-HT) uptake system were investigated in the cerebral cortex of the rat and guinea-pig. In crude cortical synaptosomal preparations from the rat and guinea-pig, [3H]5-HT accumulated with high affinity (Km, 72 +/- 12 and 57 +/- 14 nM for rat and guinea-pig cortical synaptosomal preparation, respectively, mean +/- SEM, N = 5) and with a comparable maximum activity (Vmax, 1.22 +/- 0.21 and 0.90 +/- 0.19 pmol/min/mg protein for rat and guinea-pig cortical synaptosomal preparation, respectively, mean +/- SEM, N = 5). Competition studies employing a range of structurally diverse competing compounds showed that the [3H]5-HT uptake was pharmacologically similar in both preparations. However, citalopram possessed approximately 10-fold weaker affinity to prevent [3H]5-HT uptake in the guinea-pig preparation when compared to the rat and all of the tricyclic antidepressants assessed in the present studies (amitriptyline, nortriptyline, desipramine and imipramine) displayed higher affinity in the guinea-pig preparation when compared to the rat. It is concluded that the high affinity 5-HT uptake systems in the rat and guinea-pig cortex are similar but may not be identical.
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PMID:Pharmacological comparison of the rat and guinea-pig cortical high affinity 5-hydroxytryptamine uptake system. 157 79

Interneurons from the CA1 lacunosum-moleculare (L-M) region were isolated by trypsin-hyaluronidase treatment and mechanical trituration of the L-M. Interneurons isolated in this manner were multipolar with several dendritic processes and could be distinguished from CA1 pyramidal neurons. The properties of a low-threshold transient (LTT) Ca2+ current were investigated using whole-cell voltage-clamp techniques. The activation threshold of the LTT Ca2+ current was -60 mV, and the peak current, 100 +/- 9 pA (mean +/- SEM; n = 15), was observed at -30 mV. Ca2+ was the predominant charge carrier because the current was not affected by tetrodotoxin and was abolished in Ca(2+)-free external solution. Steady state inactivation was observed when the holding potential was positive to -100 mV, and the current was half-inactivated at -84 mV. Complete inactivation occurred at a holding potential of -60 mV. The time-to-peak of the current was highly voltage dependent and ranged from 10 msec at -60 mV to 4 msec at 0 mV. The time constant of inactivation was also voltage dependent and ranged from 27 msec at -60 mV to 12 msec at greater than -30 mV. Recovery from inactivation to 90% of maximum current occurred within 200 msec. L-M interneurons receive synaptic inputs from the septum that release ACh or GABA and from the raphe nuclei that release 5-HT. Carbachol, a nonhydrolyzable cholinergic agonist, and 5-HT quickly and reversibly increased the amplitude of the LTT Ca2+ current. Carbachol's actions were blocked by atropine, indicating that this effect was mediated by muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low-threshold transient calcium current in rat hippocampal lacunosum-moleculare interneurons: kinetics and modulation by neurotransmitters. 167 22

The effect of fluoxetine hydrochloride, a 5-HT uptake inhibitor (60 mg/day PO), in preventing weight gain associated with nicotine reduction was investigated in participants in a double-blind, placebo-controlled smoking-cessation trial. A lunch of cheese pizza and chocolate bars was offered, and caloric intake was monitored. The analysis focused on subjects (placebo: n = 11; fluoxetine: n = 10) who succeeded in reaching cotinine levels of less than 50% of their starting cotinine levels (signifying a stringent reduction in nicotine intake) and who participated in pre- and post-nicotine reduction lunch sessions 70 days apart. Subjects on placebo gained significantly more weight (mean +/- SEM = +3.3 +/- 0.7 kg) than subjects on fluoxetine (-0.6 +/- 1.2 kg). In fluoxetine-treated subjects, weight gain/loss was strongly correlated with initial body mass index, with higher BMI being associated with greater decreases in weight. A trend towards decreased caloric intake in the fluoxetine group was observed; the change in total calories at lunch was significantly correlated with weight change, an association accounted for principally by change in pizza intake. We conclude that fluoxetine treatment effectively prevents the weight gain that accompanies nicotine reduction and that this phenomenon is mediated, at least in part, by diminished caloric intake.
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PMID:Effects of fluoxetine on weight gain and food intake in smokers who reduce nicotine intake. 180 94

1. Reserpine (5 mg/kg intraperitoneally) produced gastric mucosal vasoconstriction and injury in all rats within 6 h (injury score 38.8 +/- 2.1 mm2, mean +/- SEM). Coeliac ganglionectomy or the beta-adrenoceptor-blocking drug propranolol (5-15 mg/kg) did not influence these effects of reserpine, but vagotomy protected the rats against them. The alpha-adrenoceptor-blocking drugs phenoxybenzamine and phentolamine at 5 mg/kg were protective against injury. However, a 10 mg/kg dose of either blocker was more effective (2.2 +/- 0.5 mm2 and 3 +/- 0.8 mm2, respectively, versus 38.8 +/- 2.1 mm2, mean +/- SEM, P less than 0.01) and a dose of 15 mg/kg afforded complete protection. 2. Methysergide, a 5-hydroxytryptamine receptor antagonist, produced a dose-dependent increase in the reserpine-induced injury; a significant (P less than 0.05) increase was noted with 15 and 20 mg/kg (47.5 +/- 2.9 mm2 and 49.4 +/- 2.2 mm2, respectively, versus 38.8 +/- 2.1 mm2, mean +/- SEM). 3. The results suggest that, in the rat, reserpine causes vagal alpha-adrenoceptor stimulation producing gastric mucosal vasoconstriction and injury. 5-Hydroxytryptamine is not implicated in the mechanism of this injury and affords protection against it.
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PMID:Mechanism of reserpine-induced acute gastric mucosal injury in the rat: role of endogenous 5-hydroxytryptamine. 184 92

It is very important to find suitable reaction conditions to attain a high specific binding (specific/total binding) in the receptor binding study. Membrane homogenates of pig choroid plexus are known to have exclusively serotonin (5-hydroxytryptamine, 5-HT) receptor of the subtype 5-HT1c. In this study, we used the membrane preparation of pig choroid plexus tissue and the specific binding of [3H]5-HT was 72-84% to serotonin receptor subtype 5-HT1c, as defined by the inhibition of 1 uM 5-HT, when a radioligand concentration of 0.5 nM of [3H]5-HT was used in the assay. Analysis of the properties of specific [3H]5-HT binding in pig choroid plexus tissue membrane preparation revealed linear Scatchard plots. In Tris-HCl buffer without CaCl2, pargyline or ascorbic acid, high average of affinity dissociation constant (Kd) of 1.3 +/- 0.2 nM (SEM, n = 4) and also a high average of receptor density (Bmax) of 284 +/- 12 fmol/mg of protein were found. Pig choroid plexus proves to be a good material for 5-HT1c receptor binding study.
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PMID:Serotonin (5-HT1c) receptors in pig choroid plexus. 184 41

Two dopamine receptors are present on the renal vasculature: post-synaptic D1-receptors and neuronal D2-receptors. The existence of postsynaptic vascular D2-receptors is now under discussion. The aim of this study was to characterize in vitro the renal vascular response to bromocriptine, a D2 preferential agonist. Bromocriptine (10(-7) to 3.10(-5) M) induced a concentration dependent relaxation (EC50 = 1.4 +/- 0.1 x 10(-6) M, m +/- SEM, n = 5) on the isolated perfused rat kidney whose vascular tone had been previously increased by 25% with prostaglandin F2 alpha and adrenoceptors blocked (phenoxybenzamine 10(-5) M, sotalol 10(-5) M). Response to bromocriptine was comparable to that induced by dopamine on terms of EC50 and Emax (87 +/- 3% reversion of the increase in renal vascular resistance induced by prostaglandin F2 alpha). Nevertheless, unlike response to dopamine, bromocriptine-induced relaxation was not antagonized by the selective D1-receptor antagonist, SCH 23390 (3 x 10(-9) M) but was inhibited by selective D2-receptor antagonists, domperidone (10(-8) M) and DO 710 (3 x 10(-8) M). To account for renal vasodilatation, an interaction of bromocriptine with 5-HT receptors was excluded. Indeed, neither 8-OHDPAT, 5-methoxytryptamine nor 5-HT were able to induce any renal vasodilatation on the isolated perfused rat kidney and domperidone is devoid of antagonist activity on 5-HT receptors. The present results suggest that bromocriptine-induced vasodilatation on the rat renal vascular bed was linked to an interaction with vascular postsynaptic D2-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Do renal vascular D2 receptors exist?]. 195 69


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