Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human saphenous vein preincubated with [3H]noradrenaline was used to determine the pharmacological properties of the release-inhibiting presynaptic serotonin (5-HT) receptor on the sympathetic nerves. The overflow of tritium evoked by transmural electrical stimulation (2 Hz) was concentration-dependently inhibited by drugs known to stimulate 5-HT receptors in the following rank order: oxymetazoline greater than or equal to 5-HT greater than 5-carboxamidotryptamine = 5-methoxytryptamine = sumatriptan greater than tryptamine greater than N,N(CH3)2-5-HT = yohimbine = 8-hydroxy-2-(di-n-propylamino)-tetraline. The potencies of these agonists in inhibiting overflow were significantly correlated with their affinities for 5-HT1B and 5-HT1D binding sites, but not with those for 5-HT1A or 5-HT1C binding sites. 5-Aminotryptamine, methysergide, ipsapirone, cyanopindolol, SDZ 21009 and metergoline dit not produce a significant inhibition. Metitepine and methysergide antagonized the inhibitory effect of 5-HT, whereas spiroxatrine, propranolol, ketanserin and ICS 205-930 did not. These data exclude the idea that the inhibitory presynaptic 5-HT receptor on the sympathetic nerves belongs to the 5-HT2 and 5-HT3 receptor class; the pattern of agonist potencies suggests that the receptor is very similar to the 5-HT1D receptor subtype.
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PMID:Inhibition of noradrenaline release from the sympathetic nerves of the human saphenous vein via presynaptic 5-HT receptors similar to the 5-HT 1D subtype. 225 30

Increasing brain 5-hydroxytryptamine (5-HT) function in humans raises plasma concentrations of prolactin, growth hormone and ACTH. Measurement of these hormonal responses provides an index of the functional activity of brain 5-HT pathways. More recent strategies have included the use of directly-acting 5-HT receptor agonists to probe the function of specific receptor subtypes; at present these studies are limited by the questionable selectivity of the agonists employed. Using 5-HT neuroendocrine testing it can be shown that lithium specifically increases the prolactin release mediated by 5-HT pathways. Further studies are needed to determine if this effect is caused by an enhanced sensitivity of post-synaptic 5-HT1A receptors.
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PMID:5-HT neuroendocrine responses during psychotropic drug treatment: an investigation of the effects of lithium. 225 42

5-Hydroxytryptamine (5-HT) receptors of the 5-HT1A subtype are localized on serotoninergic cells and dendrites in the raphe nuclei of the brain stem and are believed to regulate synaptic 5-HT release through an inhibitory influence on serotoninergic impulse flow. The effects of 5-HT1A agonists on 5-HT release can, therefore, only be detected by measurement of 5-HT release from intact serotoninergic neurones. Here we review the evidence that the microdialysis technique, when applied to the anaesthetized rat, is able to detect extracellular 5-HT in the brain which derives from serotoninergic neurones and changes in accordance with serotoninergic neuronal activity. We have observed that a range of 5-HT1A agonists, including 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), inhibit 5-HT release in hippocampus, most probably by acting on somatodendritic 5-HT1A autoreceptors in the dorsal raphe nucleus. The inhibitory action of 8-OH-DPAT and several other selective 5-HT1A receptor active drugs on 5-HT release is sensitive to pindolol, further supporting the idea that the 5-HT receptor being measured is of the 5-HT1 subtype. Two drugs, BMY 7378 and NAN-190, which show 5-HT1A antagonist properties in certain models, reduce 5-HT release indicating that they have mixed agonist/antagonist actions at the 5-HT1A receptor. Our data indicate that measurement of 5-HT release in rat brain using the microdialysis technique may be a useful method to probe the pharmacology of the 5-HT1A autoreceptor in vivo.
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PMID:Application of brain microdialysis to study the pharmacology of the 5-HT1A autoreceptor. 225 48

Because a satisfactory animal model for migraine does not exist, attempts to determine a common mechanism of action for effective antimigraine agents may be of benefit in elucidating the pathogenesis of this neurologic syndrome. The present review demonstrates that the clinical data that has developed over the past 30 years may allow for the elucidation of the role of specific 5-HT receptor subtypes in the pathophysiology of migraine. A large number of both acute and prophylactic antimigraine agents share an ability to interact with 5-HT receptor subtypes in human brain. As summarized in Table 3, acute antimigraine drugs (e.g., ergots, sumatriptan) share high affinity for 5-HTID receptors and somewhat lower affinity for 5-HT1A receptors. These receptors are present in certain intracranial blood vessels. 5-HT1D receptors are also located on nerve terminals where they act to inhibit the release of 5-HT and other neurotransmitters. Theoretically, 5-HTID receptor agonists may acutely inhibit the release of vasoactive or pain-inducing substances in the perivascular space. Conceivably, drugs acting at this receptor would stop the progression of this perivascular process. In addition, a number of prophylactic antimigraine drugs display a relatively high affinity for both 5-HT2 and 5-HT1C receptors in human brain. Although these receptors are also found in certain blood vessels, they are present throughout the nervous system. The receptors appear to mediate neuronal depolarizations at the cellular level. Moreover, the 5-HT2 receptor appears to play a key role in the development of inflammation in certain smooth muscle systems. Theoretically, the ability of 5-HT2 antagonists to protect perivascular inflammation may account for their efficacy in the prophylactic treatment of migraine. These data offer a novel approach to the analysis of antimigraine agents. Drugs could be selected for use in clinical migraine studies based on their selectivity for a specific 5-HT receptor subtype. For example, an agent that displays both high affinity and selectivity for 5-HT1D receptors could be clinically evaluated. Its effectiveness, or lack thereof, would indicate the importance of this specific 5-HT receptor site in the pathogenesis of migraine. Future attempts to determine a common mechanism of action for effective antimigraine agents should facilitate the elucidation of the pathogenesis of this neurologic syndrome.
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PMID:Developments in 5-hydroxytryptamine receptor pharmacology in migraine. 225 14

Adult guinea pig hippocampal membranes contain two 5-hydroxytryptamine (5-HT) receptors positively coupled with an adenylate cyclase. One is a typical 5-HT1A receptor and the second is a nonclassical 5-HT receptor that we previously proposed to call 5-HT4. Here, we show that 4-amino-5-chlor-2-methoxy-benzamide derivatives are agonists of 5-HT4 receptors in guinea pig hippocampal membranes. Their effects on the adenylate cyclase of these membranes are not additive with those of 5-HT but are additive with those of RU 24969, a typical 5-HT1 agonist. The effects of benzamides, as well as those of 5-HT, on 5-HT4 receptors are not blocked by 5-HT1, 5-HT2, or 5-HT3 antagonists except ICS 205 903, which does so with a low affinity (1 microM). The potency of benzamides (cisapride greater than BRL 24924 greater than zacopride greater than BRL 20627 greater than metoclopramide) is similar to their effect of 5-HT4 receptors positively coupled with an adenylate cyclase of fetal mouse colliculi neurons.
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PMID:Pharmacological characterization of 5-hydroxytryptamine4(5-HT4) receptors positively coupled to adenylate cyclase in adult guinea pig hippocampal membranes: effect of substituted benzamide derivatives. 231 90

Measurements of endogenous levels of serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC), and biochemical and autoradiographic investigations on 5-HT and DA receptors were made in various brain regions in male rats at three different ages: 3 months, 10 months and 22 months. Age-dependent decreases in 5-HT levels associated with parallel increases in 5-HIAA/5-HT ratio were observed in the hypothalamus, striatum, hippocampus and cerebral cortex, suggesting an accelerated 5-HT turnover in aged rats. Similarly, DA levels were lower, and DOPAC/DA ratio was higher in the striatum of 22-month-old compared to 3-month-old or 10-month-old rats. Of the three different classes of 5-HT receptors which were examined, 5-HT1B sites exhibited the largest age-dependent decrease in density, followed by 5-HT2 sites, while 5-HT1A sites remained practically unchanged during aging. By comparison, the loss of striatal D2 receptors in 22-month-old rats compared to young adults was much greater than that of any 5-HT receptor subtype. Such differential age-dependent alterations of the various classes of 5-HT receptors and of dopaminergic versus serotoninergic synaptic markers might be responsible for at least some of the functional deficits in aged animals.
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PMID:Aging associated changes in serotoninergic and dopaminergic pre- and postsynaptic neurochemical markers in the rat brain. 238 3

The 5-hydroxytryptamine1A-receptor agonist 8-hydroxy-2-(n-dipropylamino) tetralin (8-OH-DPAT, 0.1 mg kg-1 i.v.) decreased the height of the extracellular 5-hydroxyindoleacetic acid (5-HIAA) oxidation peak recorded in the suprachiasmatic nucleus (SCN) of the anaesthetized rat by use of differential pulse voltammetry. The decrease in extracellular 5-HIAA produced by 8-OH-DPAT could be partially attenuated by prior administration of the non-selective 5-HT receptor antagonist methiothepin (1 mg kg-1 i.v.). The 5-HT2-receptor antagonist ritanserin (0.2 mg kg-1 i.v.) did not appear to block the effects of 8-OH-DPAT. The selective ligand for 5-HT1A recognition sites TVX Q 7821 (isapirone, 1 mg kg-1 i.v.) decreased the extracellular level of 5-HIAA in the SCN but to a lesser extent than 8-OH-DPAT. The response to 8-OH-DPAT was attenuated by prior administration of TVX Q 7821 to a level suggesting that TVX Q 7821 had blocked the effect of intravenous 8-OH-DPAT. Idazoxan (0.2 mg kg-1 i.v.) an alpha 2-adrenoceptor antagonist, completely blocked the effect of 8-OH-DPAT on the 5-HIAA oxidation peak recorded in the SCN, whilst having no effect on the 5-HIAA oxidation peak when given alone. At a dose of 0.5 mg kg-1 i.v. idazoxan induced a 120% increase in the height of the indole oxidation peak, suggesting that 5-HT release and metabolism in the rat SCN may be influenced by tonic adrenergic inputs. The data in this paper suggest that 5-HT1A- and alpha 2-receptors are involved in the effects of i.v. administered 8-OH-DPAT on 5-HT release and metabolism in the SCN in vivo.
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PMID:Involvement of 5-HT1A- and alpha 2-receptors in the decreased 5-hydroxytryptamine release and metabolism in rat suprachiasmatic nucleus after intravenous 8-hydroxy-2-(n-dipropylamino) tetralin. 243 Jun 56

The subdivision of serotonin (5-HT) receptors into three classes, designated 5-HT1, 5-HT2, and 5-HT3, has been based on radioligand binding studies and experiments in isolated tissues. As a result of radioligand binding studies, two types of 5-HT recognition sites have been postulated. One site specifically labeled by [3H]5-HT was termed 5-HT1, and the other one labeled by [3H]spiperone or [3H]ketanserin was designated 5-HT2. The pharmacological properties of the latter sites are obviously identical to those of the majority of the classical "D" receptors, whereas a smaller proportion of "D" receptors resemble the 5-HT1 type. Hence, according to the current definition, 5-HT1 and 5-HT2 receptors mediate effects previously ascribed to "D" receptors. Three subtypes of 5-HT1 binding sites, designated 5-HT1A, 5-HT1B, and 5-HT1C, can now be distinguished by improved binding assay with rather selective radioligands. The identity of a given 5-HT binding site with a 5-HT receptor was suggested by correlating the agonists' and antagonists' affinities for the binding site with their potencies to produce certain effects. This was further confirmed by the development of rather selective agonists and antagonists. A third class of 5-HT receptors, the "M" receptors, which are now designated 5-HT3 in order to distinguish them from muscarinic cholinoceptors, were identified in functional in vitro experiments. They are present on terminals of sympathetic and parasympathetic nerves and on afferent nerve fibers. All three receptor classes are involved in cardiovascular regulation.
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PMID:Classification of serotonin receptors. 244 65

The effects of eight serotonin (5-HT) receptor antagonists on the anorectic effect of d-fenfluramine (3.0 mg/kg, IP) were examined in a test of sweet mash consumption, using non-deprived male rats. d-Fenfluramine's effect was attenuated by the mixed 5-HT1/5-HT2 receptor antagonists, methiothepin and metergoline; by the 5-HT2 receptor antagonist ritanserin; and by (+/-)cyanopindolol, a mixed 5-HT1A/5-HT1B receptor antagonist. In contrast, d-fenfluramine's effect was not antagonised by the 5-HT2 receptor antagonists ketanserin and ICI 169 369; the 5-HT3 receptor antagonist ICS 205 930; or by xylamidine, a peripheral 5-HT receptor antagonist. In this feeding model, none of the 5-HT antagonists, when tested alone, had any effect to increase palatable food consumption. The pattern of results obtained strongly suggest that central 5-HT1 receptors play an important role in the mediation of d-fenfluramine-induced anorexia.
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PMID:Evidence that d-fenfluramine anorexia is mediated by 5-HT1 receptors. 249 30

The present study was undertaken to determine the involvement of serotonergic 5-HT1 and 5-HT2 receptor subtypes in stimulation of the secretion of prolactin. Several 5-HT agonists were administered, in a dose-response fashion, to conscious rats and the effect on the levels of prolactin in plasma was measured. The 5-HT1A + 5-HT1B agonist RU 24969 (5-methoxy-3[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole succinate) and the 5-HT1 + 5-HT2 agonist MK-212 (6-chloro-2-[1-piperazinyl]pirazine) increased levels of prolactin in plasma in a dose-dependent manner. In contrast, the selective 5-HT1A agonists 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino]tetralin) and ipsapirone (2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-1,2-benzisothiazol-3 -(2H) one-1,1-dioxidehydrochloride) did not increase levels of prolactin in plasma at any dose. The 5-HT-releasing drug, fenfluramine, also increased the concentration of prolactin in plasma. Pretreatment with the selective 5-HT2 antagonist, LY53857 (6-methyl-1-[1-methylethyl]ergoline-8-carboxylic acid, 2-hydroxy-1-methyl propyl ester (Z)-2-butenedioate [1:1]), did not significantly diminish an increase in levels of prolactin in plasma, induced by injection of fenfluramine. The antagonist LY53857 inhibited, but did not block the MK-212- and RU 24969-induced increase in the levels of prolactin in plasma. By deduction, these data suggest that 5-HT1B receptors, or as yet undefined 5-HT receptor subtypes may be involved in the stimulation of the secretion of prolactin by endogenously released 5-HT, and that 5-HT2 receptors may play a minor role in the serotonergic regulation of the secretion of prolactin.
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PMID:Effect of selective serotonin (5-HT) agonists and 5-HT2 antagonist on prolactin secretion. 252 77


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