UNIPROT:P08908 - FACTA Search

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Query: UNIPROT:P08908 (5-HT1A)
5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The selective 5-HT1A agonists, 8-hydroxy-2-(di-n-dipropylamino)tetralin (8-OH-DPAT) and ipsapirone, and the 5-HT1A/5-HT1B agonist, 1-(m-trifluoromethylphenyl)piperazine, partially inhibited the carbachol-stimulated [3H]inositol phosphate formation in rat hippocampal slices. The effect of 8-OH-DPAT was antagonized by cyanopindolol. Selective 5-HT1B, 5-HT2 and 5-HT3 agonists were inactive. 8-OH-DPAT failed to affect the phosphoinositide turnover stimulated by KCl, quisqualate or noradrenaline in hippocampal slices and by carbachol in striatal or cortical slices. These results suggest that 5-HT1A receptors are negatively coupled to phosphoinositide phosphodiesterase in the hippocampus.
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PMID:5-HT1A receptor agonists inhibit carbachol-induced stimulation of phosphoinositide turnover in the rat hippocampus. 284 Feb 96

Norepinephrine (NE) has been shown to have a biphasic effect on evoked potentials in the CA1 region of the hippocampus of the rat in vitro, with a beta receptor mediating an increase and an alpha receptor eliciting a decrease in the amplitude of the population spike. The purpose of this study was to use selective alpha-adrenergic agonists and antagonists to determine the subtype of receptor mediating the depressant response of NE. The present investigations demonstrated that the selective alpha 1 agonist, phenylephrine (2-50 microM) elicited a dose-dependent depression of the amplitude of the population spike. Clonidine, a relatively selective alpha 2-agonist, also depressed the amplitude of the population spike, but only at concentrations (10 microM) that were inconsistent with a selective action upon alpha 2-receptors. Another alpha 2-agonist, alpha-methylnorepinephrine (100-400 nM) did not depress the amplitude of the population spike. The depressant effect of NE was antagonized by the nonselective alpha antagonist, phentolamine (0.5-50 microM) and the alpha 1-selective antagonist, prazosin (1 microM), but not by the alpha 2-selective antagonist, idazoxan (1-10 microM). Phentolamine and prazosin antagonized the response to phenylephrine but not to clonidine. The depressant effect of NE was not antagonized by the antagonist of serotonin and dopamine, spiperone (100 nM); conversely, the effect of 8-hydroxy-2-(di-n-propylamine) tetralin (50 microM), a 5-HT1A receptor-selective agonist, which also depresses the amplitude of the population spike, was not antagonized by phentolamine (5 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Noradrenergic depression of synaptic responses in hippocampus of rat: evidence for mediation by alpha 1-receptors. 284 79

Ipsapirone (TVX Q 7821, 2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-1,2-benzisothiazol-3- (2H)one-1, 1-dioxidehydrochloride), a new anxiolytic drug in respect of the evaluation of its effect on central 5-hydroxytryptamine (5-HT), noradrenaline and dopamine functions was studied. It was found that ipsapirone inhibits induced by 8-OH-DPAT and 5-methoxydimethyltryptamine (agonists of 5-HT1A receptors) behavioural effects (flat body posture and forepaw treading) in normal and reserpinized rats. Ipsapirone partly inhibited in rats but not in mice the 8-OH-DPAT-induced hypothermia. Ipsapirone, administered at high doses, decreased the body temperature in rats and mice, inhibited the 5-hydroxytryptophan-induced head twitches in mice and the tryptamine-induced convulsions and tremor in rats. In the hind limb flexor reflex preparation of the spinal rat only high doses of the drug inhibited stimulation induced by quipazine, m-chlorphenylpiperazine, 8-OH-DPAT and St 587 (an agonist of alpha 1-adrenoceptors). Ipsapirone did not block the fenfluramine- and m-chlorphenylpiperazine-induced hyperthermia in rats at an ambient temperature of 28 degrees C. The drug did not affect clonidine-induced sedation and inconsiderably attenuated clonidine-induced hypothermia in mice. It attenuated the d-amphetamine-induced locomotor hyperactivity in mice and rats but, given alone, decreased the locomotor activity. The obtained results indicate that ipsapirone exhibits 5-HT1A antagonistic effect, and only at high doses it can also produce an inhibitory effect on 5-HT2 and the alpha 1-adrenergic function.
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PMID:Central action of ipsapirone, a new anxiolytic drug, on serotoninergic, noradrenergic and dopaminergic functions. 288 95

Superfused strips of the human saphenous vein preincubated with 3H-noradrenaline were used to investigate the influences of serotonin (5-HT) receptor agonists and antagonists on the electrically evoked tritium overflow. 5-HT and the preferential 5-HT1A receptor agonist 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] concentration-dependently inhibited the evoked 3H overflow. The evoked 3H overflow was not affected by 0.1 or 1 mumol/l TVX Q 7821 (2-(4-[4-(2-pyrimidinyl)-1-piperazinyl]-butyl)-1,2-benzoisothiazol -3(2H)one-1,1-dioxide), which selectively binds to 5-HT1A sites; TVX Q 7821 10 mumol/l produced an increase in overflow. The inhibitory effect of 5-HT on the impulse-evoked 3H overflow was abolished by the nonselective 5-HT receptor antagonist metitepin, but was not attenuated by propranolol. Metitepin also abolished the inhibitory effect of 8-OH-DPAT on evoked 3H overflow, whereas the 5-HT2 receptor antagonist ketanserin was inactive in this respect. There was also no antagonism of the effect of 8-OH-DPAT by the alpha 2-adrenoceptor antagonist rauwolscine or the dopamine receptor antagonist flupenthixol. These results suggest that both 5-HT and 8-OH-DPAT inhibit noradrenaline release by activating inhibitory 5-HT receptors on the sympathetic nerves of the human saphenous vein. These receptors possess similarities to 5-HT1 recognition sites, but a further subclassification is not yet possible on the basis of the available data.
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PMID:Inhibitory presynaptic 5-hydroxytryptamine (5-HT) receptors on the sympathetic nerves of the human saphenous vein. 294 82

In experiments with both rats and mice the 5-HT agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT) were shown to produce reliable analgesic effects after acute administration (1 mg/kg SC) in the tail-flick, hot-plate and shock-titration tests of nociception. Prior treatment with the noradrenaline neurotoxin, N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4), systemically administered to both rats and mice abolished the analgesic effects of both the 5-HT agonist compounds in all the tests of nociception used. Intrathecal 6-hydroxydopamine (6-OHDA) treatment also abolished the analgesic effects of 8-OH-DPAT and 5-MeODMT; in the tail-flick test the analgesia induced by 8-OH-DPAT was reversed to an hyperalgesia. Biochemical analyses confirmed notable noradrenaline depletions in the spinal cord. It is concluded that an important interaction between presynaptic noradrenergic terminals and serotonergic receptor sites, possibly 5-HT1A, mediates spinal nociception processes.
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PMID:(+)-8-OH-DPAT and 5-MeODMT induced analgesia is antagonised by noradrenaline depletion. 295 56

The prejunctional and postjunctional 5-HT receptors of the canine saphenous vein were studied. The release of 3H-noradrenaline (3H-NA) from incubated saphenous vein strips was inhibited by 5-hydroxytryptamine (5-HT) in a concentration-dependent way (5-HT concentrations: 0.01, 0.1 and 1.0 mumol.l-1), but not by the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT; 1 and 10 mumol.l-1). The inhibitory effect of 5-HT was antagonized by metitepine and methysergide, but not by yohimbine, (-)-pindolol or ketanserin. In strips preincubated with 5-HT (1.2 mumol.l-1), the fractional release of 3H-NA was slightly reduced (paired experiments). 5-HT and 8-OH-DPAT caused concentration-dependent contractions of the saphenous smooth muscle. A parallel shift of the concentration-response curve for 8-OH-DPAT to the right was caused by metitepine and yohimbine, but not by ketanserin. The contractions caused by 5-HT were antagonized by metitepine and yohimbine (parallel displacement of the curves to the right), as well as by ketanserin and methysergide (with a depression of the upper part of the curve). Blockade of alpha-adrenoceptors (due to prazosin plus a low concentration of yohimbine) also resulted in a weak antagonistic effect. Ketanserin and metitepine displaced the noradrenaline concentration-response curve to the right. We conclude that the saphenous vein of the dog is endowed with prejunctional receptors of the 5-HT1 type which can not be classified as belonging either to the 1A or 1B subtype; and that at the postjunctional level 5-HT1 (possibly of the 1D subtype) and 5-HT2 receptors are present.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The actions of 5-hydroxytryptamine receptor agonists and antagonists at pre- and postjunctional level on the canine saphenous vein. 297 24

Phosphatidylinositol (Ptdlns) turnover has been studied in the primary culture of granule cells dissociated from the cerebellum of postnatal rat. Addition of serotonin (5-hydroxytryptamine, 5-HT) caused an increase (300-600% of control) of [3H]inositol monophosphate (IP1) accumulation in the presence of LiCl in cells prelabeled with [3H]myo-inositol. The EC50 and saturation concentrations of 5-HT were about 0.1 and 10 microM respectively. Some nonselective 5-HT receptor agonists, MK212, 5-methoxytryptamine, tryptamine and quipazine, were capable of stimulating IP1 accumulation; a selective 5-HT1A receptor agonist, 8-OH-DPAT, was ineffective. The 5-HT-induced response was potently blocked by several 5-HT2 receptor antagonists such as ketanserin, mianserin, spiroperidol and pyzotyline. The 5-HT-induced accumulation was dependent on the culturing time of granule cells with the maximal response seen in an 8-day culture. Norepinephrine (NE) also promoted an increased IP1 accumulation (300% of the control) with an EC50 of about 1 microM, while prazosin inhibited this NE-induced response with a Ki of about 0.2 nM. The responses induced by NE and 5-HT appeared to be additive. In addition, histamine in a dose-dependent manner enhanced the accumulation by about 100%; this histamine effect was blocked by triprolidine, an H1 receptor antagonist, but not by cimetidine, an H2 receptor antagonist. These results suggest that 5-HT, NE and histamine could be part of the neurotransmitter substances present in mossy fibers or other afferent nerve endings which innervate granule cells in vivo and that Ptdlns turnover regulated by their selective receptors on granule cells may play a role in modulating the excitatory function of these neurons.
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PMID:Serotonergic, adrenergic and histaminergic receptors coupled to phospholipase C in cultured cerebellar granule cells of rats. 303 21

1. The excitability of lumbar spinal motoneurones was studied in halothane-anaesthetized rats by recording with microelectrodes the amplitude of the population spike evoked antidromically by stimulation of the cut ventral roots. 2. Electrical stimulation of the nucleus raphe obscurus for 1 min at 20 Hz increased the population spike amplitude and, as shown by intracellular recording, depolarized motoneurones. This response could be mimicked by microinjection of DL-homocysteic acid into raphe obscurus but the response was not present in animals pretreated with the 5-hydroxytryptamine (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). 3. Microiontophoretically applied 5-HT had very similar effects on the extracellularly recorded population spike to those caused by stimulation of the raphe obscurus. These responses to 5-HT were larger in 5,7-DHT-pretreated animals. 4. The effects of 5-HT were potently mimicked by iontophoretically applied 5-carboxamidotryptamine but 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) was without effect. 5. Antagonists were applied by microiontophoresis and also by intravenous injection. Ketanserin, the selective 5-HT2 antagonist, did not antagonize the effects of 5-HT. Neither did the 5-HT3-receptor antagonist MDL 72222 or the selective 5-HT1 binding ligand cyanopindolol. 6. The non-selective 5-HT1/5-HT2-receptor antagonist methysergide was an effective antagonist of both the effects of 5-HT and the response to raphe obscurus stimulation. Methysergide did not reduce the excitatory effects of noradrenaline. 7. It is concluded that 5-HT application and stimulation of raphe obscurus increase the excitability of motoneurones by an action on a 5-HT1-like receptor which appears to be different from the 5-HT1A-and the 5-HT1B-binding sites characterized by others.
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PMID:Effects of 5-hydroxytryptamine agonists and antagonists on the responses of rat spinal motoneurones to raphe obscurus stimulation. 322 71

Peripheral 5-HT receptor-mediated responses were examined in pithed spontaneously hypertensive rats and normotensive wistar rats. Responses examined were: Pressor and depressor responses, tachycardia and inhibition of stimulation-evoked tachycardia. In pithed spontaneously hypertensive rats, 5-HT, but not the 5-HT1-selective agonist 5-carboxamidotryptamine, produced pressor responses, and these were potently antagonised by the 5-HT2-selective antagonists ketanserin and LY 53857. In pithed spontaneously hypertensive rats, the tachycardia to 5-HT was abolished by a combination of the 5-HT2 receptor antagonist LY 53857 and propranolol, suggesting that the tachycardia is mediated by 5-HT2 receptors and by release of noradrenaline. In pithed spontaneously hypertensive rats, 5-carboxamidotryptamine, 5-HT, and to a lesser extent the 5-HT1 receptor agonist RU 24969, but not the 5-HT1A receptor agonist 8-OH-DPAT, produced depressor responses which were antagonised by methysergide and metitepin, but which do not clearly fit with any of the 5-HT1 ligand binding sites. In pithed normotensive wistar rat, 5-carboxamidotryptamine was approximately 100 times more potent than 5-HT and 8-OH-DPAT at inhibiting the cardio-acceleration produced by single pulse electrical stimulation and this inhibition was antagonised by metitepin, so that the response is mediated by 5-HT1 receptors.
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PMID:Investigations of cardiovascular 5-hydroxytryptamine receptor subtypes in the rat. 336 8

The synthesis of a tritiated derivative of the 5-HT1A photoaffinity probe 8-methoxy-2-[N-n-propyl, N-3-(2-nitro-4-azidophenyl)aminopropyl]aminotetralin ([3H]8-methoxy-3'-NAP-amino-PAT) allowed the use of this probe for attempting the irreversible labeling of specific binding sites in rat brain membranes. Sodium dodecyl-sulfate-polyacrylamide gel electrophoresis of proteins solubilized from hippocampal microsomal membranes that had been incubated with 20 nM [3H]8-methoxy-3'-NAP-amino-PAT under UV light revealed a marked incorporation of 3H label into a 63-kilodalton protein termed PI. As expected of a possible correspondence between PI and 5-HT1A receptor binding sites, 3H labeling by the photoaffinity probe could be prevented by selective 5-HT1A ligands such as 8-hydroxy-2-(di-n-propylamino)tetralin, ipsapirone, buspirone, and gepirone and by N-ethylmaleimide, but not by the 5-HT2 antagonist ketanserin, noradrenaline- and dopamine-related drugs, monoamine oxidase inhibitors, and chlorimipramine. Furthermore, the regional and subcellular distributions of PI were identical to those of specific 5-HT1A binding sites. These results indicated that the binding subunit of the 5-HT1A receptor is a 63-kilodalton protein with a functionally important sulfhydryl group(s).
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PMID:Identification of the 5-HT1A receptor binding subunit in rat brain membranes using the photoaffinity probe [3H]8-methoxy-2-[N-n-propyl, N-3-(2-nitro-4-azidophenyl)aminopropyl]aminotetralin. 359 78

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