Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The selective 5-HT1A receptor agonist 8-OH-DPAT increased serum corticosterone concentration in rats in a dose-dependent manner. The synthetic corticoid dexamethasone lowered the serum corticosterone level and abolished its rise induced by 8-OH-DPAT. The corticosterone response to 8-OH-DPAT was also antagonized by spiperone, (+/-)- and (-)-pindolol and (+/-)-propranolol, all of which have been shown to have a high affinity for 5-HT1A receptors, though in most cases no complete blockade was found. A partial antagonism of the response was also observed after flumazenil, a benzodiazepine antagonist. On the other hand, the 5-HT1B receptor antagonist 21009, the 5-HT2 receptor antagonists ketanserin and pirenperone, the 5-HT3 receptor antagonist ICS 205-930, the alpha 2-adrenoceptor antagonists yohimbine and idazoxan, the beta-adrenoceptor blocker with no affinity to 5-HT1 receptors, atenolol, the dopaminergic antagonist pimozide, the histamine receptor blocker chloropyramine and the opiate receptor antagonist naloxone did not affect the hormonal response to 8-OH-DPAT. The 8-OH-DPAT-induced corticosterone secretion was not affected either in rats pretreated with p-chlorophenylalanine (PCPA, an inhibitor of tryptophan hydroxylase) or p-chloroamphetamine (PCA, a drug-inducing lesion of serotonergic nerve terminals). It is concluded that 8-OH-DPAT-induced increase in serum corticosterone concentration results from its action at a site different than the adrenal cortex and is mediated by postsynaptic 5-HT1A receptors, whereas other subtypes (5-HT1B, 5-HT2, 5-HT3) of 5-HT receptors do not participate in this response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of corticosterone secretion by the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat. 253 May 90

The radiation inactivation technique has been used to estimate the molecular size of the 5-HT3 receptor binding site labelled by [3H]zacopride, in comparison with that of the 5-HT1A receptor binding site labelled by [3H]8-OH-DPAT, in rat cortical membranes. The calculated molecular weight of the 5-HT3 site: 35.4 +/- 2.2 kDa (mean +/- S.E.M., n = 4) was significantly less than that of the 5-HT1A site: 62.9 +/- 1.8 kDa (mean +/- S.E.M., n = 4) and of other 5-HT1 and 5-HT2 receptors of the G-protein coupled family. These data further support that the 5-HT3 receptor is not coupled to G-proteins in the rat brain.
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PMID:Determination of the molecular size of the 5-HT3 receptor binding site by radiation inactivation. 253 81

The activity of BRL 43694 (granisetron) was investigated using established models of 5-HT3 receptor activity. In guinea-pig isolated ileum, BRL 43694 antagonised the contractions evoked by relatively high concentrations of 5-HT (pA2 = 8.1 +/- 0.2). However, except in high concentrations, BRL 43694 did not affect the contractions of similar preparations of ileum, evoked by electrical field stimulation (cholinergically mediated), the nicotinic agonist dimethylphenyl piperazinium (DMPP) or by cholecystokinin octapeptide. Similarly, BRL 43694 did not affect electrically evoked, cholinergically mediated contractions of rat or human isolated stomach. In other models of 5-HT3 receptor activity (rabbit isolated heart, Bezold-Jarisch reflex in anaesthetised rats), potent antagonism by BRL 43694 was demonstrated. In radioligand binding studies on rat brain membranes, BRL 43694 had little or no affinity for 5-HT1A, 5-HT1B, 5-HT2 or for many other binding sites. BRL 43694 may therefore be a potent and selective 5-HT3 receptor antagonist.
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PMID:Selective and functional 5-hydroxytryptamine3 receptor antagonism by BRL 43694 (granisetron). 254 14

1. We have previously found that the putative 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) decreases hippocampal 5-hydroxytryptamine (5-HT) release in the anaesthetized rat, as measured by brain microdialysis. The present study attempted to characterize the receptor involved in this response using a range of monoamine receptor antagonists. 2. The classical 5-HT receptor antagonists, metergoline (5 mg kg-1 s.c.), methysergide (10 mg kg-1 s.c.) and methiothepin (10 mg kg-1 s.c.) each reduced dialysate levels of 5-HT which complicated their use as antagonists in these experiments. Nevertheless, pretreatment with metergoline but not methiothepin and methysergide partially reduced the 5-HT response to a maximally effective dose of 8-OH-DPAT (0.25 mg kg-1 s.c.). 3. The mixed 5-HT 1/beta-adrenoceptor antagonist pindolol (8 mg kg-1 s.c.) was without effect on spontaneous 5-HT output but attenuated the effect of both maximally (0.25 mg kg-1 s.c.) and submaximally (0.05 mg kg-1 s.c.) effective dose of 8-OH-DPAT. In comparison, propranolol (10 mg kg-1 s.c.) did not affect 5-HT output when injected alone and did not alter the response to 8-OH-DPAT (0.25 mg kg-1 s.c.). 4. The 5-HT2 receptor antagonist ritanserin (0.2 mg kg-1 s.c.) and the 5-HT3 receptor antagonist BRL 43694 (0.5 mg kg-1 s.c.) neither altered 5-HT output alone nor significantly changed the response to 8-OH-DPAT (0.25 mg kg-1 s.c.). 5. The 8-OH-DPAT (0.25 mg kg-' s.c.) response was not affected by pretreatment with either the dopamine D2-receptor antagonist sulpiride (10mgkg-1 s.c.) or the alpha/alpha 2-adrenoceptor antagonist phentolamine (10mg kg-1 s.c.). 6. We conclude from these data that the decrease of hippocampal 5-HT output induced by 8-OHDPAT does not involve 5-HT2, 5-HT3, adrenoceptors or dopamine D2-receptors and that activation of a 5-HT1 class of receptor seems probable. Full classification of the 8-OH-DPAT response awaits development of a suitably selective 5-HT1 receptor antagonist with low intrinsic activity at the somatodendritic 5-HT autoreceptor.
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PMID:Pharmacological characterization of 8-OH-DPAT-induced inhibition of rat hippocampal 5-HT release in vivo as measured by microdialysis. 257 66

DOI (1-100 micrograms/kg i.v.) induced an increase in mean blood pressure in the anaesthetized rat. Similarly, in the pithed rat, DOI (1-100 micrograms/kg i.v.) induced a dose-dependent increase in mean blood pressure, as did 5-HT. However, in contrast to 5-HT, DOI did not change the heart rate in either intact or pithed rats. In the pithed rat, the dose-pressor response curves to both 5-HT and DOI were unaffected by MDL 72222 (5-HT3 receptor antagonist), spiroxatrine or (+/-)-pindolol (5-HT1A receptor antagonists), idazoxan (alpha 2-adrenoceptor blocking agent) and AR-C 239 (alpha 1-adrenoceptor blocking agent). Only the selective 5-HT2 receptor antagonist. LY 53857, significantly and dose dependently shifted to the right the dose-response curves to both 5-HT and DOI. These results indicated that DOI possesses 5-HT2 agonistic properties and that the pressor response induced by DOI in the pithed rat is mediated via 5-HT2 receptors.
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PMID:Characterization of DOI, a putative 5-HT2 receptor agonist in the rat. 258 42

The effects of 5-hydroxytryptamine (5-HT) on the release of gamma-aminobutyric acid (GABA) were examined in the longitudinal muscle-myenteric plexus (LM-MP) preparation of guinea-pig ileum. 5-HT increased the spontaneous release and inhibited the electrically-evoked release of [3H]-GABA. The 5-HT-evoked release was Ca2+-dependent and tetrodotoxin-sensitive, and was antagonized by (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205-930), but not by methysergide and ketanserin. The inhibitory effect of 5-HT was antagonized by methysergide, but not by ketanserin and ICS 205-930. 8-Hydroxy-2-(di-n-propylamino)tetralin mimicked the inhibitory effect of 5-HT. Thus, 5-HT may exert an excitatory effect on the enteric GABAergic neurone via the 5-HT3 receptor and an inhibitory effect via the 5-HT1A receptor.
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PMID:Dual effects of 5-hydroxytryptamine on the release of gamma-aminobutyric acid from myenteric neurones of the guinea-pig ileum. 281 20

Serotonergic (5-HT) neuronal pathways regulate the release of adrenocorticotropin hormone (ACTH) from the pituitary gland probably through the action of hypothalamic corticotropin-releasing hormone (CRH). 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist, dose dependently (0.016-3 mg/kg s.c.) increased rat plasma ACTH concentration. This response was blocked stereoselectively by (-)-pindolol, known to have 5-HT1 antagonist properties, but not by (+)-pindolol, beta 1-, beta 2- or alpha 1-adrenoceptor, dopamine, muscarinic, 5-HT2 or 5-HT3 receptor antagonists. Similar increases of plasma ACTH were induced by other 5-HT1A receptor ligands (buspirone, ipsapirone and gepirone). These results suggest that activation of the 5-HT1A receptor induces the secretion of ACTH from the rat pituitary gland.
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PMID:Activation of the 5-HT1A receptor subtype increases rat plasma ACTH concentration. 289 20

Intravenous administration of the putative 5-HT1-like receptor agonist RU 24969 (10-1000 micrograms/kg) in anaesthetized rats induced a decrease in heart rate and blood pressure. The bradycardia was reduced, but not suppressed, by tertatolol, bilateral vagotomy or the combination of both treatments. The alpha 1-adrenoceptor blocking agent, AR-C 239, decreased the bradycardia induced by high doses of RU 24969. After treatment with hexamethonium, RU 24969 induced an increase in arterial blood pressure. The hypotensive response induced by RU 24969 was not altered by atropine. The hypotensive and bradycardic effects of RU 24969 were antagonized by methysergide (5-HT1-like receptor antagonist) and in part by spiroxatrine (5-HT1A receptor antagonist). Ketanserin (5-HT2 receptor antagonist) potentiated the effects of low doses of RU 24969. The cardiovascular effects of RU 24969 were antagonized neither by MDL 72222 nor by ICS 205-930 (5-HT3 receptor antagonists). The present results suggest that the cardiovascular effects of RU 24969 seem to be due to the stimulation of 5-HT1-like receptors. The participation of both 5-HT1A and 5-HT1B receptors subtypes has been considered. The results suggest a centrally-mediated inhibition of sympathetic tone and increase in vagal tone in the cardiovascular effects of RU 24969.
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PMID:Cardiovascular properties of a 5-HT1-like receptor agonist, 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969) in normotensive anaesthetized rats. 290 24

3H-5-Hydroxytryptamine (5-HT) binding sites were analyzed in bovine brain membranes. The addition of either the 5-HT1A-selective drug 8-OH-DPAT (100 nM) or the 5-HT1C-selective drug mesulergine (100 nM) to the assay resulted in a 5-10% decrease in specific 3H-5-HT binding. Scatchard analysis revealed that the simultaneous addition of both drugs decreased the Bmax of 3H-5-HT binding by 10-15% without affecting the KD value (1.8 +/- 0.3 nM). Competition studies using a series of pharmacologic agents revealed that the sites labeled by 3H-5-HT in bovine caudate in the presence of 100 nM 8-OH-DPAT and 100 nM mesulergine appear to be homogeneous. 5-HT1A selective agents such as 8-OH-DPAT, ipsapirone, and buspirone display micromolar affinities for these sites. RU 24969 and (-)pindolol are approximately 2 orders of magnitude less potent at these sites than at 5-HT1B sites which have been identified in rat brain. Agents displaying nanomolar potencies for 5-HT1C sites such as mianserin and mesulergine are 2-3 orders of magnitude less potent at the 3H-5-HT binding sites in bovine caudate. In addition, both 5-HT2- and 5-HT3-selective agents are essentially inactive at these binding sites. These 3H-5-HT sites display nanomolar affinity for 5-carboxyamidotryptamine, 5-methoxytryptamine, metergoline, and 5-HT. Apparent Ki values of 10-100 nM are obtained for d-LSD, RU 24969, methiothepin, tryptamine, methysergide, and yohimbine, whereas I-LSD and corynanthine are significantly less potent. In addition, these 3H-5-HT labeled sites are regulated by guanine nucleotides and calcium. Regional studies indicate that this class of sites is most dense in the basal ganglia but exists in all regions of bovine brain. These data therefore demonstrate the presence of a homogeneous class of 5-HT1 binding sites in bovine caudate that is pharmacologically distinct from previously defined 5-HT1A, 5-HT1B, 5-HT1C, 5-HT2, and 5-HT3 receptor subtypes. We therefore suggest that this class of sites be designated the 5-HT1D subtype of binding sites labeled by 3H-5-HT.
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PMID:Characterization of a novel 3H-5-hydroxytryptamine binding site subtype in bovine brain membranes. 295 4

5-Hydroxytryptamine (5-HT) inhibited the K+-induced release of [3H]acetylcholine [( 3H]ACh) from slices of the hippocampus of the rat, dose-dependently. Minaprine (3-(2-morpholinoethylamino)-4-methyl-6-phenylpyridazine, Fig. 1) had no effect on the release of [3H]ACh. However, it inhibited the (formula; see text) Fig. 1. Chemical structure of minaprine dihydrochloride. attenuation of the release of [3H]ACh by 5-HT dose-dependently. The 5-HT2 receptor antagonists, mianserine, methysergide and spiperone, prevented the inhibitory effect of the 5-HT, as well as did minaprine. The attenuating effect of 5-HT was not mimicked by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and was not prevented by a 5-HT1A and 5-HT1B mixed receptor antagonist, propranolol, or by the 5-HT3 receptor antagonists, cocaine and metoclopramide. Minaprine inhibited the bindings of [3H]5-HT, [3H]8-OH-DPAT and [3H]ketanserin in the hippocampus. The inhibitory effect of minaprine on the binding of [3H]ketanserin was more marked than on the binding of [3H]5-HT and [3H]8-OH-DPAT, and was non-competitive. The Ki value of minaprine for the binding of [3H]ketanserin was 2.9 microM. The inhibitory effect of 5-HT on the release of [3H]ACh was observed in the presence of tetrodotoxin. By electrolytic lesioning of the medial septum, the K+-induced release of [3H]ACh from the slices of hippocampus was significantly reduced and the release was no longer inhibited by 5-HT. The lesioning significantly decreased the binding of [3H]ketanserin in the hippocampus, with hardly any reduction in the binding of [3H]5-HT and [3H]8-OH-DPAT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin-2 receptor-mediated regulation of release of acetylcholine by minaprine in cholinergic nerve terminal of hippocampus of rat. 341 43


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