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)

Previous studies have shown that activation of the 5-HT1A receptor subtype enhances rat plasma ACTH concentration. Such receptors have been suggested to be located on CRH neuronal cell bodies in the paraventricular nuclei of the hypothalamus (PVN). In this report, microinjection of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a selective 5-HT1A agonist, into the PVN increased rat plasma ACTH concentration in a dose-related manner. Similar responses were observed when two other 5-HT1A agonists, busipirone and gepirone, were used. (+/-)-Pindolol, known to have 5-HT1A antagonist properties, blocked the effect induced by an optimal dose of 8-OH-DPAT after injection into the PVN. This same dose of 8-OH-DPAT also induced a decrease of hypothalamic CRH concentration, which was completely antagonized as well by pretreatment injection of (+/-)-pindolol into the PVN. A significant inverse correlation was found between hypothalamic CRH and plasma ACTH levels. These results confirm that elevation of the plasma ACTH concentration induced by 5-HT1A receptor subtype activation is mediated by the release of CRH from the paraventricular nuclei of the hypothalamus in rats, but do not exclude other mechanisms.
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PMID:Activation of 5-HT1A receptor subtype in the paraventricular nuclei of the hypothalamus induces CRH and ACTH release in the rat. 136 87

To study possible interactions between dopamine (DA) and serotonin (5-HT) neurochemical systems in the D-1 supersensitized induction of oral activity in neonatal 6-hydroxydopamine (6-OHDA) lesioned rats, the effects of a series of 5-HT agonists and antagonists were determined. At 3 days after birth rats were treated with desipramine HCl (20 mg/kg i.p., base form, 1 hr) and 6-OHDA HBr (100 micrograms, salt form, in each lateral ventricle). Rats were observed individually as adults, once a minute every 10 min over a 1-hr period after challenge with a DA or 5-HT receptor agonist. The respective 5-HT1A and 5-HT1B agonists, (+/-)-8-hydroxydipropylaminotetralin (0.50 mg/kg s.c.) and CGS 12066B maleate (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1, 2-alquinoxaline], 1:2 maleate salt; 3.0 mg/kg i.p.), did not increase oral activity. The mixed 5-HT1C and 5-HT2 receptor agonist, m-chlorophenylpiperazine (m-CPP), produced a slight increase in oral activity in control rats and a marked increase in oral activity in 6-OHDA-lesioned rats. In the 6-OHDA group the peak effect of 76.5 +/- 4.1 oral movements occurred with an m-CPP 2-HCl dose of 4.0 mg/kg. Pindolol (1.0 mg/kg i.p.), ketanserin tartrate (5 mg/kg i.p.) and MDL-72222 (3-tropanyl-3,5-dichlorobenzoate; 10 mg/kg s.c.), antagonists with high affinity for 5-HT1A,1B, 5-HT2 and 5-HT3 receptors, respectively, did not attenuate m-CPP actions. However, mianserin HCl (1.0 mg/kg s.c.), an antagonist with high affinity for 5-HT1C and 5-HT2 receptors, attenuated the oral response to m-CPP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Supersensitization of the oral response to SKF 38393 in neonatal 6-OHDA-lesioned rats is mediated through a serotonin system. 160 67

This study investigated the effects of (-)-pindolol, a putative 5-HT1A receptor antagonist, upon the central hypotensive action of the antihypertensive drug urapidil and of the purported 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in cats. Chloralose/urethane-anesthetized cats were thoracotomized and artificially ventilated. Blood pressure was monitored in the iliac artery, and the drugs were injected into the vertebral artery. Urapidil (1-300 nmol/kg) or 8-OH-DPAT (0.01-1 nmol/kg) dose-dependently reduced blood pressure. (-)-Pindolol (30 and 100 nmol/kg) shifted the dose-response curves of both drugs significantly and in a similar manner to the right. Doses of urapidil of 30 nmol/kg or higher also reduced the elevation of blood pressure following the intravenous injection of the alpha 1-adrenoceptor agonist cirazoline whereas 8-OH-DPAT was ineffective. Yet, the hypotensive response to the directly acting vasodilator nitroglycerin remained unchanged after urapidil. The results support the hypothesis that the centrally mediated component of the antihypertensive action of urapidil is due to stimulation of 5-HT1A receptors in the brainstem. Peripheral alpha 1-adrenoceptor blockade comes into play with higher doses of the drug administered via the vertebral artery.
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PMID:Involvement of 5-HT1A receptors in blood pressure reduction by 8-OH-DPAT and urapidil in cats. 170 92

Several recent studies have shown that the 5-HT1A agonist indorenate possesses antianxiety properties. In the present study we report on other behavioural actions of this drug. Indorenate (31.6 mg/kg) induced flat body posture, forepaw treading and hind limb abduction, behavioural characteristics of the serotonin syndrome. After indorenate injection these same behaviours were observed in animals pretreated with p-chlorophenylalanine (400 mg/kg X 3 days), suggesting that the action of this compound is not mediated via serotonin release. The beta-5-HT1 blockers, (-) pindolol (2 mg/kg) or (-) alprenolol (5 mg/kg), did not prevent the actions of indorenate on the serotonin syndrome. Indorenate (10 mg/kg) stimulated the masculine sexual behaviour by reducing the number of intromissions preceding ejaculation. Higher doses (17.8 mg/kg) cause a complete inhibition of sexual behaviour. (-) Pindolol (2 mg/kg) or (-) alprenolol (5 mg/kg) did not antagonize the facilitatory actions of indorenate on male sexual behaviour. A high dose of indorenate (31.6 mg/kg) resulted in an impairment of the motor coordination as tested in a treadmill apparatus. These data reveal that indorenate possesses, in addition to its antianxiety effects, other behavioural characteristics that, however, appear at higher dose levels.
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PMID:Behavioural actions of the serotonergic anxiolytic indorenate. 197 77

The effects of pindolol on the prolactin (PRL) and growth hormone (GH) responses to intravenous tryptophan (LTP) were studied in eight healthy male volunteers. Pindolol pretreatment (40 mg over 48 h) markedly attenuated the GH response to LTP and modestly, but significantly, reduced the LTP-induced increase in plasma PRL. The disposition of LTP following infusion was not altered by pindolol. While the data are consistent with 5-HT1A receptor mediation of PRL and GH responses to LTP, the intrinsic sympathomimetic actions of pindolol might also be involved in the attenuation of the endocrine responses to LTP.
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PMID:Pindolol decreases prolactin and growth hormone responses to intravenous L-tryptophan. 200 40

The aim of this study was to investigate the cardiovascular effects of the 5-HT1A receptor agonists, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), flesinoxan and 5-carboxamidotryptamine (5-CT) following injection into the dorsal raphe nucleus of conscious rats. 8-OH-DPAT (0.5-2.5 micrograms), hypotension, bradycardia and flat body posture. In contrast, injection of 8-OH-DPAT (0.5 microgram) into the median raphe nucleus caused no cardiovascular changes or flat body posture. (-)Pindolol (0.5 microgram dorsal raphe nucleus) had little effect on cardiovascular parameters, but significantly attenuated the cardiovascular effects of 8-OH-DPAT (0.5 microgram dorsal raphe nucleus). N-Methylatropine (1 mg/kg i.v.) antagonised the cardiovascular effects of 8-OH-DPAT (0.5 microgram dorsal raphe nucleus), suggesting these were vagally mediated. Both pretreatments also appeared to reduce 8-OH-DPAT-induced flat body posture. The results suggest that 8-OH-DPAT activates 5-HT1A receptors in the dorsal raphe nucleus to cause hypotension and bradycardia.
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PMID:Cardiovascular effects of 5-HT1A receptor agonists injected into the dorsal raphe nucleus of conscious rats. 214 24

Selective activation of the 5-HT1A receptor induces lower lip retraction (LLR) in rats. 8-Hydroxy-dipropylamino tetralin (8-OH-DPAT)-induced LLR could not be antagonised by the 5-HT antagonists methysergide, metergoline or mesulergine. In fact, some 5-HT antagonists induced LLR. However, 8-OH-DPAT-induced LLR could be antagonised by pindolol, spiperone, spiroxatrine and NAN-190, but not by the beta 1-adrenoceptor antagonist metoprolol, the beta 2-adrenoceptor antagonist butoxamine or the dopamine antagonist haloperidol. This antagonism was competitive as the dose-response curve of 8-OH-DPAT was shifted to the right. Pindolol, spiperone, spiroxatrine and NAN-190 all have a high affinity for the 5-HT1A receptor. This indicates that blockade of 8-OH-DPAT-induced LLR is only possible by selective blockade of 5-HT1A receptors. A possible mechanism of action is discussed. The increased defecation induced by 8-OH-DPAT could be antagonised by pindolol and NAN-190. The effect of spiroxatrine and haloperidol on the 8-OH-DPAT-induced increase in defecation was bimodal: an increase after a low and a decrease after a high dose of 8-OH-DPAT. Metoprolol and butoxamine had no effect on the 8-OH-DPAT-induced increase in defecation, thereby excluding an influence of beta-adrenoceptors.
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PMID:Antagonism of 8-OH-DPAT-induced behaviour in rats. 214 26

The serum corticosterone concentration in rats was increased by injection of quipazine, a relatively nonselective serotonin (5-hydroxytryptamine; 5-HT) agonist, or 8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT), a serotonin agonist selective for the 5-HT1A subtype of receptor. The quipazine-induced increase in serum corticosterone was antagonized by 17 different serotonin antagonists; of these, MDL 11939, pirenperone, setoperone, mianserin, LY 281067, ketanserin, ritanserin and clozapine have relatively selective affinity for the 5-HT2 subtype of receptor. The 8-OH-DPAT-induced increase in serum corticosterone was not antagonized by metergoline, the most potent antagonist of the quipazine effect, but was antagonized by pindolol or penbutolol, 5-HT1A receptor antagonists. Pindolol did not block the effect of quipazine. The results support earlier evidence that serum corticosterone concentration in rats can be increased by activation of either 5-HT1A or 5-HT2 receptors. Indirect-acting serotonin agonists - fluoxetine, L-5-hydroxytryptophan and p-chloroamphetamine - also increased serum corticosterone concentrations. The increases elicited by those agents, which earlier had been reported not to be blocked by metergoline pretreatment, also were not blocked by pretreatment with pindolol or with the combination of metergoline and pindolol. Thus, an involvement of a specific serotonin receptor subtype in the actions of these indirect agonists has not been established.
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PMID:Serotonin receptor subtypes involved in the elevation of serum corticosterone concentration in rats by direct- and indirect-acting serotonin agonists. 214 12

5-Hydroxytryptamine (serotonin, 5-HT) stimulates basal adenylyl cyclase activity in membranes from guinea pig or rat hippocampi, but 5-HT inhibits forskolin-stimulated adenylyl cyclase activity in these same membranes. The opposing effects of 5-HT on adenylyl cyclase activity indicate that distinct 5-HT receptors, positively and negatively coupled to adenylyl cyclase, are present in these membranes. Stimulation of adenylyl cyclase activity is mediated by two distinct 5-HT receptors. The receptor with lower affinity for 5-HT, designated as RL, is apparently homologous with a 5-HT receptor present in rat collicular membranes, but it is not homologous with the stimulatory receptor characterized in neuroblastoma hybrid cell (NCB-20) membranes. The receptor with higher affinity for 5-HT is homologous with the 5-HT1A binding site. The magnitude of stimulation by 5-HT1A receptors is variable with respect to stimulation by RL and is sometimes completely absent. Inhibition of forskolin-stimulated adenylyl cyclase activity, in membranes from either rat or guinea pig hippocampus or rat cortex, is a functional correlate of the 5-HT1A binding site. This inhibitory response was used to determine the pharmacological characteristics of drugs that reportedly have high affinity for 5-HT1A binding sites, such as 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (PAPP) and (-)pindolol. PAPP inhibited adenylyl cyclase activity in guinea pig hippocampal membranes with an EC50 value of 27 +/- 3 nM. (-)Pindolol was a partial agonist in inhibiting adenylyl cyclase activity in guinea pig and rat hippocampal membranes. Because of the low intrinsic activity of (-)pindolol, it was tested as an antagonist of the inhibition produced by 5-HT1A receptor agonists in rat hippocampal membranes. The Kb of (-)pindolol was 40 nM as measured by a Schild plot. (-)Propranolol was a simple competitive antagonist at the rat hippocampal receptor with a Kb value of 550 nM. In summary, guinea pig and rat hippocampal membranes possess two distinct populations of 5-HT receptors, a 5-HT receptor that mediates inhibition of adenylyl cyclase activity and is pharmacologically homologous with the 5-HT1A binding site, and a stimulatory receptor that appears to be homologous with the 5-HT receptor first characterized in infant rat collicular membranes.
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PMID:Stimulation and inhibition of adenylyl cyclase by distinct 5-hydroxytryptamine receptors. 222 10

Injections of 8-OH-DPAT (0.1-6 micrograms/kg) into the vertebral artery or into the cisterna magna (5 micrograms/kg) produced a dose-dependent decrease in blood pressure, heart rate and renal sympathetic nerve activity in intact anaesthetized dogs and baroreceptor-denervated dogs. 8-OH-DPAT reduced the renal sympathetic nerve activity without changing the blood pressure or heart rate in catecholamine-depleted animals. Methiothepin (0.2 mg/kg) injected into the vertebral artery reduced the blood pressure without changing the heart rate or renal sympathetic nerve activity in baroreceptor-denervated dogs. The pressor response to i.v. phenylephrine was largely attenuated. Subsequent administration of 8-OH-DPAT (3 micrograms/kg) into the vertebral artery failed to alter the sympathetic discharge. Methiothepin (0.2 mg/kg) injected into the vertebral artery reversed the sympatho-inhibitory effect of 8-OH-DPAT (3 micrograms/kg) injected by the same route without changing the blood pressure. (+/-)Pindolol (0.2 mg/kg) injected into the vertebral artery of baroreceptor-denervated dogs reduced the blood pressure and heart rate without changing renal sympathetic activity. Subsequent administration of 8-OH-DPAT (3 micrograms/kg) failed to alter the sympathetic discharge. Bilateral microinjection of 8-OH-DPAT (1 microgram) into the nucleus tractus solitarii or into the medullary raphe nuclei failed to alter the blood pressure, heart rate or renal sympathetic activity. In contrast, bilateral microinjections of 8-OH-DPAT into the ventrolateral pressor area (VLPA) (0.2 microgram) produced a marked decrease in blood pressure, heart rate and renal sympathetic nerve activity. These effects were prevented or reversed by microinjections of methiothepin (10 micrograms) at the same sites. These results indicate that the central sympatho-inhibitory effects of 8-OH-DPAT were due to the stimulation of 5-HT1A receptors located in the ventrolateral pressor area. 5-HT autoreceptors did not seem to be involved.
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PMID:Ventrolateral medullary pressor area: site of hypotensive and sympatho-inhibitory effects of (+/-)8-OH-DPAT in anaesthetized dogs. 252 13


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