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

Pigeons were trained to discriminate 0.3 mg/kg of the 5-HT1A receptor agonist 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) from saline. RU 24969 (5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole), at doses of 5.6-10 mg/kg, and eltoprazine (5.6 mg/kg), both mixed 5-HT1A/B agonists, substituted completely for 8-OH-DPAT, whereas 3.0-10 mg/kg of the 5-HT1B/C agonist TFMPP (1-(m-trifluromethylphenyl)piperazine) and 0.1-3.0 of the 5-HT3 antagonist MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) yielded only saline-appropriate responses. Substitution for 8-OH-DPAT by eltoprazine and RU 24969, which does not occur in rats, provides in vivo support for the suggestion that the absence of a 5-HT1B receptor in the pigeon allows more complete expression of 5-HT1A-mediated effects. BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)]8-azaspirol-[4.5]- decane-7,9-dione) attenuated the 8-OH-DPAT stimulus at doses from 1.0 to 10 mg/kg but, when administered alone, also resulted in approximately 40% 8-OH-DPAT-appropriate responding at the highest dose. NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalamido)butyl)-piperazine (0.3-3.0 mg/kg) produced a dose-dependent and complete antagonism of the 8-OH-DPAT-discriminative stimulus; administered alone NAN-190 resulted only in saline-key responding. NAN-190 also reversed the rate-decreasing effects of higher doses of 8-OH-DPAT. The beta-adrenoceptor antagonist (+/-)-pindolol (5.6-17 mg/kg) antagonized the discriminative stimulus effects of lower 8-OH-DPAT doses but was unable to block the effects of higher doses of 8-OH-DPAT. Prazosin (1.0-10 mg/kg), which like NAN-190, is an alpha 1-antagonist, neither substituted for nor blocked the discriminative stimulus effects of 8-OH-DPAT. These results suggest that NAN-190 is an effective 5-HT1A receptor antagonist in this procedure with pigeons, with no indication of agonist actions, whereas BMY 7378 and pindolol are best characterized as partial 5-HT1A receptor agonists.
 ...
PMID:Discriminative stimulus effects of 8-OH-DPAT in pigeons: antagonism studies with the putative 5-HT1A receptor antagonists BMY 7378 and NAN-190. 142 37

We recently described a 5-hydroxytryptamine 5-HT1-like receptor mediating contraction in guinea-pig isolated iliac artery. The present study was aimed at characterizing this receptor with respect to the currently recognized 5-HT1 receptor subtypes (5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D). The potencies of 13 drugs tested as agonists correlated with their affinities for 5-HT1D binding sites only. The concentration-response curve for 5-carboxamidotryptamine (5-CT, a 5-HT1-like receptor agonist) was unaffected by propranolol (10 microM), which is reported to have affinity for 5-HT1A, 5-HT1B and 5-HT1C recognition sites. Yohimbine (3 microM) and metergoline (1 microM) antagonized 5-CT with pKB values of 6.15 and 6.96, respectively. These values are close to those found in a functional correlate of 5-HT1D sites in the same species, namely the presynaptic 5-HT autoreceptor in guinea-pig brain cortex. The overall results support the view that the receptor studied is of the 5-HT1D subtype. The receptor shares close similarities with other vascular 5-HT1-like receptors mediating contraction, for example the receptor present in dog saphenous vein.
 ...
PMID:Further characterization of the 5-hydroxytryptamine 5-HT1-like receptor mediating contraction of guinea-pig iliac artery. 142 55

Administration of m-chlorophenylpiperazine [m-CPP, a serotonin (5-HT) agonist] to rats increases plasma concentrations of prolactin and corticosterone. Pretreatment with various doses of ritanserin (5-HT1C/5-HT2 antagonist), ICS 205-930 and MDL-72222 (5-HT3 antagonists), iodocyanopindolol or CG361A (beta adrenoceptor antagonists) and spiperone (5-HT1A/5-HT2 antagonist) did not attenuate m-CPP-induced increases in plasma concentrations of prolactin. In contrast, pretreatment with various doses of metergoline (5-HT1/5-HT2 antagonist), propranolol (beta adrenoceptor antagonist that also has binding affinity for 5-HT1A, 5-HT1B and 5-HT1C sites), mesulergine and mianserin (5-HT1C/5-HT2 antagonists) attenuated m-CPP-induced increases in plasma prolactin. On the other hand, m-CPP-induced increases in corticosterone concentrations were attenuated only by pretreatment with a low dose of mianserin and a high dose of spiperone. When administered without m-CPP, metergoline, mesulergine, ritanserin, ICS 205-930 and high doses of mianserin, spiperone and propranolol increased plasma corticosterone secretion. On the other hand, none of the antagonists used in the present study, except spiperone, had any significant effect on plasma prolactin secretion. These findings suggest that m-CPP-induced prolactin secretion is mediated by stimulation of 5-HT1C receptors while corticosterone secretion may be mediated either by an antagonistic effect at 5-HT3 receptor subtype or by nonserotonergic mechanisms. Alternatively, enhancement of corticosterone secretion by the 5-HT antagonists when administered alone may be responsible for their failure to block m-CPP-induced corticosterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of various serotonin receptor subtype-selective antagonists alone and on m-chlorophenylpiperazine-induced neuroendocrine changes in rats. 143 90

Serotonin (5-HT) effects on physostigmine (PHY)-induced yawning were studied in LY Sprague-Dawley rats by injecting Lu 10 171 (citalopram), a specific 5-HT uptake blocker, and two antagonists--methiothepine and ritanserin--which differ slightly in the selectivity of their actions on different 5-HT receptor subtypes. Infant and young rats show significant increases in PHY-induced yawning when preinjected with citalopram (5-10 mg/kg). Two-month-old animals show this effect only with 10 mg/kg. With adult animals (3-5 months old), the effect is the opposite: Yawning decreases. The facilitory effect in infant and young rats was counteracted by methiothepine but not by ritanserin, suggesting that it is mediated through 5-HT1A or 5-HT1B receptor subtypes. The inhibitory effect of citalopram in adult rats was unmodified by the two antagonists used, leaving open the possibility that it is mediated by 5-HT3 receptors.
 ...
PMID:Age-dependent changes in serotonergic modulation of yawning in the rat. 143 84

The aim of the present study was to resolve which hypothalamic nucleus is necessary for the serotonergic control of renin secretion. RU 24969 is considered a serotonin (5-HT1A/5-HT1B) agonist, while p-chloroamphetamine is a 5-HT releaser. Both drugs reliably elevate plasma levels of renin when injected peripherally. Previous studies suggest that serotonergic neurons, projecting to the hypothalamus, mediate the effect of p-chloroamphetamine on renin secretion. Discrete cell-selective lesions were made with ibotenic acid in three hypothalamic sites: the paraventricular, the dorsomedial or the ventromedial nuclei. Two weeks after surgery rats were injected with RU 24969 (5 mg/kg, i.p.) or p-chloroamphetamine (8 mg/kg, i.p.). The renin response to both RU 24969 and p-chloroamphetamine was significantly reduced in rats with histologically verified paraventricular lesions compared to vehicle treated controls. In contrast, the renin response to p-chloroamphetamine remained unchanged in rats with either dorsomedial or ventromedial hypothalamic lesions. Thus, these results are consistent with the hypothesis that 5-HT receptors located on cell bodies in the paraventricular nucleus mediate the renin response to a serotonin agonist and releaser. Furthermore, they confirm previous studies that suggest that 5-HT neurons regulate renin secretion through central receptors.
 ...
PMID:Neurons in the hypothalamic paraventricular nucleus mediate the serotonergic stimulation of renin secretion. 145 11

Brain 5-HT1A and 5-HT1B receptors are important targets for drug-induced modulation of 5-HT function in vivo. However, very few compounds are available that are effective antagonists at 5-HT1 receptors, thus hampering the progress of fundamental as well as clinical research in this area. The present study assessed the usefulness of the beta-adrenolytic agent (-)-penbutolol (and its (+)-counterpart) as a 5-HT1A receptor-blocking agent. The compound was found to counteract, in a stereospecific fashion, not only the behavioural and hypothermic but also the in vivo 5-HT synthesis/turnover-reducing effects of the specific 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). These findings indicate that (-)-penbutolol is an antagonist at both postsynaptic receptors and somatodendritic autoreceptors of the 5-HT1A subtype. Thus, (-)-penbutolol represents a useful addition to the array of pharmacological tools available for the study of central 5-HT1 receptor-mediated functions.
 ...
PMID:(-)-Penbutolol as a blocker of central 5-HT1A receptor-mediated responses. 146 87

To investigate a possible functional interaction between 5-HT1B and 5-HT1A or 5-HT2 receptors we studied the effects of 5-HT1A selective agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and gepirone, of a 5-HT1A/5-HT2 agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and of a putative 5-HT2 agonist (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (+/- DOI) on the 5-HT1B receptor-mediated hypothermia induced by m-trifluoromethylphenylpiperazine (TFMPP) (25 mg/kg) or m-chlorophenylpiperazine (m-CPP) (20 mg/kg) in mice. 8-OH-DPAT (1.25-5 mg/kg), gepirone (1.25-5 mg/kg), 5-MeODMT (2-8 mg/kg) and (+/-)DOI (0.5-2 mg/kg) reduced dose-dependently the TFMPP- or m-CPP-induced hypothermia. At the same time 8-OH-DPAT (2.5 and 5 mg/kg, but not 1.25 mg/kg) and gepirone (1.25-5 mg/kg) themselves decreased the body temperature in mice, while 5-MeODMT (2-8 mg/kg) and (+/-)DOI (0.5-2 mg/kg) did not affect it. The present results suggest that a functional interaction exists between 5-HT1B and 5-HT1A or 5-HT2 receptors.
 ...
PMID:Functional interaction between 5-HT1B and 5-HT1A or 5-HT2 receptors in mice. 147 May 63

Although numerous subtypes of serotonin [5-hydroxytryptamine (5-HT)] receptors have been identified in the newborn rat by radioligand binding studies, there have been few studies of the functional significance of these early receptors, most without the benefit of selective drugs. We performed acute dose-response and time course behavioral studies in 1-day-old rats with the putative selective agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5-HT1A), 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H-indole (RU 24969) (5-HT1B), and (+-)1-(2,5-dimethoxy-4-iodo-phenyl aminopropane)-2 (DOI) (5-HT2/1C). The agonists induced distinctive behavioral syndromes. The DOI syndrome mainly included rudiments of forepaw myoclonus and dystonic limb postures, but no shaking behavior (head shakes or wet-dog shakes) or spinal myoclonus, two key reference behaviors for its effects in adult rats. The most distinctive feature of the 8-OH-DPAT-induced syndrome was flat body posture. RU 24969 most significantly increased locomotor activity, inducing propulsive movements with episodic rests and sudden hindlimb jerks. These studies suggest that functional and differential activity of 5-HT1A, 5-HT1B, and 5-HT2/1C receptors occurs much earlier in the rat than previously appreciated. The absence of DOI-induced shaking behavior and spinal myoclonus, however, suggests incomplete maturation at the level of the receptor or effector pathways for these behaviors.
 ...
PMID:Serotonin receptor ontogeny: effects of agonists in 1-day-old rats. 147 12

A new potent, selective and p.o. active serotonergic [5-hydroxytryptamine (5-HT2)] receptor antagonist, SR 46349B [trans, 4-([3Z)3-(2-dimethylaminoethyl)oxyimino-3(2-flurophenyl++ +)propen-1-yl]phenol hemifumarate) has been characterized by a series of "in vitro" and "in vivo" methods. Based upon binding studies with 5-HT2 receptors in rat brain cortical membranes and blockade of 5-HT-induced contractions in isolated tissues (rabbit thoracic aorta, rat jugular vein, rat caudal artery, rat uterus and guinea pig trachea), SR 46349B showed high affinity for 5-HT2 receptors. Furthermore, SR 46349B displayed moderate affinity for the 5-HT1C receptor and had no affinity for the other 5-HT1 subclass (5-HT1A, 5-HT1B or 5-HT1D), dopamine (D1 or D2), "alpha" adrenergic (alpha-1 or alpha-2), sodium and calcium channel and histamine (H1) receptors. It did not interact with histamine (H1), alpha-1 adrenergic and 5-HT3 receptors in smooth muscle preparations. No inhibition of the uptake of norepinephrine, dopamine or 5-HT was seen. Based upon blockade of pressor responses to 5-HT in pithed rats and in vivo binding studies in mice, SR 46349B was found to be a potent and p.o. active 5-HT2 receptor antagonist with a relatively long duration of action. Behavioral experiments, including mescaline- and 5-hydroxytryptophan-induced head twitches and learned helplessness, as well as sleep-waking cycle and EEG spectral parameter studies, indicated that SR 46349B has a classical 5-HT2 psychopharmacological antagonist profile.
 ...
PMID:Biochemical and pharmacological properties of SR 46349B, a new potent and selective 5-hydroxytryptamine2 receptor antagonist. 150 Nov 21

Rats were treated by intraperitoneal injection for four weeks with either RU24969, a 5-HT1B and 5-HT1A agonist or imipramine, a 5-HT uptake inhibitor. Pre- and postsynaptic 5-HT receptors were measured to compare the effect of direct or indirect stimulation of the 5-HT autoreceptor (5-HT1B receptor). The 5-HT transport protein (5-HT uptake site), labelled with [3H]paroxetine, was unaffected after treatment with either one of the drugs. The density of 5-HT2 receptors, labelled with [3H]ketanserin, we found increased after treatment with RU24969 (Bmax = 161 fmol/mg protein) and decreased after treatment with imipramine (Bmax = 109 fmol/mg protein) as compared with control rats (Bmax = 134 fmol/mg protein). The 5-HT1B receptor was found decreased both by the imipramine treatment (Bmax = 106 fmol/mg protein) and the treatment with RU24969 (Bmax = 105 fmol/mg protein), compared with control rats (Bmax = 130 fmol/mg protein). The 5-HT1A receptor was found to be decreased after treatment with RU24969 (control: Bmax = 62 fmol/mg protein; RU24969-treated: 49 fmol/mg protein), but unchanged after treatment with imipramine (Bmax = 58 fmol/mg protein). These results correspond to what could be expected, if the 5-HT1B receptor is the 5-HT autoreceptor.
 ...
PMID:Serotonin receptors in the brain of rats treated chronically with imipramine or RU24969: support for the 5-HT1B receptor being a 5-HT autoreceptor. 150 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>