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)

Two subtypes of excitatory 5-hydroxytryptamine (5-HT) receptor, 5-HT1P and 5-HT3, are found on type 2-AH neurons of the guinea pig myenteric plexus. The 5-HT1P receptor mediates a slow and the 5-HT3 receptor a fast depolarization of these cells, however, the role of these receptors in the physiology of the gut is unknown. Renzapride (BRL 24924), a substituted benzamide, has previously been found to antagonize responses of myenteric neurons mediated by both 5-HT1P and 5-HT3 receptors. The effects on myenteric type 2-AH neurons of a structurally similar benzamide, zacopride, which unlike renzapride has S and R stereoisomers, were investigated to gain further insight into 5-HT receptor function. In contrast to renzapride, S-, but not R-zacopride, was found to mimic the 5-HT1P receptor-mediated slow response to 5-HT. Desensitization of 5-HT1P receptors with 5-HT inhibited slow depolarizing responses to S-zacopride, and desensitization with S-zacopride antagonized slow responses to 5-HT. Responses to S-zacopride were also inhibited by renzapride and the 5-HT1P receptor antagonist N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP). S-zacopride, like renzapride and 5-HT, presynaptically inhibited nicotinic fast excitatory postsynaptic potentials, an effect that can be mediated by 5-HT1P or 5-HT1A receptors. Both S and R stereoisomers of zacopride antagonized 5-HT3 receptor-mediated fast responses to 5-HT. Unlike 5-HTP-DP, neither zacopride or its stereoisomers nor renzapride inhibited the binding of 5-[3H]HT to 5-HT1P receptors. [3H]zacopride (5-10 nM) was found to bind to a site in the gut from which it could be displaced by a 1,000-fold excess of renzapride and S-zacopride (but not R-zacopride) greater than 5-HTP-DP much greater than the 5-HT3 receptor antagonist ICS 205-930. These observations suggest that, in addition to 5-HT3 receptors, there is a benzamide binding site on myenteric neurons that interacts with, but is distinct from, the 5-HT recognition site of 5-HT1P receptors. Benzamides may affect coupling of the 5-HT1P receptor to its effector.
 ...
PMID:Use of stereoisomers of zacopride to analyze actions of 5-hydroxytryptamine on enteric neurons. 198 11

5-Hydroxytryptamine (5-HT) receptors have been analyzed and related to potential roles played by 5-HT in the physiology of the enteric nervous system (ENS). Three subtypes of 5-HT receptor--5-HT1P, 5-HT3, and 5-HT1A--have been found on enteric neurons. Receptors have been identified by intracellularly recording the electrical activity of enteric neurons and by studying the binding of radioligands and polyclonal anti-idiotypic antibodies raised against antibodies to 5-HT. Radioligand binding has been assessed by rapid filtration and by radioautography. 5-HT1P receptors mediate slow depolarizations of myenteric neurons that are associated with a closure of K+ channels. These responses can be inhibited by N-acetyl-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP) and by the substituted benzamide, BRL 24924. 5-HT1P-like responses can be mimicked by 5- and 6-hydroxyindalpine, by another substituted benzamide, the S stereoisomer of zacopride, and by anti-idiotypic antibodies. 5-HT1P receptors can be labeled by 3H-5-HT and 3H-5-hydroxyindalpine with high affinity and are located on neurons of both enteric plexuses and on processes of intrinsic neurons in the gastrointestinal mucosa. A similar distribution of binding sites for anti-idiotypic antibodies is revealed by immunocytochemistry. Excitatory postsynaptic potentials (EPSPs) mediated by 5-HT are abolished by 5-HT1P antagonists. Blockade of 5-HT1P receptors is accompanied by acceleration of the rate of gastric emptying. Mucosal application of cholera toxin activates enteric neurons in both plexuses; this action is blocked by 5-HT1P or 5-HT3 antagonists and by anti-idiotypic antibodies. 5-HT3 receptors are responsible for fast depolarizations associated with increased membrane conductance. These responses are antagonized by ICS 205-930 and mimicked by 2-methyl-5-HT and anti-idiotypic antibodies. 5-HT1A receptors have been reported to mediate hyperpolarizing responses associated with a rise in membrane conductance. Hyperpolarizing responses are also elicited by the 5-HT1A agonists, 8-hydroxy-di-n-propylaminotetralin (8-OH-DPAT) and 5-carboxyamidotryptamine. It is proposed that 5-HT1P receptors and perhaps 5-HT3 receptors are involved in initiating the peristaltic reflex and in regulating gastric emptying. No physiologic role has yet been identified for 5-HT1A receptors in the ENS.
 ...
PMID:5-HT receptor subtypes outside the central nervous system. Roles in the physiology of the gut. 207 74

The mechanisms by which imipramine and dihydroergosine stimulate the 5-HT syndrome in rats and inhibit the head-twitch response in rats and mice were studied. Imipramine- and dihydroergosine-induced stimulation of the 5-HT syndrome was inhibited stereoselectively by propranolol, a high affinity ligand for 5-HT1 receptor sites, but not by ritanserin, a specific 5-HT2 receptor antagonist. (-)-Propranolol potentiated the inhibitory effect of imipramine, but not of dihydroergosine on the head-twitch response, while ritanserin was without effect. Neither imipramine nor dihydroergosine were able to stimulate the 5-HT syndrome in the animals pretreated with p-chlorophenylalanine. As expected, 8-OH-DPAT, a selective 5-HT1A receptor agonist, stimulated, and 5-HT1B agonists CGS 12066B and 1-(trifluoromethylphenyl)piperazine (TFMPP) failed to stimulate the 5-HT syndrome induced in rats by pargyline and 5-HTP administration. A higher dose of ritanserin inhibited the syndrome. While 8-OH-DPAT alone produced all behavioral components of the 5-HT syndrome, dihydroergosine or imipramine alone even at very high doses never produced tremor or a more intensive forepaw padding as seen when these drugs were given in combination with pargyline and 5-HTP. A single administration of (-)-propranolol also inhibited the head-twitch response. This effect lasted in mice longer than after ritanserin administration. In in vitro experiments dihydroergosine expressed approximately twenty-fold higher affinity for 3H-ketanserin binding sites than imipramine. The results suggest that imipramine and dihydroergosine possess two components--one stimulating the 5-HT syndrome in rats by a presynaptic, presumably 5-HT1A-mediated mechanism, and the other inhibiting 5-HT2 binding sites.
 ...
PMID:Do imipramine and dihydroergosine possess two components--one stimulating 5-HT1 and the other inhibiting 5-HT2 receptors? 211 65

The effects of different manipulations of brain serotonergic (5-HT) systems were investigated in Montgomery's conflict test, an animal anxiety model based on the animal's inborn urge to explore a new environment and its simultaneous fear of elevated, open spaces. The putative 5-HT1A receptor agonists buspirone, gepirone, ipsapirone and 8-OH-DPAT all produced anxiolytic-like effects in narrow low dose-ranges, while in higher doses the behavior returned towards that seen in controls and, after the highest doses of buspirone and gepirone, was suppressed below that of controls. The 5-HT precursor L-5-HTP produced a biphasic dose-response curve. In a single low dose an anxiolytic-like action was obtained, while in the highest dose a clear-cut anxiogenic-like action was observed. The 5-HT depleting agents parachlorophenylalanine (PCPA) and 5,7-dihydroxytryptamine (5,7-DHT) both produced anxiolytic-like effects. Thus, anxiolytic-like and anxiogenic-like effects after various manipulations of brain 5-HT neurotransmission can be obtained also in an animal anxiety model involving neither consummatory behavior nor punishment. The anxiolytic-like effects after all these treatments are suggested to be due to decreased brain 5-HT neurotransmission, while the anxiogenic-like effect obtained after the highest dose of L-5-HTP is suggested to derive from increased 5-HT neurotransmission. Furthermore, using a modified Vogel's conflict model it was investigated whether the anxiolytic-like effects obtained after PCPA and 5,7-DHT involve the GABAA/benzodiazepine (BDZ) chloride ionophore receptor complex. Both the BDZ receptor antagonist flumazenil and the GABAA receptor antagonist bicuculline counteracted the PCPA induced anticonflict effect in doses which did not affect the behavior per se.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serotonergic involvement in conflict behaviour. 213 17

The effects of carbamazepine (CBZ) on brain 5-hydroxytryptamine (5-HT) function were investigated in rodents pretreated with CBZ acutely or for 14 days. In behavioural experiments, mice pretreated with 14 days CBZ showed increased 5-HT2-mediated head twitch behaviour after injection of carbidopa (25 mg/kg) followed by 5-hydroxytryptophan (5-HTP, 100 mg/kg). However, no change in head twitches after 5-methoxy,N,N,-dimethyltryptamine (5MeODMT 5.0 mg/kg), a direct agonist, was observed. Chronic CBZ administration to rats did not alter either the behavioural syndrome induced by 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT, 1.0 mg/kg), an index of postsynaptic 5-HT1A responses, or hypothermia after 8-OH-DPAT (0.5 mg/kg) which is thought to reflect presynaptic 5-HT1A activity. Both hyperactivity and the behavioural syndrome seen after tranylcypromine (20 mg/kg) followed by L-tryptophan (100 mg/kg) were decreased by prior treatment with CBZ (14 days). Accumulation of 5-HTP after administration of the amino acid decarboxylase inhibitor NSD1015 (100 mg/kg) was decreased after acute CBZ (50 mg/kg) in hippocampus. However, after 14 days oral treatment no change in this measure of 5-HT synthesis was seen, in either hippocampus or frontal cortex. CBZ (50 microM) added to superfused brain slices did not affect potassium-stimulated [3H]-5-HT release. However, hippocampal slices from rats pretreated with CBZ (14 days) showed increased potassium-stimulated [3H]-5-HT release. CBZ (14 days) did not alter 5-HT2 binding in rat frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of carbamazepine on 5-hydroxytryptamine function in rodents. 213 52

5-Hydroxy-L-tryptophan (5-HTP), 25 mg kg-1 IP, in combination with the peripheral 5-HTP decarboxylase inhibitor benserazide, 25 mg kg-1 IP, and the selective inhibitor of neuronal 5-hydroxytryptamine (5-HT) re-uptake, zimeldine, 10 mg kg-1 IP, suppressed lordosis in ovariectomized female rats, treated with estradiol benzoate (EB) or with EB plus progesterone (P). The suppression of lordosis produced by 5-HTP was antagonized by the beta-receptor blocker (-)pindolol, which also is a selective 5-HT1 receptor antagonist, but not by the 5-HT2 receptor antagonists metitepine or pirenperone, nor by the beta-receptor blocker betaxolol. The EB- or EB plus P-activated lordosis was also suppressed by administration of the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Together, these observations indicate an important role of central 5-HT1A receptors in the mediation of lordosis behavior in the female rat.
 ...
PMID:Evidence for the involvement of central 5-HT1A receptors in the mediation of lordosis behavior in the female rat. 252 57

The study examined the effect of both oxaprotiline (OXA) enantiomers on the serotonin system in rats and mice. (+)-OXA and (-)-OXA partly inhibit the behavioral syndrome induced by 8-OH-DPAT and 5-methoxy-dimethyltryptamine (5-MeODMT) in normal and reserpinized rats. Imipramine and desipramine produced a similar but less potent effect. (+)-OXA and, to a lesser extent, (-)-OXA antagonized the m-chlorophenylpiperazine (m-CPP)-induced hypothermia in mice. Imipramine and desipramine produced no such effect. (+)-OXA attenuated the head-twitch response to L-5-HTP in mice, but (-)-OXA has no such action. Neither enantiomer inhibited the fenfluramine-induced hyperthermia in rats nor antagonized m-CPP-induced stimulation of hind limb flexor reflex of spinal rat. The obtained results indicate that both enantiomers may have a 5-HT1B-antagonistic action and a less potent 5-HT1A-antagonistic one; on the other hand, they shown no 5-HT2-antagonistic activity.
 ...
PMID:Pharmacological effects of oxaprotiline enantiomers on the central serotonin system. 253 22

The effects of the pyrimidinyl-piperazines buspirone, gepirone, ipsapirone and their common metabolite 1-(2-pyrimidinyl)-piperazine (PmP) as well as of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and L-5-hydroxytryptophan (L-5-HTP) were investigated in Montgomery's conflict test--an animal anxiety model based on the animal's inborn urge to explore a new environment and its simultaneous fear of elevated, open spaces. Subcutaneous buspirone (32-128 nmol/kg), gepirone (32-128 nmol/kg), ipsapirone (32-512 nmol/kg) and 8-OH-DPAT (50-200 nmol/kg), as well as intraperitoneal L-5-HTP (56 mumol/kg) produced anxiolytic-like effects. However, at higher doses the magnitude of these effects decreased and overall the dose-response curves displayed inverted U-shapes. The highest doses (2048 nmol/kg) of buspirone and of gepirone even decreased responding below control levels, possibly in part due to concomitant sedation/motor impairment. After L-5-HTP (448 mumol/kg) and PmP (512 nmol/kg) anxiogenic-like effects were observed. The results indicate that anxiolytic- and anxiogenic-like effects of drugs affecting central serotonergic neurotransmission can be obtained in a sensitive rat anxiety model which neither involves consummatory behavior nor punishment. The anxiolytic-like effects of these compounds may be due to their 5-HT1A agonistic properties. Moreover, the present data may provide support for a possible reciprocal association of presynaptic 5-HT1A receptors vs. postsynaptic 5-HT1A as well as 5-HT2 receptors with regard to anxiety.
 ...
PMID:Effects of 5-HT1A receptor agonists and L-5-HTP in Montgomery's conflict test. 256 24

Regional dopamine synthesis in the rat striatum was estimated by measuring DOPA accumulation following inhibition of cerebral aromatic L-amino acid decarboxylase by means of NSD-1015, 100 mg kg-1 intraperitoneally. In animals treated with reserpine, 5 mg kg-1 subcutaneously -18 h, there was a statistically significant increase in DOPA accumulation in the nucleus accumbens, the ventro-medial neostriatum, the dorso-lateral neostriatum and in the posterior limb of the neostriatum. This increase in DOPA accumulation was antagonized dose-dependently in the nucleus accumbens and ventro-medial neostriatum, but not in the other two regions, by treatment with the 5-HT1A receptor agonist 8-OH-DPAT, 0.15-2.4 mumol kg-1, whereas the partial dopamine D2 receptor agonist (-)3-PPP, 2.5-10.0 mumol kg-1, or the full dopamine D2 receptor agonist quinpirole, 0.05-0.8 mumol kg-1, antagonized the reserpine-induced increase in DOPA accumulation uniformly in all four regions of the striatum. The suppression of DOPA accumulation by 8-OH-DPAT in reserpine-treated animals, was completely antagonized by raclopride, 1 mumol kg-1, but not by (-)pindolol, 8 mumol kg-1. The accumulation of 5-HTP in all regions of the striatum as well as in the neocortex following decarboxylase inhibition and reserpine pretreatment, was also inhibited by 8-OH-DPAT, and this inhibition was unaffected by treatment with raclopride or (-)pindolol. It is concluded that 8-OH-DPAT, in addition to general effects on forebrain 5-hydroxytryptamine synthesis, selectively affects limbic forebrain dopamine synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Evidence for selective inhibition of limbic forebrain dopamine synthesis by 8-OH-DPAT in the rat. 257 Mar 61

Radioligand binding techniques have demonstrated the existence of 5-hydroxytryptamine (5-HT) binding subtypes: 5-HT2, 5-HT1A and 5-HT1B. These techniques have also indicated that certain drugs appear to show sub-type specificity: 8-hydroxy-2-(di-n-propylamino)tetralin(8-OH-DPAT), a 5-HT1A agonist; 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1-H indole (RU 24969), a 5-HT1B agonist; and ritanserin, a 5-HT2 antagonist. (-)-Propranolol is a 5-HT1 antagonist of uncertain sub-type specificity. An examination has been made in mice and rats of the behavioural and biochemical effects of these drugs to determine whether the binding sites have physiological functions and further characterise the behavioural models. Administration of carbidopa (25 mg kg-1) plus 5-hydroxytryptophan (100 mg kg-1) produced head-twitch behaviour in mice which was antagonized by ritanserin (ED50 = 65 micrograms kg-1) but not (-)-propranolol (20 mg kg-1). 8-OH-DPAT (1-10 mg kg-1 s.c.) and RU 24949 (5 mg kg-1 i.p.) did not produce head-twitch behaviour. 8-OH-DPAT decreased 5-HTP- but not 5-methoxy-N-N-dimethyltryptamine (5 mg kg-1)-induced head-twitch by a (-)-propranolol-insensitive mechanism. Locomotor activity produced in mice by RU 24969 (3 mg kg-1) was antagonized by (-)-propranolol (20 mg kg-1) but not the (+)-isomer. (-)-Propranolol did not antagonize the behaviour induced in rats. In mice, both 8-OH-DPAT and RU 24969 markedly inhibited whole brain 5-HT synthesis and this effect was not antagonized by (-)-propranolol. In rats, 8-OH-DPAT (3 mg kg-1 s.c.) produced all the behavioural changes seen after quipazine (25 mg kg-1). (-)-Propranolol inhibited the behaviour changes produced by both agonists, while ritanserin antagonized the behaviour produced by quipazine but not 8-OH-DPAT. It is concluded, therefore, that the 5-HT1A receptor exists between the 5-HT2 receptor and the behavioural effectors. 8-OH-DPAT (at 20 degrees C ambient temperature) rapidly decreased rat body temperature, an effect antagonized by (-)-propranolol but not ritanserin. Quipazine (at 27 degrees C ambient temperature, but not 20 degrees C) increased body temperature but the effect was not blocked by either antagonist. Ritanserin does not antagonize apomorphine-induced locomotion in either species. 9 We suggest that 5-HT-induced head-twitch behaviour in mice is a useful 5-HT2 receptor model and the temperature change following 8-OH-DPAT injection in rats may be a 5-HT,A model. While (-)- propranolol antagonizes 8-OH-DPAT effects in rat, it does not inhibit 8-OH-DPAT effects in mice, and instead antagonizes RU 24969-induced locomotion. Its status as a 5-HT, antagonist remains illdefined.
 ...
PMID:A behavioural and biochemical study in mice and rats of putative selective agonists and antagonists for 5-HT1 and 5-HT2 receptors. 258 May 82


<< Previous 1 2 3 4 5 6 7 Next >>