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)

The cholecystokinin (CCK) family of peptides and their receptors are widely distributed throughout the gastrointestinal and central nervous systems where they regulate secretion, motility, growth, anxiety, and satiety. The CCK receptors can be subdivided into at least two subtypes, CCKA and CCKB on the basis of pharmacological studies. We report here the purification of the CCKA receptor to homogeneity from rat pancreas by using ion-exchange and multiple affinity chromatographic separations. This allowed partial peptide sequencing after chemical/enzymatic cleavage and synthesis of degenerate oligonucleotide primers. These primers were used for initial cloning of the cDNA from rat pancreas by PCR. The predicted protein sequence of the cDNA clone contained the five partial peptide sequences obtained from the purified protein. Seven putative transmembrane domains suggest its membership in the guanine nucleotide-binding regulatory protein-coupled receptor superfamily. In vitro transcripts of the cDNA clone were functionally expressed in Xenopus oocytes and displayed the expected agonist and antagonist specificity.
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PMID:Purification, molecular cloning, and functional expression of the cholecystokinin receptor from rat pancreas. 131 82

To investigate the dependence of the satiating action of cholecystokinin (CCK) on serotonergic action at central 5-HT receptors, we examined the effect of systemic pretreatment with 8-OH-DPAT (a 5-HT1A agonist that decreases central 5-HT synthesis and release via an action at somatodendritic autoreceptors in the brainstem raphe) on the suppression of food intake induced by systemic administration of cholecystokinin octapeptide (CKK-8). 8-OH-DPAT significantly attenuated the satiating action of CKK-8. This result is consistent with the hypothesis that peripherally acting CCK recruits central serotonergic processes to elicit normal satiety.
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PMID:The 5-HT1A agonist 8-OH-DPAT attenuates the satiating action of cholecystokinin. 140 88

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

The effects of postmortem delay, time of storage, and freezing, thawing, and refreezing tissue samples were studied in postmortem rat brain using conditions that reflect the handling of postmortem human brain before neurochemical analysis. The levels of monoamines and metabolites in the striatum and cingulate and occipital cortex were measured using alumina extraction and HPLC methods. Binding of raclopride to dopamine D2, SCH-23390 to dopamine D1, ketanserin to serotonin 5-HT2, 8-hydroxy-2-(di-n-propylamino)tetralin to serotonin 5-HT1A, and cholecystokinin (CCK)-8 to CCK-B sites was measured in tissue homogenates from the striatum or fronto-parietal cortex. An 18-h postmortem delay before dissection and storage resulted in region-specific changes in monoamine and metabolite levels. Binding to striatal D1 and frontoparietal cortex CCK-B sites was reduced over the course of a 27-h postmortem delay. Binding to D2 and 5-HT sites was relatively stable. Storage of tissue for up to 8 months also resulted in region-specific changes in monoamine and metabolite levels. No changes in receptor binding were seen after long-term storage. Freezing, thawing, and refreezing tissue samples resulted in increased levels of striatal 3,4-dihydroxyphenylacetic acid and decreased binding to striatal D2 sites. These results demonstrate time-, temperature-, and storage-dependent regional differences in the stability of monoamines and their metabolites and in binding to various receptor sites. These differences in stability and binding should be accounted for to interpret accurately the effects of neurological disorders on neurotransmitter dynamics in postmortem human brain tissue.
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PMID:Postmortem stability of monoamines, their metabolites, and receptor binding in rat brain regions. 750 13

In order to investigate whether the inhibitory effect of systemically administered cholecystokinin (CCK) on food intake is dependent on an interaction with central 5-hydroxytryptamine (5-HT) processes, we examined the effects of pretreating rats that were deprived of food for various periods of time (22 h in Experiments 1 and 3, 3 h in Experiment 2, and 1 h in Experiment 4) with the 5-HT1A receptor agonists, 8-OH-DPAT or gepirone, on the suppression of feeding induced by intraperitoneal CCK. 8-OH-DPAT (100 micrograms/kg, Experiments 1 and 2) or gepirone (2 mg/kg, Experiments 3 and 4) administered subcutaneously 60 min prior to intraperitoneal injection of CCK (6 micrograms/kg) did not attenuate the suppressant effect of CCK on feeding in any of these experiments. The 5-HT1A agonists had no significant effects on food intake on their own. As it has been established that the doses of 8-OH-DPAT and gepirone used in this study decrease 5-HT function in the central nervous system, the present results indicate that it is unlikely that the inhibitory effect of systemically administered CCK on food intake is dependent on an interaction with intact central 5-HT systems.
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PMID:Pretreatment with the 5-HT1A receptor agonists 8-OH-DPAT or gepirone does not attenuate the inhibitory effect of systemically administered cholecystokinin (CCK) on food intake in rats. 776 May 84

Anti-anxiety drugs are widely used for patients with neurosis or psychosomatic diseases due to the stress of contemporary society. The high efficacy of benzodiazepine (BZD) or its analog, which contains diazepam, is well-known. While these compounds have strong anti-anxiety effects, it has recently been pointed out that they have some side effects when used as daytime tranquilizers and induce drug dependence. The cause of these side effects is thought to be that typical BZD is a full agonist of BZD receptors. For this reason, partial agonists, inverse agonists and antagonists of BZD receptors are being developed. Furthermore, some non-BZD anti-anxiety drugs are also being developed to avoid the side effects of BZD. One of these is a 5-HT1A agonist, which has a high affinity for 5-HT receptors, because it is reported that 5-HT is related to anxiety in the septum-hippocampus system. In addition, the anti-anxiety effect of 5-HT3 agonist is being investigated, while the anti-anxiety effect of cholecystokinin agonists is also attracting attention. Because these new anti-anxiety drugs are more potent and have fewer side effects than BZD, they may achieve widespread clinical use.
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PMID:[Recent progress in development of psychotropic drugs (1)--Anti-anxiety drugs]. 779 24

Serotonin (5-HT) produced concentration-dependent contractions of the isolated rat pylorus in vitro. Serotonergic contractions were antagonized by the calcium L-channel blocker, diltiazem, but not by tetrodotoxin or atropine. Three drugs that block 5-HT2 receptors, ketanserin, xylamidine, and methysergide, unsurmountably inhibited contractions to 5-HT. In contrast, antagonists of 5-HT3, 5-HT1A/1B, beta-adrenergic, or alpha 1-adrenergic receptors did not alter the response to 5-HT. Devazepide, an antagonist of cholecystokinin (CCK) type-A receptors, blocked contraction produced by CCK-8 but not by 5-HT. Conversely, the 5-HT2 antagonists did not affect CCK-stimulated contraction. These results suggest that 5-HT contracts the pylorus by a 5-HT2-like receptor on muscle and that this response occurs independently of CCKergic receptor mechanisms. Furthermore, the parallel between the overall pharmacological profile for serotonergic contraction of the pylorus and that observed previously for the anorectic action of peripheral 5-HT makes the pylorus a logical candidate for peripheral serotonergic control of feeding.
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PMID:Serotonin contracts the isolated rat pylorus via a 5-HT2-like receptor. 830 52

The present study determined the effect of pretreatment with "silent" selective 5-HT1A receptor antagonists on cholecystokinin (CCK)-mediated effects on rat behaviour in the elevated x-maze model of anxiety. In the absence of 5-HT1A receptor antagonists, non-sulphated cholecystokinin-octapeptide (CCK-8ns; 10 and 50 micrograms/kg, i.p.; 30 min prior to testing) produced an anxiogenic profile of behaviour on the x-maze, reducing the number of open arm entries and the number of exploratory head dips, while increasing the level of risk-assessment as measured by the number of stretched-attend postures. CCK-8ns did not, however, alter ambulatory activity. Two 5-HT1A receptor antagonists were employed in these experiments: (+)WAY100135 (the active enantiomer of N-tert-butyl-3-(4-(2-methoxyphenyl)piperzin-1-yl)- 2-phenylpropronamine) [sequence: see text] and WAY100635 (N-[2-[4(2-methoxyphenyl)-1-piperazinyl-1-piperazinyl]-N-2- pyridinyl)cyclohexanecarbonate [sequence: see text] trihydrochloride). When administered 10 min prior to CCK-8ns, (+) WAY100135 and 0.3 mg/kg s.c.) significantly attenuated profile of CCK-8ns. (+)WAY100135 was also demonstrated to significantly inhibit postsynaptic 5-HT1A receptor-mediated 8-OH-DPAT (8-hydroxy-2-(di-N-propylamino)tetralin)-induced 5-HT syndrome at the same dose used in the x-maze experiment. Neither (+)WAY100135 nor WAY100635 had any affects on ambulatory activity. These results support a CCK/5-HT1A receptor interaction in the modulation of aversion in rats exposed to the elevated x-maze.
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PMID:Attenuation of CCK-induced aversion in rats on the elevated x-maze by the selective 5-HT1A receptor antagonists (+) WAY100135 and WAY100635. 853 48

Several recent studies have suggested that feeding suppression is mediated jointly by enhanced neurotransmission of cholecystokinin (CCK) and serotonergic (5-HT) systems. In the present study the CCKA receptor antagonist devazepide (50-200 micrograms kg-1, s.c.) was found reliably to potentiate the feeding response elicited by dorsal or median raphe injection of the 5-HT1A agonist 8-OH-DPAT (0.2-0.8 nmol). This effect was evident following co-administration of both feeding threshold and subthreshold doses of either compound, suggesting that the simultaneous suppression of CCK and 5-HT function may interact as joint effectors of overeating.
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PMID:Effect of the CCKA antagonist devazepide on eating stimulated by raphe injection of 8-OH-DPAT. 874 64

Adult male Sprague-Dawley rats were administered the 5-HT subtype selective receptor agonists 8-OH-DPAT (0.5-2.0 mg/kg), buspirone (2-8 mg/kg) (5-HT1A), TFMPP (0.125-2.0 mg/kg) (5-HT1B), DOI (0.125-2.0 mg/kg) (5-HT2A) and m-CPBG (1.25-20.0 mg/kg) (5-HT3), subcutaneously. Oxytocin, cholecystokinin (CCK), somatostatin and gastrin plasma levels were determined by standard RIA techniques 30 and 120 min after injection of the respective 5-HT receptor agonist. It was found that the 5-HT1A and the 5-HT2A/C, but not the 5-HT2B or the 5-HT3 receptor agonists produced an increase in plasma oxytocin levels and these effects were, at least partially, antagonized by the corresponding subtype selective antagonists (-)pindolol (2 mg/kg) and ritanserin (2 mg/kg), respectively, administered 10 min before 8-OH-DPAT (0.5 mg/kg) or DOI (0.5 mg/kg). The maximal response to the 5-HT1A receptor agonists (approx. 120 nmol/l) was from 8 to 5 times the maximal response to the 5-HT2A C receptor agonist. In addition, 8-OH-DPAT and DOI caused a decrease in plasma CCK levels, whereas the 5-HT1B receptor agonist TFMPP gave rise to an increase in plasma CCK levels. There were no statistically significant effects by any of the 5-HT receptor agonists on plasma somatostatin or gastrin levels under the present conditions. It is suggested that the clinical effects of new anxiolytic 5-HT1A receptor agonists, such as buspirone, to an extent may be mediated via an increased release of oxytocin.
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PMID:Effects of 5-HT agonists, selective for different receptor subtypes, on oxytocin, CCK, gastrin and somatostatin plasma levels in the rat. 902 12


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