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)

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

Previously, it has been shown that, in small doses, putative 5-HT1A receptor agonists selectively increase ingestion of hypertonic saline without affecting either water or isotonic saline intake. Evidence was obtained in the present series of experiments for selective reduction in hypertonic saline following the administration of a variety of serotonergic directly- and indirectly-acting agonists. Water, isotonic saline (0.9%), or hypertonic saline (1.8%) were made available to separate groups of water-deprived rats. The results indicated some selectivity with the 5-HT-uptake inhibitor and releaser d-fenfluramine and the 5-HT uptake inhibitor fluoxetine, and with the 5-HT agonists mCPP [1-3-chlorophenyl)piperazine] and MK 212 [6-chloro-2-(1-piperazinyl)pyrazine]. In each case, hypertonic intake was significantly suppressed. Distinct from these compounds were TFMPP [1-(3-(trifluoromethyl)phenyl)piperazine], RU 24969 [5-methoxy-3-(1,2,3,6-tetrahydropyridinyl)1H-indole], and quipazine. This second group either reduced fluid intake indiscriminately or reduced water and isotonic saline drinking. Selective reduction in the intake of hypertonic saline did not occur. Finally, peripheral-administration of 5-HT or the 5-HT1B agonist CGS 12066B [7-trifluoromethyl-4(4-methyl-1-piperazinyl-pyrolo) (1,2-a) 1:2 maleate], had no significant effect on fluid intake in any fluid condition. The results are discussed in terms of a possible serotonergic mechanism which may underlie inhibition of hypertonic salt drinking, and which involves mediation through a subtype of the 5-HT1 receptor.
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PMID:Selective reduction by serotonergic agents of hypertonic saline consumption in rats: evidence for possible 5-HT1C receptor mediation. 250 54

The effects of serotonin receptor agonists and antagonists on the electrically (3 Hz) evoked 3H overflow were determined on pig brain cortex slices preincubated with 3H-serotonin and superfused with physiological salt solution containing indalpine (an inhibitor of serotonin uptake) plus phentolamine. The potencies of the serotonin receptor agonists and antagonists were compared with their affinities for 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT1D binding sites in pig or rat tissue membranes; in addition, the potencies of the agonists were compared to their potencies in inhibiting adenylate cyclase activity in membranes of calf substantia nigra. In the superfusion experiments on pig brain cortex slices the following rank orders of potencies were obtained: agonists, serotonin greater than 5-methoxytryptamine = 5-carboxamidotryptamine greater than RU 24969 (5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole) greater than SDZ 21009 (4(3-terbutylamino-2-hydroxypropoxy)indol-2-carbonic-acid-isopr opylester) greater than or equal to yohimbine greater than or equal to cyanopindolol greater than 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) greater than or equal to CGS 12066 B (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline); ipsapirone and urapidil were ineffective; antagonists (antagonism determined against 5-methoxytryptamine as an agonist), metitepine greater than metergoline greater than mianserin. Propranolol, spiperone or mesulergine did not produce a shift of the concentration-response curve for 5-methoxytryptamine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pharmacological properties of the presynaptic serotonin autoreceptor in the pig brain cortex conform to the 5-HT1D receptor subtype. 279 14

Male rats were adapted to a 22 hr water-deprivation schedule, and to a 30 min test of hypertonic (1.8 or 2.7%) NaCl solution ingestion. A novel benzodiazepine, Ro23-0364, recently reported to have anxiolytic activity in rats and squirrel monkeys but to have limited potential to produce unwanted side effects, produced significant dose-related increases in hypertonic saline ingestion. Midazolam, a benzodiazepine full agonist, increased salt intake but the effect was offset at higher doses by the induction of sedation. Three putative 5-HT1A agonists, proposed as nonbenzodiazepine-related anxiolytics, were also tested: the highly selective 8-OH-DPAT, gepirone and ipsapirone (TVX Q 7821). In each case, occasions when hypertonic saline consumption was significantly increased were detected. At 300 micrograms/kg of 8-OH-DPAT and 10 mg/kg of gepirone, the appearance of a pronounced flattened body posture effectively interfered with drinking responses. It appears possible that a behavioural action shared by benzodiazepines and 5-HT1A agonists may be responsible for the increased hypertonic saline ingestion.
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PMID:Benzodiazepines and putative 5-HT1A agonists increase hypertonic saline consumption in rehydrating rats. 282 18

Previous reports indicate that 5-HT1A agonists, in addition to benzodiazepines, increase the consumption of hypertonic saline in rehydrating rats. Experiment 1 investigated the effects of 8-OH-DPAT (10-100 micrograms/kg) and gepirone (0.1-3.0 mg/kg) on consumption of water and of saline over a range of concentrations (0.45%-2.8%) in a 30 min drinking test. The two 5-HT1A agonists dose-dependently increased ingestion of two hypertonic salt solutions, but produced little or no increase in the drinking of water, hypotonic or isotonic saline. Experiment 2 demonstrated that 8-OH-DPAT and gepirone did not enhance water consumption in animals given a water preload, or markedly increase drinking quinine-adulterated water. Taken together, the results indicate a selective dose-related effect of the two drugs to increase hypertonic saline drinking; they did not have a general hyperdipsic effect across all salt and water conditions, and they did not increase intake simply because of a low baseline level of consumption. Hence, 5-HT1A agonist act much more selectively than benzodiazepines in their effects on drinking responses.
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PMID:Specific effect of putative 5-HT1A agonists, 8-OH-DPAT and gepirone, to increase hypertonic saline consumption in the rat: evidence against a general hyperdipsic action. 297 13

Electrophysiological techniques were used to study the effects of various serotonin (5-HT) agonists and antagonists on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) of rats. Systemic administration of the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1.25-80 micrograms/kg i.v.) increased the firing rate of the majority (75%) of DA cells studied and stimulated their bursting activity. A subpopulation (25%) of DA neurons was inhibited by 8-OH-DPAT. Selective lesions of 5-HT neurons by the neurotoxin 5-7-dihydroxytryptamine abolished completely the excitatory effect of 8-OH-DPAT on both firing rate and bursting activity of DA neurons. Microiontophoretic application of 8-OH-DPAT into the VTA did not cause any change in the firing rate of DA neurons. Treatment with the selective 5-HT1B agonist CGS 12066B (7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrolo[1,2-a] quinoxaline 1:2 maleate salt) (1.25-160 micrograms/kg i.v.) did not cause any change in basal firing rate of VTA DA cells. Systemic administration of trifluoromethylphenylpiperazine (TFMPP) (1.25-160 micrograms/kg i.v.) and m-chlorophenylpiperazine (mCPP) (1.25-320 micrograms/kg i.v.), two mixed 5-HT1B/5-HT1C receptor agonists, significantly reduced the firing rate of all VTA DA neurons studied. The effect of mCPP (maximal inhibition, 40%) was more pronounced compared to that of TFMPP (maximal inhibition, 25%). Microiontophoretic application of mCPP into the VTA caused a marked inhibition of the basal activity of DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin-dopamine interaction in the rat ventral tegmental area: an electrophysiological study in vivo. 796 60

To study interactions between DA and 5-HT neurochemical systems in the DA D1 supersensitized induction of oral activity in neonatal 6-hydroxydopamine (6-OHDA) lesioned rats, the effects of a variety of 5-HT receptor agonists and antagonists were determined. At 3 days after birth rats were treated with desipramine HCl (20 mg/kg i.p., base form) 1 h before 6-OHDA HBr (100 micrograms, salt form, in each lateral ventricle). When these rats were studied as adults it was determined that the striatal content of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was reduced by 98%, while the striatal content of 5-HT was elevated by 75%. The Bmax and Kd for [3H]SCH 23390 and [3H]spiperone binding to striatal homogenates was unaltered in the lesioned rats. However, oral activity responses to a D1 agonist (SKF 38393), D2 antagonist (spiperone) and 5-HT1C agonist [1-(3-chlorophenyl)piperazine] were enhanced several fold in the lesioned rats. Several other agonists and antagonists that act at 5-HT1A, 5-HT1B, 5-HT2 and 5-HT3 receptors did not produce an altered response in the lesioned rats, nor were these substances effective in attenuating m-CPP-enhanced oral activity responses. The DA D1 receptor antagonist, SCH 23390 HCl (0.30 mg/kg i.p.), did not attenuate the response to m-CPP 2HCl (1.0 mg/kg i.p.). However, the 5-HT receptor antagonist, mianserin HCl (1.0 mg/kg s.c.) did effectively attenuate the oral activity response to SKF 38393 HCl (1.0 mg/kg i.p.). These findings indicate that there is supersensitization of both DA D1 and 5-HT1C receptors in neonatal 6-OHDA-lesioned rats, and that a D1 agonist acts via the 5-HT1C receptors. Therefore, induction of oral activity by DA agonists occurs through a serotoninergic neurochemical system.
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PMID:Serotonin (5-HT) systems mediate dopamine (DA) receptor supersensitivity. 831 65

Twenty-two-hour water-deprived rats were divided into two groups: The first was given access to 1.8% saline and water in a 30-min two-choice test; the second was given access to 0.9% saline and water in the same type of intake preference test. Animals were tested following administration of several selective 5-hydroxytryptamine1 (5-HT1) receptor agonists. The results indicated a clear-cut distinction between the effects of selective 5-HT1A receptor agonists, on the one hand, and putative 5-HT1B/1C agonists on the other. Ipsapirone, gepirone, and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) all showed evidence of increasing the consumption of 1.8% saline (less preferred to water) but had no effect on intake of the more preferred 0.9% saline. In contrast, 1-3-(chlorophenyl)piperazine (mCPP) and 1-(3-(trifluoromethyl)phenyl)piperazine (TFMPP) (5-HT1B/1C agonists) reduced intake of 1.8 and 0.9% saline in the two tests. One interpretation of these results is to assume that the 5-HT1A agonists act at inhibitory autoreceptors to diminish central serotonergic activity, while mCPP and TFMPP act postsynaptically to enhance serotonergic activity. The possibility is discussed that mCPP and TFMPP may act to increase the perceived salt concentration during drinking, whereas the 5-HT1A agonists may have the opposite effect.
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PMID:Effects of selective 5-HT1 receptor agonists in water-deprived rats on salt intake in two-choice tests. 833 10

Northern blotting studies have demonstrated mRNA for the serotonin 5-HT1A receptor in human neonatal kidney (B. K. Kobilka, T. Frielle, S. Collins, T. Yang-Feng, T. S. Kobilka, U. Francke, R. J. Lefkowitz, and M. G. Caron. Nature Lond. 329: 75-79, 1987). To confirm expression of receptor protein in kidney, we raised antibodies to two peptides derived from the third intracellular loop of the human 5-HT1A receptor. Specific immunoglobulin G (IgG) was purified sequentially on protein A-Sepharose and peptide-Affigel 10 columns. Each IgG was able to: 1) quantitatively immunoprecipitate [3H]8-OH-2-(di-n-propylamino)1,2,3,4-tetrahydronaphthalene ([3H]8-OH-DPAT)-labeled human and rat receptors; 2) immunoblot a new protein in cells transfected with human 5-HT1A receptor DNA; and 3) immunoautoradiographically label areas of rat brain (frontal cortex, hippocampus, and lateral septum) in a highly characteristic pattern similar to that labeled by 125I-Bolton-Hunter-8-methoxy-2-(N-propyl-N-propylamino)Tetralin, a specific 5-HT1A receptor autoradiography ligand. By use of a light microscopic immunoperoxidase labeling technique, incubation of each IgG antibody with sections of rat and human kidney demonstrated an identical pattern of immunoreactivity. Specific labeling of basolateral plasma membranes was detected throughout medullary and cortical thick ascending limbs (TAL), in distal convoluted tubules (DCT), in connecting tubule cells of the connecting tubule, and in principal cells of the initial collecting tubule. There was no labeling in the inner medulla, glomeruli, or blood vessels. The labeling was blocked by preincubation with the corresponding peptide, but not with noncorresponding peptide or carrier protein. There was no labeling with preimmune IgG. Electron microscopic immunoperoxidase labeling confirmed the specific localization of the IgG antibody along the basolateral plasma membrane in all positively staining cells in rat kidney. Radioligand binding studies with the specific 5-HT1A receptor ligand [3H]8-OH-DPAT confirmed the presence of 5-HT1A receptor binding sites in bulk-isolated rat medullary TAL. These studies provide the first evidence that the 5-HT1A receptor is expressed on the basolateral surface of TAL and DCT cells of human and rat kidney. The specific localization to these cells suggests a possible role for the 5-HT1A receptor in the regulation of salt and water transport in mammalian kidney.
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PMID:Immunohistochemical mapping of cellular and subcellular distribution of 5-HT1A receptors in rat and human kidneys. 843 Aug 34

In segments of human right atrial appendages preincubated with [3H]noradrenaline and superfused with physiological salt solution containing desipramine and corticosterone, we determined the effects of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on tritium overflow evoked by transmural electrical stimulation (2 Hz). Tritium overflow was inhibited by 5-HT, 5-carboxamidotryptamine (5-CT), 5-methoxytryptamine (5-MeOT), 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole succinate (RU 24969) and sumatriptan. Yohimbine and oxymetazoline (in the presence of idazoxan) also inhibited tritium overflow. The inhibitory potency of the drugs was significantly correlated with their affinity for 5-HTID receptors in human brain and for cloned human 5-HT1D alpha and 5-HT1D beta receptors, but not with their affinity for 5-HT1B, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5A, 5-HT5B and 5-HT7 receptors. The potency order 5-CT > 5-HT > 5-MeOT is opposite to the order of affinities reported for 5-HT6 binding sites. The preferential 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetraline (up to 0.3 microM) and the selective 5-HT4 receptor agonist cisapride (up to 1 microM) failed to inhibit tritium overflow. L-694,247, a potent 5-HT1D beta receptor agonist, did not inhibit tritium overflow, but counteracted the inhibitory effect of 5-HT. Ketanserin at a concentration which should block 5-HT1D alpha but not 5-HT1D beta receptors and methiothepin at a concentration which may be assumed to block both 5-HT1D alpha and 5-HT1D beta receptors antagonized the inhibitory effect of 5-HT. Propranolol and ondansetron did not modify the 5-HT-induced inhibition of release. In conclusion, noradrenaline release in human right atrial appendages is inhibited via 5-HT receptors which are located on the noradrenergic axon terminals. These inhibitory presynaptic 5-HT receptors belong to the 5-HT1D subfamily. The ability of ketanserin to antagonize the inhibitory effect induced by activation of these receptors suggests that they can be subclassified as 5-HT1D alpha.
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PMID:Inhibition of noradrenaline release via presynaptic 5-HT1D alpha receptors in human atrium. 869 81


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