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 effects of drugs that bind selectively to different serotonin (5-HT) receptor subtypes were assessed in pigeons. Keypecking was maintained by a multiple fixed-ratio schedule of reinforcement in which responding also was punished during one component. The greatest increases in punished responding were produced by the buspirone analogs BMY 7378 and ipsapirone, which act at the 5-HT1A receptor. RU 24969, with high affinity for both 5-HT1A and 5-HT1B receptors, and 1-(2-methoxyphenyl)piperazine, a 5-HT1 compound, increased punished responding to a lesser extent, as did the 5-HT2 antagonists ketanserin and ritanserin. The 5-HT3 antagonists GR 38032F, ICS 205930 and MDL 72222 showed little systematic effect, and the mixed 5-HT1B/5-HT1C compound 1-(3-chlorophenyl)piperazine produced only decreases in punished responding. Levels of neurotransmitter metabolites in cerebrospinal fluid were assessed across a wide dose range of representative drugs used in the behavioral studies. Levels of the 5-HT metabolite 5-hydroxyindoleacetic acid were decreased significantly by BMY 7378 and ipsapirone, were not changed by ritanserin and were increased at one dose by MDL 72222. The results are consistent with suggestions that decreased 5-HT neurotransmission is involved in the effects of novel nonbenzodiazepine anxiolytics such as buspirone. Behavioral and neurochemical data also indicate that the effects of these drugs on other neurotransmitter systems do not play a significant role in their anxiolytic actions.
J Pharmacol Exp Ther 1989 Sep
PMID:Behavioral studies with anxiolytic drugs. VI. Effects on punished responding of drugs interacting with serotonin receptor subtypes. 247 47

Serotonin has no obvious effect on basal cyclic AMP levels but reduces the forskolin-, isoproterenol-, and vasoactive intestinal peptide-induced stimulation of cyclic AMP levels in a dose-dependent manner. Serotonergic, cholinergic, muscarinic, alpha-adrenergic, and dopaminergic antagonists have no effect on the serotonin response. Topical application of a serotonin/pargyline solution to the living eye causes desensitisation of the serotonin response in the iris-ciliary body, an observation confirming the presence of specific serotonergic receptors linked to adenylate cyclase. The 5-HT1A [5-hydroxytryptamine (serotonin) type 1A] receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin and buspirone mimic the serotonin response in reducing the forskolin-stimulated cyclic AMP levels, as do the indole derivatives 5-methoxytryptamine, 5-hydroxtryptophan, and tryptamine. However, the ineffectiveness of the 5-HT1A agonist ipsapirone and the inability of spiroxatrine to block the serotonin response show that classical 5-HT1A receptors are not involved. The serotonin response is blocked by pertussis toxin and is insensitive to the phosphodiesterase inhibitor theophylline, which indicates the involvement of an inhibitory guanine regulatory protein in the coupling of the serotonin receptor to the adenylate cyclase catalytic unit.
J Neurochem 1989 Sep
PMID:Evidence for the presence of serotonin receptors negatively coupled to adenylate cyclase in the rabbit iris-ciliary body. 254 97

The signal transduction pathways of the cloned human 5-HT1A receptor have been examined in two mammalian cell lines transiently (COS-7) or permanently (HeLa) expressing this receptor gene. In both systems, 5-hydroxytryptamine (5-HT, serotonin) mediated a marked inhibition of beta 2-adrenergic agonist-stimulated (80% inhibition in COS-7 cells) or forskolin-stimulated cAMP formation (up to 90% inhibition in HeLa cells). This serotonin effect (EC50 = 20 nM) could be competitively antagonized by metitepine and spiperone (Ki = 81 and 31 nM, respectively) and could also be blocked by pretreatment of cells with pertussis toxin. In both cell types, 5-HT failed to stimulate adenylyl cyclase through the expressed receptors. In HeLa cells, 5-HT also stimulated phospholipase C (approximately 40-75% stimulation of formation of inositol phosphates). Again, this effect was inhibited by metitepine. However, the EC50 of 5-HT was considerably higher (approximately 3.2 microM) than that found for inhibition of adenylyl cyclase. Both pathways were demonstrated to be similarly affected by pertussis toxin. These findings indicate that like the M2 and M3 muscarinic cholinergic receptors, the 5-HT1A receptor can couple to multiple transduction pathways with varying efficiencies via pertussis toxin-sensitive G-proteins. The lack of stimulation of cAMP formation by this 5-HT1A receptor may suggest the existence of another pharmacologically closely related receptor.
J Biol Chem 1989 Sep 05
PMID:Effector coupling mechanisms of the cloned 5-HT1A receptor. 254 39

The effects of chronic cortisol treatment on neuroendocrine and behavioral responses to serotonin1 (5-HT1) receptor agonists were studied in conscious, freely moving rats. Seven-day cortisol treatment (25 mg/kg/day with osmotic minipumps) markedly suppressed basal plasma corticotropin (ACTH) and corticosterone concentrations, indicating a suppression of the hypothalamo-pituitary-adrenocortical axis. Cortisol also decreased body weight, food intake, plasma norepinephrine (NE), and epinephrine (E) levels. In the drug challenge studies, we used two 5-HT1 agonists, the 5-HT1B and 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), and the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT), to examine the effect of cortisol on their behavioral and neuroendocrine effects. After 7-day cortisol treatment, plasma prolactin responses to both m-CPP and 8-OHDPAT were significantly decreased. While the plasma NE, E, and food intake responses to m-CPP were also significantly reduced by cortisol treatment, these same responses to 8-OHDPAT were unchanged. The effect of m-CPP on locomotor activity was also decreased. Since only the responses to m-CPP and 8-OHDPAT previously shown to be antagonized by pretreatment with the 5-HT1/5-HT2 antagonist, metergoline, were significantly attenuated after cortisol treatment, these changes may be specific to 5-HT receptors. These data indicate that chronic exposure to high glucocorticoid levels alters 5-HT1 receptor-mediated functions and provides additional evidence relevant to the contribution of glucocorticoid elevation to the symptoms of depression.
Neuroendocrinology 1989 Sep
PMID:Long-term cortisol treatment impairs behavioral and neuroendocrine responses to 5-HT1 agonists in the rat. 255 39

The effect of intra-hippocampal injections of the serotonergic 5-HT1A receptor agonist, buspirone, on rat exploratory activity was evaluated in the 'open field' and 'elevated plus maze' tests. The dose of 2.5 micrograms, but not of 1 microgram, of buspirone administered to the dentate gyrus of the hippocampus increased the time spent on exploration of open arms in the elevated plus maze, as well as it increased the number of central entries in the open field. The results indicate an anti-emotional influence of local stimulation of 5-HT1A receptors by buspirone.
Eur J Pharmacol 1989 Sep 22
PMID:Intra-hippocampal buspirone in animal models of anxiety. 257 36

DOI (1-100 micrograms/kg i.v.) induced an increase in mean blood pressure in the anaesthetized rat. Similarly, in the pithed rat, DOI (1-100 micrograms/kg i.v.) induced a dose-dependent increase in mean blood pressure, as did 5-HT. However, in contrast to 5-HT, DOI did not change the heart rate in either intact or pithed rats. In the pithed rat, the dose-pressor response curves to both 5-HT and DOI were unaffected by MDL 72222 (5-HT3 receptor antagonist), spiroxatrine or (+/-)-pindolol (5-HT1A receptor antagonists), idazoxan (alpha 2-adrenoceptor blocking agent) and AR-C 239 (alpha 1-adrenoceptor blocking agent). Only the selective 5-HT2 receptor antagonist. LY 53857, significantly and dose dependently shifted to the right the dose-response curves to both 5-HT and DOI. These results indicated that DOI possesses 5-HT2 agonistic properties and that the pressor response induced by DOI in the pithed rat is mediated via 5-HT2 receptors.
Eur J Pharmacol 1989 Sep 22
PMID:Characterization of DOI, a putative 5-HT2 receptor agonist in the rat. 258 42

Our work has been concerned with the role of high affinity serotonin receptors in regulating the development of the serotonergic system. In previous studies, we have found evidence that these receptors occur on astroglial cells and that their number is developmentally linked. The current work is aimed at investigating the mechanism by which these receptors may regulate serotonin neuronal growth. Primary cultures of astroglial cells were exposed to serotonin (5-HT) or the selective receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-D-PAT, for 5-HT1a receptors) or trifluoro-methyl-phenyl-piperazine (TFMPP) and m-chlorophenylpiperazine (mCPP) (for 5-HT1b receptors). Media was collected after 4 or 24 h, and added to primary cultures of serotonergic neurons. Growth was determined by specific uptake of radiolabeled serotonin into the cultures. Our results show the presence of a factor(s) in the glial-conditioned media which can be stimulatory or toxic to serotonin neurons, depending on the neuronal plating density. This factor is significantly present after 24 h, is found in both brainstem and cortical astroglial-conditioned media and appears to be linked to the 5-HT1a receptor. Thus, it appears possible that the serotonergic neuronal system can regulate its own development through an action on astroglial cells.
Brain Res 1989 Sep 11
PMID:Stimulation of astroglial serotonin receptors produces culture media which regulates growth of serotonergic neurons. 279 Apr 58

Extracellular single-unit recordings were made from serotonergic dorsal raphe neurons in chloral hydrate anesthetized male Sprague-Dawley rats. Buspirone, a clinically effective non-benzodiazepine anxiolytic drug, caused inhibition of firing of these neurons when given by intravenous (ED50 = 0.011 mg/kg, i.v.), intraperitoneal (ED50 = 0.088 mg/kg, i.p.), and intragastric (effective dose = 1.0-20.0 mg/kg, i.g.) injection. Buspirone also inhibited these cells when it was administered to the outside of recorded neurons by microiontophoresis (effective currents = 2-15 nA). Iontophoretically applied buspirone did not potentiate nor block the effects of iontophoretically applied GABA. Systemic administration of two putative buspirone metabolites (1,2-pyrimidinyl piperazine and 5-hydroxy buspirone) in relatively high doses had a weak effect and no effect, respectively, on dorsal raphe neuronal firing. It is concluded that buspirone potently and directly inhibits the firing of serotonergic dorsal raphe neurons in the rat. Since buspirone inhibits the firing of serotonergic dorsal raphe neurons and binds to 5-HT1A receptors, the present study supports the notion that central serotonergic systems may be involved in the therapeutic effects of anxiolytic drugs.
Eur J Pharmacol 1986 Sep 23
PMID:Inhibition of serotonergic dorsal raphe neurons by systemic and iontophoretic administration of buspirone, a non-benzodiazepine anxiolytic drug. 287 3

The ability of the beta-adrenoceptor antagonist propranolol to block the effects of serotonin (5-HT) and 5-HT1A-selective agonists on the spontaneous firing of serotonergic dorsal raphe neurons was assessed. During microiontophoretic application, (-)- but not (+)-propranolol rapidly and reversibly blocked the suppressant effects of the 5-HT1A-selective agonists ipsapirone (TVX Q 7821) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). However, (-)-propranolol was a relatively weak antagonist of 5-HT itself, suggesting that the endogenous neurotransmitter may have actions on dorsal raphe neurons in addition to those mediated by 5-HT1A receptors.
Eur J Pharmacol 1986 Sep 09
PMID:(-)-Propranolol blocks the inhibition of serotonergic dorsal raphe cell firing by 5-HT1A selective agonists. 287 17

Using iontophoretic techniques we observed that in vivo isapirone (TVX Q 7821), a selective ligand for the 5-HT1A binding site, at low ejection currents (5-30 nA) antagonised 5-HT and 8-hydroxy-2-(di-n-propylamino) tetralin (DPAT)-induced suppression of hippocampal unit activity, with little effect on baseline firing rate itself. At higher ejection currents (20-100 nA) or following prolonged application, isapirone inhibited unit firing. Responses to GABA were unaffected by isapirone. These data demonstrate that isapirone is a 5-HT1A receptor antagonist with partial agonist properties on 5-HT sensitive neurones in the rat hippocampus.
Eur J Pharmacol 1987 Sep 23
PMID:Isapirone is a partial agonist at 5-hydroxytryptamine 1A (5-HT1A) receptors in the rat hippocampus: electrophysiological evidence. 288 11


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