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)

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) increases plasma glucose levels in conscious rats probably by stimulation of central 5-HT1A receptors. We have examined the effects of WAY100135 (N-tert-butyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenylpropan amide), a selective 5-HT1A receptor antagonist and its enantiomers on plasma glucose levels and on the hyperglycaemia induced by 8-OH-DPAT. (R,S)-WAY100135 (minimum effective dose (MED) 3 mg/kg i.v.) and (S)-WAY100135 (MED 1 mg/kg i.v.) dose-dependently attenuated 8-OH-DPAT-induced hyperglycaemia. In contrast, (R)-WAY100135 at doses up to 3 mg/kg i.v. was unable to block hyperglycaemia induced by 8-OH-DPAT. When the antagonists were examined for intrinsic effects on plasma glucose levels only (S)-WAY100135 (3 mg/kg i.v.) caused a significant but transient hyperglycaemia (20% increase). These results are consistent with previous suggestions that (R,S)-WAY100135 and (S)-WAY100135 are selective 5-HT1A receptor antagonists and that 8-OH-DPAT-induced hyperglycaemia is mediated by 5-HT1A receptors. The antagonist action of WAY100135 is stereoselective, and more potent activity being observed with the (S) enantiomer.
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PMID:Effects of the selective 5-HT1A receptor antagonist WAY100135 and its enantiomers on 8-OH-DPAT-induced hyperglycaemia in conscious rats. 820 9

Stable expression of neuronal receptors in cell lines of neural origin is important for studies of neurotransmitter mediated signal transduction. We have achieved this for the first time in three cell lines which are derived from various tissues of neural origin (hippocampus, HN2; chinese hamster brain explant, NCB-20; rat dorsal root ganglion, F-11). Following electroporation assisted transfer of a construct containing the hippocampal serotonin 5-HT1A receptor (5-HT1AR) DNA, one neural cell line, NG-108-15 (murine neuroblastoma x C6 glioma), failed to express the transfected activity, while three others as well as the non-neural CHO (chinese hamster ovary) cells expressed high levels of the receptor. Upon normalization to coexpressed human beta-hexosaminidase B activity, it was found that the human 5-HT1AR, which is normally concentrated in the hippocampus and at a lesser density in the brain, was expressed at the highest level (15.7 x 10(4) receptors/cell) in the HN2 followed by the NCB-20 (8.3 x 10(4) receptors/cell), F-11 (4.4 x 10(4) receptors/cell) and lastly the non-neuronal CHO (4.2 x 10(4) receptors/cell) cells. Ten-twelve days after passage, a striking increase in expression of the receptor was observed only in the cell lines of neural origin. By contrast, there was no appreciable increase in expression of the transfected 5-HT1AR in the non-neural CHO cells over time. This late increase in expression was eliminated in cells which had been maintained in low glucose (1 g/L) for the first two days after passage, thus establishing a vital role of glucose in expression of the transfected 5-HT1AR in cell lines of neural origin. In all cases the 5-HT1AR was negatively coupled to adenylate cyclase, as evidenced by an agonist mediated decrease in prostaglandin E1 stimulated cyclic AMP levels.
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PMID:Heterologous expression of the serotonin 5-HT1A receptor in neural and non-neural cell lines. 847 11

We have recently shown that the mitogenic effect of serotonin (5-hydroxytryptamine, 5-HT) on human small lung carcinoma (SCLC) cells is at least partly due to stimulation of a 5-HT1D receptor type. We now report that the 5-HT1A receptor agonist R(+)-8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT) is also capable of stimulating [3H]thymidine incorporation into SCLC GLC-8 cells, although with lower efficacy than 5-HT. The simultaneous administration of maximal doses of 8-OH-DPAT and the 5-HT1D receptor agonist sumatriptan reproduced the maximal [3H]thymidine incorporation observed with 5-HT alone. The 5-HT1A receptor antagonists spiperone and SDZ 216-525 completely abolished the effect of 8-OH-DPAT (IC50 30 nM for both drugs) behaving as pure antagonists. Accordingly, the two drugs partially inhibited the mitogenic effect of 5-HT. These data indicate that the mitogenic effect of 5-HT in SCLC cells involves both 5-HT1A and 5-HT1D receptor types.
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PMID:Mitogenic effect of serotonin in human small cell lung carcinoma cells via both 5-HT1A and 5-HT1D receptors. 856 73

Male Sprague-Dawley rats were given one of the 5-HT receptor agonists 8-OH-DPAT (0.5-2.0 mg kg-1), TFMPP (0.125-2.0 mg kg-1), DOI (0.125-2.0 mg kg-1), and m-CPBG (1.25-20.0 mg kg-1), selective for 5-HT1A, 5-HT1B, 5-HT2 and the 5-HT3 receptors, respectively, or one of the DA receptor agonists bromocriptine (2.0-32.0 mg kg-1), quinpirole (0.5-8.0 mg kg-1) and 7-OH-DPAT (0.2-3.2 mg kg-1), selective for DA D2, DA D2/D3 and DA D3 receptors, respectively. An additional group of animals was given buspirone (2.0-8.0 mg kg-1) a 5-HT1A receptor agonist and DA D2 receptor antagonist. Separate groups of rats were given both the 5-HT1A receptor antagonist pindolol and 8-OH-DPAT or both the DA D2/D3 receptor antagonist raclopride and 7-OH-DPAT. Blood samples were collected 30 min (in some cases 120 min) after drug administration and assayed for insulin, glucagon and glucose levels. The 5-HT1A receptor agonist 8-OH-DPAT produced a statistically significant decrease in plasma insulin levels and an increase in glucose, whereas glucagon levels were unaffected. The only effect observed after buspirone treatment was a small increase in plasma glucose levels. No significant effects on plasma insulin, glucagon or glucose were seen after treatment with the 5-HT1B, 5-HT2 or 5-HT3 agonists. The DA D3 receptor agonist 7-OH-DPAT produced a decrease in plasma insulin (3.2 mg kg-1, 120 min) and an increase in glucose levels. Administration of the DA D2/D3 receptor agonist quinpirole resulted only in increased plasma glucose, whereas the DA D2 receptor agonist bromocriptine had no effect. In support of a separate mediation of glucose secretion by 5-HT1A and DA D3 receptors, the effects of 8-OH-DPAT on glucose levels were antagonized by (-)pindolol pretreatment, and the 7-OH-DPAT-induced effects on glucose levels were antagonized by raclopride pretreatment. It is concluded that plasma glucose levels are under separate serotonergic and dopaminergic control, exerted via 5-HT1A and DA D3 receptors, respectively.
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PMID:Effects of selective serotonin and dopamine agonists on plasma levels of glucose, insulin and glucagon in the rat. 867 15

In the stress-induced hyperthermia (SIH) paradigm in mice, both a benzodiazepine receptor agonist, diazepam, and a 5-HT1A receptor agonist, flesinoxan, reduced the stress-induced increase in rectal temperature. The SIH procedure itself enhanced plasma ACTH and corticosterone levels but not plasma glucose levels. Diazepam (3, 6, and 12 mg/kg p.o.) did neither affect basal plasma ACTH, corticosterone, or glucose levels, nor did it suppress the stress-induced rises in these parameters. Flesinoxan (1, 3, and 10 mg/kg p.o.) enhanced plasma ACTH and corticosterone concentrations under nonstress conditions but did not affect the stress-induced increases in ACTH and corticosterone secretion. No clear effects of flesinoxan on plasma glucose levels were found. Our results indicate that in mice the anxiolytic effects of diazepam and flesinoxan in the SIH paradigm are not paralleled by a blockade of stress-induced increases in plasma ACTH, corticosterone, and glucose levels.
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PMID:Neuroendocrine effects of diazepam and flesinoxan in the stress-induced hyperthermia test in mice. 872 65

The functional effects of serotonin (5-HT) drugs and toxins on regional cerebral metabolic rates for glucose (rCMRglc) have been determined in rats with the in vivo, quantitative, autoradiographic [14C]2-deoxyglucose technique. Serotonin agents produced rCMRglc patterns different and more specific that one would predict from binding studies. At low doses 5-HT1 agonists reduced rCMRglc in limbic areas and at high doses increased rCMRglc in brain motor regions. The 5-HT2 agonists dose-dependently decreased rCMRglc in proencephalic areas and increased it in thalamic nuclei. 5-HT3 receptor antagonism resulted in rCMRglc decreases in limbic, auditory and visual areas and agents with 5-HT3 receptor activity increased rCMRglc in brain regions with high 5-HT3 receptor densities. Serotonin anxiolytics (e.g. azapirones) and antidepressants (e.g. tryciclic and non-tryciclic 5-HT reuptake inhibitors) reduced rCMRglc selectively in limbic areas and in brainstem monoaminergic nuclei. Dose, time from administration, receptor affinity, behavioral and neurochemical correlates, 5-HT system lesion and circulating glucocorticoid were all relevant factors in determining the rCMRglc effects of 5-HT drugs. Acutely neurotoxic amphetamines markedly increased rCMRglc in brain regions such as the nucleus accumbens that are thought to mediate amphetamine reinforcing properties; on the long term, toxic or electrolytic lesions or chronic treatment with 5-HT agonists produced minimal rCMRglc alterations in spite of marked and persistent changes in 5-HT function. In lesioned or chronically treated rats, acute challanges with 5-HT and non 5-HT agonists demonstrated specific deficits that were not detected in a resting state. Serotonin neuromodulation has been studied in humans by using positron emission tomography with 15O-water. Sequential measurements of regional cerebral blood flow (rCBF) were obtained during combined pharmacological challange with the 5-HT1A agonist buspirone and cognitive activation. Buspirone increased a memory related rCBF activation in task specific regions. This technique can provide a strong theoretical basis for the understanding of 5-HT drug mode of action in normal human brain and in neuropsychiatric diseases. Brain metabolism studies in animals will still be needed to elucidate the factors (e.g. pharmacokinetic and pharmacodynamic) relevant to the cerebral response to 5-HT drugs in humans.
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PMID:Cerebral metabolic effects of serotonin drugs and neurotoxins. 879 99

The effects of the serotonin1A(5-HT1A) receptor agonist buspirone on hypoglycemia elicited by tolbutamide were investigated in rats. Buspirone, at doses not affecting plasma glucose levels, inhibited the hypoglycemic effects of tolbutamide. The inhibitory effects of buspirone on tolbutamide-induced hypoglycemia were antagonized by the 5-HT1A receptor antagonist pindolol. As tolbutamide is known to induce hypoglycemia by facilitating insulin release, the effects of buspirone on a tolbutamide-induced increase in serum insulin levels were also studied. However, buspirone did not affect tolbutamide-induced insulin release. Adrenodemedullation inhibited the effects of buspirone. These results suggest that buspirone inhibits tolbutamide-induced hypoglycemia mediated by the 5-HT1A receptor, and adrenaline release may be involved in the effects of buspirone.
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PMID:The effects of the serotonin1A receptor agonist buspirone on tolbutamide-induced hypoglycemia in rats. 884 28

To determine whether emotional stress-induced rises in stress hormone levels are mediated by activation of 5-HT1A receptors, we studied the effects of the selective 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY-100635) on plasma ACTH, corticosterone, prolactin, and glucose levels in the conditioned ultrasonic vocalisation (USV) model in adult rats. The effects of WAY-100635 on USVs were also investigated in this paradigm. WAY-100635 (0.3, 1, and 3 mg/kg SC) had no clear effects on basal plasma ACTH, corticosterone, and glucose levels, but the 3 mg/kg dose significantly increased the plasma prolactin levels. The increases in plasma ACTH, corticosterone, and prolactin levels induced by the USV procedure were not affected by WAY-100635. This indicates that the 5-HT1A receptor does not play a major role in the distress-induced activation of the hypothalamic-pituitary-adrenal axis and prolactin secretion. The USVs were significantly enhanced by low doses of WAY-100635 (0.03 and 0.3 mg/kg SC), whereas higher doses (1.0 and 3.0 mg/kg SC) had no effect. These findings suggest that blockade of 5-HT1A receptors during stress may enhance the behavioural stress-response.
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PMID:The 5-HT1A receptor is not involved in emotional stress-induced rises in stress hormones. 895 69

We previously reported a significant mitogenic effect of serotonin (5-hydroxytryptamine, 5-HT) on human small-cell lung carcinoma cells (SCLC, GLC-8), mediated by both 5-HT1D and 5-HT1A receptors. Here we investigate possible interactions between the two receptor subtypes. Dose-effect curves obtained by simultaneously applying equipotent concentrations of the selective 5-HT1A agonist 8-OH-DPAT and the selective 5-HT1D receptor agonist sumatriptan are shifted to the right, although maximal effects are additive. The nonselective 5-HT antagonist metergoline displays higher potency when both receptor subtypes are activated. The 5-HT1D receptor antagonist GR127935 is markedly more potent against sumatriptan than against the sensitive portion of 5-HT effect. Indeed, both GR127935 and the 5-HT1A antagonist spiperone shift the EC50 for the residual effect of 5-HT from approximately 300 to 120-150 nM, suggesting that blocking one receptor subtype may facilitate activation of the other. Preincubation with either 8-OH-DPAT or sumatriptan suppresses the mitogenic response to the other specific receptor agonist; suppression is complete within 10 min at 37 degrees C, and is not observed when the preincubation is done at 4 degrees C. Measurements of adenylate cyclase activity do not help in interpreting the results. Conversely, measurements of MAP kinase activity reveals biphasic activation with a delayed activation at 1 h, and reproduce the suppression of the effect of the second drug by 15 min preincubation. These findings constitute the first evidence of a reciprocal negative interference between human 5-HT1A and 5-HT1D receptors, and indicate that SCLC GLC-8 cells simultaneously express both receptor subtypes. Mere reciprocal antagonism of the drugs employed cannot account for these data. We suggest that in this cell system cross-talk occurs in the transduction pathways of the two receptor subtypes.
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PMID:Evidence for receptor subtype cross-talk in the mitogenic action of serotonin on human small-cell lung carcinoma cells. 901 44

Serotonergic agents in general and the 5-HT1A agonist 8-OH DPAT in particular, reduce alcohol intake in rats and primates but the mechanism of this effect is not known. Previous studies have shown a correlation between alcohol consumption and the propensity to consume sweet substances. Indeed, certain biochemical events accompanying glucose utilization have been proposed as satiety signals in the control of feeding. Since 8-OH DPAT produces hyperglycemia, we tested the hypothesis that its effect on alcohol intake may be partly mediated through an increase blood glucose. Male Wistar rats were trained to drink a bout of 6% (w/v) alcohol using the limited access procedure which offers a daily 40-min access to alcohol and water. On consecutive test trial days separated by intervening non-drug days, the amount of alcohol consumed (1 g/kg on intervening days) was measured following the administration of 8-OH DPAT (150 micrograms/kg 10 min prior to drinking) alone or in combination with the prior (20 min) injection of idazoxan (2 mg/kg), an alpha-2 adrenoceptor antagonist with hypoglycemic properties. Idazoxan attenuated the hyperglycemic effect of 8-OH DPAT and completely reversed 8-OH DPAT's inhibitory effect on alcohol intake. Idazoxan alone produced a mild hypoglycemia and stimulated alcohol intake. These results support a role for glucoregulatory processes in serotonergically-mediated changes in alcohol consumption.
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PMID:The reduction in alcohol intake by the 5-HT1A agonist 8-OH DPAT and its attenuation by the alpha 2 adrenergic antagonist idazoxan correlates with blood glucose levels. 934 84


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