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)

A wide range of both prescription and nonprescription drugs has been reported to affect human sexual functioning. While the sexual side effects resulting from drug use have often been attributed to adrenergic, anticholinergic or dopaminergic activity, the present review considers the potential role of serotonin. Based on animal studies, serotonin has been shown to either facilitate or inhibit sexual activity depending on which serotonin receptor subtype is activated. However, few studies have been done in the human that assess the effects of drugs that bind selectively to serotonin receptors. Consequently, little is known about the role of serotonin in human sexual functioning. In this review, a wide range of drugs that affect both brain serotonergic systems and human sexual behavior is examined in an effort to determine the possible role of serotonin in human sexual behavior. A review of the literature is consistent with the hypothesis that the 5-HT1A and the 5-HT2 receptor subtypes play a facilitatory role in human sexual behavior. The evidence suggests that drugs that act as agonists on these receptor sites enhance sexual functioning in the human, while those that act as antagonists inhibit sexual functioning.
 ...
PMID:Psychoactive drugs and human sexual behavior: the role of serotonergic activity. 161 20

Hormonal modulation of neurotransmission emerged as a concept from the recognition that adrenocortical steroids exert profound effects at the level of receptors, G-proteins and effector units. G-proteins, a family of guanine nucleotide binding regulatory components that couple neurotransmitter receptors to various types of intracellular effector systems, appear to be a key target of glucocorticoid (GC) action in the CNS. It is thought that Gs/Gi mediates stimulation/inhibition of adenylate cyclase (AC system), which forms cyclic AMP as second messenger, while receptors stimulating phospholipase C do so through Go to produce two second messengers, inositol 1,4,5-triphosphate and diacylglycerol (PI system). Recent evidence suggests that GC increase Gs alpha-and decrease Gi alpha-protein subunit expression without affecting Go alpha. Activation of central pre- and postsynaptic 5-HT1A receptors which are linked to the Gi-AC complex, induces hypothermia and ACTH/cortisol release in rodents and humans. Compared with controls, patients with a major depressive disorder exhibit increased basal cortisol secretion associated with decreased hypothermic and ACTH/cortisol responses. The attenuated neuroendocrine and thermoregulatory response to 5-HT1A receptor activation may reflect a GC-dependent feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) system and subsensitivity of the presynaptic 5-HT1A-Gi-AC complex function. Differential regulation of 5-HT1A and 5-HT2 function leading to a relative 5-HT2-Go-PI complex supersensitivity may maintain HPA hyperactivity during the course of depression. These findings corroborate recent reports that GC, via GC-GC receptor (GR) complex activated promotion of gene transcription, modify the expression 5-HT1A-coupled Gi (but not 5-HT2-coupled Go) resulting in altered sensitivity of 5-HT1A-mediated signal transduction and further support the hypothesis of a differential regulation of 5-HT1A and 5-HT2 receptor function and a GC-GR/5-HT1A-G-protein--effector system-related abnormality in depression.
 ...
PMID:The 5-HT receptor--G-protein--effector system complex in depression. I. Effect of glucocorticoids. 164 69

The intravenous administration of 2-deoxy-D-glucose (2-DG) to conscious catheterised rats dose-dependently increased the levels of glucose in plasma throughout the analysis (60 min); the levels of insulin in plasma remained unchanged, except for an early significant decrease in rats treated with the largest dose (1 g/kg). Pretreatment (10 min beforehand) with the beta 2-adrenoceptor antagonist, ICI 118,551 (3 mg/kg) or the alpha 2-adrenoceptor antagonist, idazoxan (1 mg/kg) decreased the rise in levels of glucose in plasma elicited by 2-DG (250 mg/kg). Conversely, the alpha 1-adrenoceptor antagonist, prazosin (1 mg/kg) or the dopaminergic receptor blocker, haloperidol (0.5 mg/kg) amplified the hyperglycaemic response to 2-DG. Previous administration of either the 5-HT1A/5-HT2 receptor antagonist, spiperone (3 mg/kg), the 5-HT1/5-HT2 receptor antagonist, methysergide (1 mg/kg), the 5-HT1C/5-HT2 receptor antagonist, ritanserin (1 mg/kg) or the 5-HT3 receptor antagonist, ICS 205.930 (0.1 mg/kg) did not affect 2-DG-induced hyperglycaemia. On the other hand, the mixed 5-HT1A/5-HT1B/beta-adrenoceptor antagonist, (-)-propranolol (5 mg/kg) and the 5-HT1/5-HT2 receptor antagonist, methiotepin (1 mg/kg), respectively, diminished and amplified the hyperglycaemia elicited by 2-DG. Lastly, in rats pretreated with prazosin (1 mg/kg, 30 min beforehand), an additional pretreatment (10 min beforehand) with prazosin or methiotepin (both at 1 mg/kg) did not further amplify the hyperglycaemic response to 2-DG. These results indicate that 2-DG-induced hyperglycaemia is mediated by alpha 2- and beta 2-adrenoceptors and amplified by alpha 1-adrenoceptor blockade. Conversely, neither 5-HT1, 5-HT2 nor 5-HT3 receptors played a role in the hyperglycaemic response to 2-DG.
 ...
PMID:Influence of catecholaminergic and serotonergic receptor antagonists on the hyperglycaemic response to the neuroglucopaenic agent, 2-deoxy-D-glucose. 165 2

The biochemical and behavioural effects of isamoltane, a beta-adrenoceptor and 5-HT1B receptor antagonist that has higher affinity for 5-HT1B receptors than for 5-HT1A receptors, on 5-HT neurotransmission in the rat brain were examined. In binding experiments isamoltane was found to be about five times more potent as a ligand for the 5-HT1B receptor than for the 5-HT1A receptor (Ki values 21 and 112 nmol/l, respectively). Isamoltane increased the K(+)-evoked overflow of 3H from 3H-5-HT loaded slices of rat occipital cortex at 0.1 mumol/l, consistent with inhibition of the terminal 5-HT autoreceptor. In vivo, isamoltane significantly increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus and hippocampus indicating an increased 5-HT turnover with a maximal effect at 3 mg/kg s.c. A higher dose produced a less pronounced effect. This effect did not seem to be due to the beta-adrenoceptor blocking action of isamoltane since the beta-adrenoceptor antagonists. (-)-alprenolol, betaxolol or ICI 118.551 had no significant effects on 5-HT turnover at 5 mg/kg s.c. Isamoltane at 3 mg/kg s.c. induced the wet-dog shake response which was blocked by the tryptophan hydroxylase inhibitor p-chlorophenylalanine. In contrast, the same response induced by the 5-HT2 receptor agonist quipazine was not blocked by pretreatment with p-chlorophenylalanine. The wet-dog shakes evoked by isamoltane and quipazine were blocked by ritanserin, which indicates that 5-HT2 receptors are involved in their expression. These observations indicate that isamoltane, by inhibiting the terminal 5-HT autoreceptors, increased the synaptic concentration of 5-HT to a level that induced a behavioural response.
 ...
PMID:Biochemical and behavioural effects of isamoltane, a beta-adrenoceptor antagonist with affinity for the 5-HT1B receptor of rat brain. 167 59

In rats lightly restrained in horizontal cylinders, (+/-)-3,4-methylenedioxymethamphetamine (MDMA) dose dependently (0.16-10.0 mg/kg, s.c.) elicited spontaneous tail-flicks; that is, tail-flicks in the absence of extraneous stimulation. In contrast, amphetamine over a similar dose-range was inactive. Selective inhibitors of 5-hydroxytryptamine (5-HT) uptake and carrier-mediated 5-HT release, paroxetine and citalopram, did not induce spontaneous tail-flicks themselves and blocked those induced by MDMA. In distinction, maprotiline and bupropion, selective inhibitors of noradrenaline and dopamine uptake, respectively, failed to modify the action of MDMA. Spontaneous tail-flicks elicited by MDMA were unaffected by the selective 5-HT3 receptor antagonists, ICS 205,930 and GR 38032F. They were attenuated by the mixed 5-HT1/5-HT2 receptor antagonist, methiotepin, the mixed 5-HT1A/5-HT1B receptor antagonist, (-)-alprenolol and the mixed 5-HT1A/5-HT2 receptor antagonist, spiperone, but not by the selective 5-HT1C/5-HT2 receptor antagonists, ritanserin, ICI 169,369 and ketanserin. The novel 5-HT1A receptor antagonists, BMY 7378 and NAN-190, each abolished MDMA-evoked spontaneous tail-flicks. Selective D1, D2, alpha 1, alpha 2, beta 1 and beta 2 antagonists had little influence upon induction of spontaneous tail-flicks by MDMA. These data indicate that MDMA evokes spontaneous tail-flicks in the rat via a release of 5-HT which acts at 5-HT1A receptors. Thus, 5-HT1A receptors appear to be involved in the acute functional actions of MDMA.
 ...
PMID:Methylenedioxymethamphetamine induces spontaneous tail-flicks in the rat via 5-HT1A receptors. 167 9

Cocaine inhibits the 5-HT2-mediated (+/-)-DOI-induced head-twitch response (HTR) in mice in a dose-dependent manner. In order to investigate the possible inhibitory mechanism(s) of cocaine on 5-HT2 receptor function, we studied the effects of the selective adrenergic alpha 2 receptor antagonist yohimbine and the beta-adrenergic/5-HT1 receptor antagonist alprenolol, and the 5-HT3 antagonist ICS 205-930 on the inhibitory action of cocaine on the (+/-)-DOI-induced HTR. Neither yohimbine (0.1 and 0.5 mg/kg) nor alprenolol (10 mg/kg) pretreatment had any significant effect on the (+/-)-DOI-induced HTR. However, both antagonists prevented the inhibitory effects of cocaine on the (+/-)-DOI-induced HTR. The 5-HT3 antagonist ICS 205-930 neither produced HTR nor decreased the (+/-)-DOI-induced HTR frequency. The present results suggest that cocaine inhibits 5-HT2 receptor function by increasing the synaptic concentration of norepinephrine and serotonin via inhibition of their uptake and thus indirectly stimulating the respective inhibitory adrenergic alpha 2 and serotonergic 5-HT1A receptors. Furthermore, cocaine's 5-HT3 antagonist properties appear not to play a role in the inhibition of head-twitch behavior.
 ...
PMID:Inhibition of 5-HT2 receptor-mediated head-twitch response by cocaine via indirect stimulation of adrenergic alpha 2 and serotonergic 5-HT1A receptors. 167 73

Two approaches have been followed in attempting to elucidate the mechanisms of action of antidepressants. The first involves studies on the chronic effects of antidepressants and ECT on neurotransmitter receptor function in the rat brain. Such studies suggest that antidepressants decrease alpha 2 and beta-adrenoceptor function, increase alpha 1 receptor function, reduce 5-HT1A and dopamine autoreceptor function and increase GABA B function; changes also occur in 5-HT2 receptor function with antidepressants decreasing while ECT increases the activity of these receptors. The second approach involves studying platelets, lymphocytes and amine metabolites in the body fluids of depressed patients before and following effective treatment. Results of these studies suggest that while alpha-adrenoreceptors are largely unchanged, beta-receptors are increased and 5-HT2 receptors decreased in the depressed patient but normalise following effective treatment irrespective of the type of treatment. Such findings emphasize the importance of receptor adaptations in evaluating the mode of action of antidepressant treatments.
 ...
PMID:Antidepressants. Current concepts of mode of action. 167 87

The effect of continuous treatment with the selective 5-HT1A agonist gepirone upon 5-HT2-mediated behavior and cortical 5-HT2 receptor binding sites was examined in naive rats or rats receiving noradrenergic (DSP4) or serotonergic (5,7-DHT) lesions. Continuous administration of gepirone in non-lesioned rats for 3, 7, or 14 days enhanced the head shake response to the 5-HT agonist quipazine. This enhancement of 5-HT2-mediated behavior occurred despite concomitant down-regulation of cortical 5-HT2 binding sites. However, 28 days of gepirone administration significantly reduced behavioral responsiveness to quipazine. The gepirone-induced facilitation of 5-HT2-mediated behavior observed after 7 days of continuous treatment was blocked in both DSP4 and 5,7-DHT-lesioned rats. However, both noradrenergic and serotonergic denervation failed to modify the down-regulation of 5-HT2 receptor binding sites produced by continuous gepirone administration. These results suggest that the curious dissociation of behavioral and biochemical indices of 5-HT2 receptor function produced by continuous gepirone treatment may be the result of a dual yet separate action of the drug on central presynaptic noradrenergic and serotonergic mechanisms and postsynaptic 5-HT receptors. Furthermore, the postsynaptic action of gepirone which reduces the maximal number of cortical 5-HT2 receptor binding sites may be the result of gepirone's agonist action at postsynaptic 5-HT1A receptors.
 ...
PMID:Unique modulation of central 5-HT2 receptor binding sites and 5-HT2 receptor-mediated behavior by continuous gepirone treatment. 168 80

1. The effects of calcium antagonists on behaviour mediated by 5-hydroxytryptamine (5-HT) have been studied in rats and mice together with an investigation of the effects of these drugs on 5-HT synthesis in rat brain and endogenous 5-HT release from brain slices. 2. Administration of felodipine (35 mg kg-1 i.p.) to rats pretreated with tranylcypromine (20 mg kg-1, i.p.) resulted in the animals displaying the complete 5-HT-mediated behavioural syndrome (including head weaving, reciprocal forepaw treading and hind limb abduction) 75 min later. No evidence was obtained for the rate of 5-HT synthesis in brain regions differing between control and felodipine-treated rats. 3. Pretreatment with felodipine (10 or 35 mg kg-1) enhanced the 5-HT-mediated behavioural syndrome induced by injection of tranylcypromine and L-tryptophan. The rate of 5-HT accumulation in the brain was similar in both groups. Administration of Bay K 8644 (1 mg kg-1, i.p.) did not prevent the enhanced behaviour induced by felodipine (10 mg kg-1). 4. The 5-HT behavioural syndrome induced by injection of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was unaltered by either acute injection of felodipine (35 mg kg-1) or administration of felodipine twice daily for 3 days. 5. Felodipine (10 microM), verapamil (10 microM) and Bay K 8644 (10 microM) did not alter either basal release of endogenous 5-HT from slices prepared from frontal cortex or hind brain, or release following addition of K+ at a concentration of 20 mM, or 35 mM. 6. Verapamil (25mgkg-', i.p.), nicardipine (25mgkg-1, i.p.) and nifedipine (20mgkg-1, i.p.) all markedly inhibited the 5-HT2 receptor-mediated head twitch response in mice produced by injection of 5- methoxy-N,N-dimethyl-tryptamine (5-MeODMT). Felodipine had the same effect with an ED50 of 2.6mgkg-'. Bay K 8644 did not reverse this effect. Both verapamil (IC50:2.5 microM) and nicardipine (IC50:8 microM) were 5-HT2 antagonists as indicated by inhibition of [3H]-ketanserin binding in mouse frontal cortex. However felodipine and nifedipine antagonized 5-HT2 receptor binding only in the millimolar range.7. Hydralazine (5mg kg 1, i.p.) induced the 5-HT behavioural syndrome in tranylcypromine pretreated rats, enhanced the tranylcypromine/L-tryptophan behavioural syndrome, inhibited 5-MeODMT-induced head twitch behaviour in mice and was not a 5-HT2 receptor antagonist. 8. These data indicate that at a high dose, Ca2+ antagonists produce complex changes in 5-HT function in rodents which are similar to those produced by lithium administration. The data with hydralazine suggest that the effects seen are not related to an action at Ca2 + channels.
 ...
PMID:The effects of Ca2+ antagonists and hydralazine on central 5-hydroxytryptamine biochemistry and function in rats and mice. 169 44

1. The effects of serotonin (5-HT) on visually identified motoneurones were investigated using the whole-cell recording technique in a neonatal rat spinal cord slice preparation. 2. In current-clamp recordings, bath application of 5-HT depolarized motoneurones. This effect was observed after synaptic inputs were abolished by replacing external Ca2+ with Mg2+. 3. In voltage-clamp recordings at holding potentials of -70 to -90 mV, 5-HT induced an inward current (I5-HT) in motoneurones in a Ca2(+)-free-Mg2+ solution containing tetrodotoxin. This inward current was accompanied by an increase in membrane conductance, which was prominent at voltages negative to the holding potential. 4. The inward I5-HT response declined with repeated short applications of 5-HT. I5-HT produced by a single prolonged application (5 min) was only slightly diminished during the application period. 5. The minimum effective dose of 5-HT for initiating the inward I5-HT was less than 10 nM. At 10 microM, I5-HT approached maximal levels. The averaged dissociation constant (Kd) for 5-HT was approximately 120 nM. 6. Application of spiperone, the mixed 5-HT1A, 5-HT2 receptor antagonist, blocked the inward I5-HT. Application of (+)-8-OH-dipropylaminotetralin (8-OHDPAT), a 5-HT1A agonist, mimicked the action of 5-HT. 7. Various K+ channel blockers including tetraethylammonium chloride (30 mM), 4-aminopyridine (4 mM) and apamin (100 nM) did not abolish I5-HT. Application of extracellular Cs+ (10 mM) blocked I5-HT. 8. Peak inward I5-HT became larger with increasing extracellular K+. With low Cl- pipette solution (less than 1 mM), or in low extracellular Na+ solution (26 mM), the inward I5-HT was not abolished. 9. The current-voltage relation of I5-HT displayed inward rectification. In high external K+ concentration (20 mM), the reversal potential was about -29 mV, which is close to that of the inward rectifier evoked in motoneurones by membrane hyperpolarization. 10. The current generated by 5-HT displayed similar characteristics to the inward rectifying current induced in motoneurones by membrane hyperpolarization. It is thus suggested that the 5-HT-induced current is possibly mediated by the intrinsic inward rectifier conductance.
 ...
PMID:Direct excitation of rat spinal motoneurones by serotonin. 169 89


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>