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 5-HT receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) produced dose-dependent increases in plasma adrenocorticotropin (ACTH) in the male rat by activation of 5-HT1A and 5-HT2 receptors respectively. The ACTH response to DOI was enhanced by repeated administration of electroconvulsive shock (five over 10 days) but abolished by the tricyclic antidepressant, amitriptyline (20 mg/kg for 14 days). In contrast 21 days lithium treatment failed to alter DOI-induced ACTH release. Neither repeated electroconvulsive shock, nor amitriptyline, nor lithium altered the ACTH response to 8-OH-DPAT. These data are consistent with results from ligand binding and behavioural studies which suggest that the sensitivity of brain 5-HT2 receptors is increased by repeated electroconvulsive shock but attenuated by tricyclic antidepressant treatment. In contrast, our data suggest that the antidepressant treatments studied do not alter the sensitivity of the 5-HT1A receptors involved in ACTH release.
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PMID:Selective 5-HT1A and 5-HT2 receptor-mediated adrenocorticotropin release in the rat: effect of repeated antidepressant treatments. 133 74

Several classes of drugs that modify serotonin (5-HT) neurotransmission are either currently used, or are being evaluated for their potential use in the treatment of anxiety, schizophrenia, and depression. 5-HT1A agonists are considered potential anxiolytics, while some atypical antipsychotics are potent 5-HT2 antagonists (and also have modest dopamine D2 affinity). Furthermore, there is a diverse group of serotonergic drugs that may be effective antidepressants. Secretion of ACTH, corticosterone/cortisol, prolactin, renin, oxytocin and vasopressin are stimulated by activation of different 5-HT receptor subtypes, while other neurotransmitter receptors also influence the secretion of these hormones. We compared the receptor binding profiles of 5-HT anxiolytics, antipsychotics and antidepressants with their endocrine effects. These comparisons could aid in understanding both the therapeutic and side effects of these drugs.
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PMID:Endocrine and receptor pharmacology of serotonergic anxiolytics, antipsychotics and antidepressants. 135 27

Evidence suggests that activation of 5-HT1A receptors leads to inhibition of 5-HT2-mediated behavior. The purpose of this study was to investigate the interaction between 5-HT1A and 5-HT2 receptor-mediated hormone secretion. Rats were pretreated with the 5-HT1A agonists buspirone (0, 0.5, 2.0 mg/kg, i.p.), 8-OH-DPAT (0, 0.05, 0.2 mg/kg, s.c.) or ipsapirone (0, 1.0, 2.5 mg/kg, i.p.), 45 min before decapitation. The 5-HT2 agonist DOI was administered (0-10 mg/kg, i.p.) 15 min after injection of the 5-HT1A agonists. The three 5-HT1A agonists differentially altered the DOI-induced increase of concentrations of hormone in plasma. None of the three 5-HT1A agonists influenced the basal levels of renin, ACTH and prolactin but 8-OH-DPAT and buspirone increased the basal level of corticosterone in plasma. Also, 8-OH-DPAT increased the effects of DOI on the concentration of ACTH in plasma but ipsapirone and buspirone did not. None of the 5-HT1A agonists significantly affected DOI-induced increase of concentration of corticosterone in plasma. Buspirone and 8-OH-DPAT potentiated the effect of DOI on prolactin in plasma, but ipsapirone did not. Ipsapirone potentiated the effect of DOI on the concentration of renin in plasma but this effect was not observed in 8-OH-DPAT- and buspirone-pretreated rats. The results do not support the hypothesis for a functional interaction between 5-HT1A and 5-HT2 receptors, since the three 5-HT1A agonists did not have the same influence on the hormonal effects of DOI.
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PMID:Neuroendocrine responses to the serotonin2 agonist DOI are differentially modified by three 5-HT1A agonists. 135 39

Previous studies have shown that activation of the 5-HT1A receptor subtype enhances rat plasma ACTH concentration. Such receptors have been suggested to be located on CRH neuronal cell bodies in the paraventricular nuclei of the hypothalamus (PVN). In this report, microinjection of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a selective 5-HT1A agonist, into the PVN increased rat plasma ACTH concentration in a dose-related manner. Similar responses were observed when two other 5-HT1A agonists, busipirone and gepirone, were used. (+/-)-Pindolol, known to have 5-HT1A antagonist properties, blocked the effect induced by an optimal dose of 8-OH-DPAT after injection into the PVN. This same dose of 8-OH-DPAT also induced a decrease of hypothalamic CRH concentration, which was completely antagonized as well by pretreatment injection of (+/-)-pindolol into the PVN. A significant inverse correlation was found between hypothalamic CRH and plasma ACTH levels. These results confirm that elevation of the plasma ACTH concentration induced by 5-HT1A receptor subtype activation is mediated by the release of CRH from the paraventricular nuclei of the hypothalamus in rats, but do not exclude other mechanisms.
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PMID:Activation of 5-HT1A receptor subtype in the paraventricular nuclei of the hypothalamus induces CRH and ACTH release in the rat. 136 87

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.
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PMID:The 5-HT receptor--G-protein--effector system complex in depression. I. Effect of glucocorticoids. 164 69

ACTH-(1-24) decreased the binding of the dopamine D2 receptor agonist, [3H]N-propylnorapomorphine ([3H]NPA), to rat striatal membranes in a concentration-dependent manner, with a Ki of 5 x 10(-7) M. Saturation curves for [3H]NPA binding in the presence of increasing concentrations of ACTH-(1-24) were performed. Scatchard analysis in the presence of ACTH-(1-24) revealed an increased dissociation constant (Kd), while the binding capacity (Bmax) was not affected by the peptide, suggesting an apparent competitive interaction between ACTH-(1-24) and [3H]NPA. ACTH-(1-24) also reduced the binding of the dopamine D2 receptor antagonist [3H]spiperone to striatal membranes, with a Ki of 10(-6) M. Much higher concentrations of ACTH-(1-24), up to 10(-4) M, were needed for the displacement of appropriate radiolabelled ligands from dopamine D1 receptors, serotonin 5-HT1A, serotonin 5-HT1B, muscarinic M1 acetylcholine and histamine H1 receptors. ACTH-(1-24) also inhibited the binding of [3H]spiperone to dopamine D2 receptors in membranes of the pituitary gland, the septum and the substantia nigra. ACTH-(1-39) and most ACTH fragments and analogs were less potent than ACTH-(1-24) in displacing [3H]NPA from the dopamine D2 receptor in striatal membranes. In general there was a relationship between displacing potency and chain length. ACTH-(7-16)-NH2 and benzyloxycarbonyl-ACTH-(8-16)-NH2, however, were more potent than ACTH-(1-24) in reducing the binding of [3H]NPA to dopamine D2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ACTH/MSH-like peptides inhibit the binding of dopaminergic ligands to the dopamine D2 receptor in vitro. 168 Jul 21

Fluoxetine (FLX) is a selective serotonin (5-HT) reuptake inhibitor with therapeutic benefit in patients with obsessive-compulsive disorder (OCD). To evaluate the effect of chronic FLX treatment on 5-HT1A receptor responsivity, hypothermic, neuroendocrine, and behavioral responses to the selective 5-HT1A receptor ligand ipsapirone (IPS) were examined in patients with primary OCD. A single dose of 0.3 mg/kg of IPS or placebo were given under double-blind, random-assignment conditions to ten patients before and during FLX treatment. The ability of IPS to induce hypothermia and ACTH/cortisol release was significantly attenuated during chronic FLX as compared to the pretreatment IPS challenge. The behavioral effects of IPS, though minimal, were less pronounced during FLX treatment. While FLX was effective in reducing the severity of OC symptoms, no significant correlation between attenuation of 5-HT1A receptor-mediated functional measures and FLX-induced improvement in OC symptoms was detected. These findings are consistent with the development of adaptive hyporesponsivity of the 5-HT1A receptor-effector system complex possibly involving subsensitivity of the 5-HT1A receptor itself and/or decreased functional activity of the postreceptor signal transduction. Modulation of 5-HT1A receptor-effector system function may be critical to the antidepressant/anti-OC efficacy of 5-HT reuptake inhibitors.
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PMID:Long-term fluoxetine treatment decreases 5-HT1A receptor responsivity in obsessive-compulsive disorder. 168 17

The i.p. injection of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) caused hypothermia and increased the concentrations of serum corticosterone and plasma ACTH in mice. The effects of 8-OH-DPAT at a dose of 2 mg/kg but not of 0.2 mg/kg on the hormone levels were attenuated by pretreatment with p-chlorophenylalanine (pCPA) which depleted brain 5-HT by about 70%; the hypothermic effect of 8-OH-DPAT was, however, not prevented. Similar results were obtained with another 5-HT1A agonist, 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554).
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PMID:p-chlorophenylalanine attenuates the pituitary-adrenocortical response to 5-HT1A receptor agonists in mice. 169 45

Only 25 years ago, tobacco dependence was believed to be a simple overuse problem. Research in the last 5 years has demonstrated a much more complex and profound neurochemical and behavioral disorder. Nicotine receptors in the locus coeruleus and the midbrain mesolimbic dopaminergic system activate both arousal state and enhance cognitive functioning (locus coeruleus) and activate the brain's "pleasure center" (mesolimbic system). Pharmacologic treatments, which must be completely integrated into the behavioral treatment plan, alter these profound central nervous system nicotine effects. Currently the only agent with clear scientific evidence for treatment efficacy is nicotine itself. Available only in a transmucosally delivered ion-exchange resin as nicotine polacrilex (Nicorette), nicotine should soon be available in other delivery forms that will have different absorption kinetics: transdermal patch, nasal spray, and vapor inhaler. Other agents in various phases of preclinical and clinical evaluation include 5-HT1A partial agonists such as buspirone; alpha 2-noradrenergic agonists such as clonidine; tricyclics such as doxepin; serotonin re-uptake antagonists such as fluoxetine; ACTH; 5-HT2 antagonists such as ritanserin; central excitatory amino acid inhibitors such as kynurenate; and calcium channel blockers.
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PMID:Pharmacologic approaches to smoking cessation. 174 93

The effects of 5-HT1A receptor agonists such as 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), BP-554 and buspirone on the serum corticosterone level were significantly more pronounced in female than in male mice. A similar sex difference was observed for the effect of 8-OH-DPAT on the plasma ACTH level. Pretreatment with proadifen, an inhibitor of microsomal drug-metabolizing enzymes, did not affect the sex difference in the effect of 8-OH-DPAT. The corticosterone response to 8-OH-DPAT in female mice was attenuated by ovariectomy. The effect of 8-OH-DPAT in ovariectomized mice was enhanced by chronic estradiol and the enhancement was blocked by testosterone. In male mice the corticosterone response to 8-OH-DPAT increased at 5 weeks after castration but had not changed at 2 weeks. Chronic estradiol enhanced the corticosterone response to 8-OH-DPAT in castrated mice. There was no difference between sexes in [3H]8-OH-DPAT binding to membranes and in the contents of 5-HT and 5-hydroxyindoleacetic acid in the hypothalamus. Accumulation of 5-hydroxytryptophan after decarboxylase inhibition in the hypothalamus was however greater in female than in male mice.
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PMID:Gonadectomy changes the pituitary-adrenocortical response in mice to 5-HT1A receptor agonists. 183 34


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