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)

Prolactin secretion is controlled by the hypothalamus through different neurotransmitters which interact with multiple receptor subtypes. The discovery of different families of receptors for serotonin (5-HT1-5-HT7) and excitatory aminoacids (NMDA, KA, AMPA and metabotropic receptors) ilustrates the complexity of this regulation. Moreover, in the rat the role of different neurotransmitters changes during pubertal development. Present experiments were carried out to analyse the interactions between AMPA and serotoninergic receptors in the control of prolactin secretion in prepubertal male rats. For this purpose, 16 and 23-day old male rats were treated with 5-hydroxytryptophan (5-HTP, precursor of serotonin synthesis) plus fluoxetine (blocker of serotonin reuptake), 8-OH-DPAT (agonist of 5-HT1A receptors), DOI and alpha-Me-5-HT (agonists of 5-HT2 receptors), 1-phenylbiguanide (agonist of 5-HT3 receptors) alone or in combination with AMPA (agonist of AMPA receptors). The results obtained indicate that: (a) activation of 5-HT1A receptors stimulated PRL secretion on day 16 and inhibited it on day 23; activation of 5-HT2 receptors stimulated PRL secretion on days 16 and 23, whereas activation of 5-HT3 receptors inhibited PRL release only on day 23; (b) activation of AMPA receptors inhibited PRL secretion on day 23, but not on day 16 and (c) a cross-talk is apparent between 5-HT2 and AMPA receptors in the regulation of PRL secretion, the stimulatory effect of DOI being blocked by AMPA.
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PMID:Interactions between serotoninergic and aminoacidergic pathways in the control of PRL secretion in prepubertal male rats. 1180 Feb 86

The present study investigated whether serotonin (5-HT) agonists could inhibit the ability of arginine-vasopressin (AVP) to induce a form of scent marking called flank marking by their actions in the medial preoptic-anterior hypothalamus (MPOA-AH). DOI, a 5-HT2A,2B,2C receptor agonist, did not inhibit AVP-induced flank marking, but mCPP a 5-HT2A antagonist and 5-HT2B,2C agonist inhibited AVP-induced flank marking. In addition, the finding that 8-OH-DPAT, CGS-12066A and SC53116 also inhibited AVP-induced flank marking suggests that 5-HT could also inhibit flank marking by acting through 5-HT1A, 5-HT7, 5-HT1B and/or 5-HT4 receptor subtypes. These data support the hypothesis that 5-HT acts within the MPOA-AH to inhibit the ability of AVP to induce flank marking.
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PMID:Serotonin and vasopressin interact in the hypothalamus to control communicative behavior. 1200 93

Effects of 5-hydroxytryptamine (5-HT) on EPSPs and EPSCs in the rat dorsolateral septal nucleus (DLSN) were examined in the presence of GABA(A) and GABA(B) receptor antagonists. Bath application of 5-HT (10 microm) for 5-10 min increased the amplitude of the EPSP and EPSC. (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (10 microm), an agonist for 5-HT1A and 5-HT7 receptors, did not facilitate the EPSP. alpha-Methyl-5-HT (10 microm), a 5-HT2 receptor agonist, increased the amplitude of the EPSC. Alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine (10 microm) and 6-chloro-2-(1-piperazinyl)pyrazine (10 microm), selective 5-HT2B and 5-HT2C receptor agonists, respectively, had no effect on the EPSP. The 5-HT-induced facilitation of the EPSP was blocked by ketanserin (10 microm), a 5-HT2A/2C receptor antagonist. However, N-desmethylclozapine (10 microm), a selective 5-HT2C receptor antagonist, did not block the facilitation of the EPSP induced by alpha-methyl-5-HT. The inward current evoked by exogenous glutamate was unaffected by 5-HT. 5-HT (10 microm) and alpha-methyl-5-HT (10 microm) increased the frequency of miniature EPSPs (mEPSPs) without changing the mEPSP amplitude. The ratio of the paired pulse facilitation was significantly decreased by 5-HT and alpha-methyl-5-HT. The 5-HT-induced facilitation of the EPSP was blocked by calphostin C (100 nm), a specific protein kinase C (PKC) inhibitor, but not by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (10 microm), a protein kinase A inhibitor. Phorbol 12,13-dibutyrate (3 microm) mimicked the facilitatory effects of 5-HT. These results suggest that 5-HT enhances the EPSP by increasing the release of glutamate via presynaptic 5-HT2A receptors that link with PKC in rat DLSN neurons.
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PMID:Activation of presynaptic 5-hydroxytryptamine 2A receptors facilitates excitatory synaptic transmission via protein kinase C in the dorsolateral septal nucleus. 1219 74

In the present study, we have used in situ hybridization to examine the distribution of serotonin (5-HT) receptors in rat dorsal root ganglion (DRG) neurons. Within DRG neurons, mRNAs for 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT3B and 5-HT4 receptors were readily detected in small (<25 microm), medium (25-45 microm) and large (>45 microm) diameter neurons. In contrast mRNAs for 5-HT1A, 5-HT1E, 5-HT2C, 5-HT5A, 5-HT5B, 5-HT6 and 5-HT7 receptors were undetectable in these neurons. The present study provides an insight into the molecular profile of 5-HT receptor subtypes in neurons responsible for modulating sensory information.
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PMID:Serotonin receptor mRNA expression in rat dorsal root ganglion neurons. 1253 38

(1) The effects of the selective 5-HT7 receptor antagonists SB-269970 (3-300 microg kg-1; n=5-6) and SB-656104 (30 microg kg-1; n=5) administered centrally (i.c.v.) were investigated on the 'micturition reflex' in the urethane anaesthetized female rat. (2) In cystometric recordings, SB-269970 caused significant increases in volume of 58+/-15 and 138+/-33% and pressure of 140+/-46 and 149+/-60% thresholds at 10 and 30 microg kg-1. These changes were associated with significant decreases in distension-induced bladder contraction of 62+/-14 and 60+/-11%, respectively. However, there was no change in residual volume. At the higher doses, SB-269970 blocked the micturition reflex. SB-656104 had similar effects to SB-269970 but in addition significantly increased the residual volume. (3) SB-269970 (10 microg kg-1; n=5) given i.v. had no effect on the micturition reflex. (4) SB-269970 (30 microg kg-1; n=4) given intrathecally (i.t.) had no effect on micturition reflex, although the selective 5-HT1A receptor antagonist WAY-100635 given i.t. after SB-269970 caused a significant increase in the volume threshold. (5) Using an isovolumetric method in which urethral changes were measured, SB-269970 (30 microg kg-1; n=4; i.c.v.) failed to have any effect on these urethral-evoked changes although they significantly reduced the amplitude of the bladder contraction. (6) These data demonstrate that 5-HT7 receptors located supraspinally in the rat are involved in the control of micturition.
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PMID:Evidence for the involvement of central 5-HT7 receptors in the micturition reflex in anaesthetized female rats. 1296 34

Continuous infusions of 5-hydroxytryptamine (5-HT) inhibit the tachycardiac responses to preganglionic (C7-T1) sympathetic stimulation in pithed rats pretreated with desipramine. The present study identified the pharmacological profile of this inhibitory action of 5-HT. The inhibition induced by intravenous (i.v.) continuous infusions of 5-HT (5.6 microg x kg-1x min-1) on sympathetically induced tachycardiac responses remained unaltered after i.v. treatment with saline or the antagonists GR 127935 (5-HT1B/1D), the combination of WAY 100635 (5-HT1A) plus GR 127935, ritanserin (5-HT2), tropisetron (5-HT3/4), LY215840 (5-HT7) or a cocktail of antagonists/inhibitors consisting of yohimbine (alpha2), prazosin (alpha1), ritanserin, GR 127935, WAY 100635 and indomethacin (cyclooxygenase), but was abolished by methiothepin (5-HT1/2/6/7 and recombinant 5-ht5A/5B). These drugs, used in doses high enough to block their respective receptors/mechanisms, did not modify the sympathetically induced tachycardiac responses per se. I.v. continuous infusions of the agonists 5-carboxamidotryptamine (5-CT; 5-HT1/7 and recombinant 5-ht5A/5B), CP 93129 (r5-HT1B), sumatriptan (5-HT1B/1D), PNU-142633 (5-HT1D) and ergotamine (5-HT1B/1D and recombinant 5-ht5A/5B) mimicked the above sympatho-inhibition to 5-HT. In contrast, the agonists indorenate (5-HT1A) and LY344864 (5-ht1F) were inactive. Interestingly, 5-CT-induced cardiac sympatho-inhibition was abolished by methiothepin, the cocktail of antagonists/inhibitors, GR 127935 or the combination of SB224289 (5-HT1B) plus BRL15572 (5-HT1D), but remained unchanged when SB224289 or BRL15572 were given separately. Therefore, 5-HT-induced cardiac sympatho-inhibition, being unrelated to 5-HT2, 5-HT3, 5-HT4, 5-ht6, 5-HT7 receptors, alpha1/2-adrenoceptor or prostaglandin synthesis, seems to be primarily mediated by (i). 5-HT1 (probably 5-HT1B/1D) receptors and (ii). a novel mechanism antagonized by methiothepin that, most likely, involves putative 5-ht5A/5B receptors.
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PMID:Pharmacological profile of the 5-HT-induced inhibition of cardioaccelerator sympathetic outflow in pithed rats: correlation with 5-HT1 and putative 5-ht5A/5B receptors. 1450 36

To investigate the role of serotonin (5-HT) receptor 1A or 7 in regulating lordosis behavior in female rats, ovariectomized rats were treated with 3 kinds of receptor agonists and lordosis behavior was observed. The injected agents were the selective 5-HT1A receptor agonist, buspirone (BUS), the highly selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin ((+/-)8-OH-DPAT), and the 5-HT1A and 5-HT7 receptor agonist, (R)-8-hydroxy-2-(di-n-propylamino)tetralin ((+)8-OH-DPAT). A behavioral test was performed after ovariectomy and subcutaneous implantation of a silicon tube containing estradiol. Female rats in which the lordosis quotient (LQ) was over 70 were intraperitoneally injected with several doses of these agents. As a result, in the BUS group, the dose of 3 mg/kg bw, but not 1 mg/kg was effective for suppressing lordosis. On the other hand, an inhibitory effect was observed from 0.25 mg/kg and 0.5 mg/kg in the (+)8-OH-DPAT and (+/-)8-OH-DPAT groups, respectively. In the time-course experiment, in all drug-treated groups, LQ decreased to lower than 20 after 15 min and low LQ continued for 1 hr at least. Measurement of locomotor activity using an infrared sensor system showed no relation between the decrease in lordosis by these agents and spontaneous locomotion. These results indicate that 5-HT1A is strongly involved in the lordosis-inhibiting circuit of the serotonin neurons.
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PMID:Effects of highly or relatively selective 5-HT1A receptor agonists on lordosis in female rats. 1457 74

Neurons in the suprachiasmatic nucleus (SCN), the site of the endogenous biological clock in mammals, fire spontaneously, peaking in firing rate near ZT6 or at the midpoint of the light phase in a 12:12 light-dark cycle. In rat hypothalamic slices, tissue incubations with drugs can produce a shift in this daily rhythm, the magnitude of which is dependent upon dose and the time of treatment. Previous work with 8-OH-DPAT had noted its ability to produce a phase advance, an earlier occurrence of the peak in neuronal firing, when applied at ZT6. Activation of 5-HT7 receptors was thought to be responsible for the shift, despite the clear preference of 8-OH-DPAT for 5-HT1A sites in terms of receptor binding affinity. In the present work, the actions of 8-OH-DPAT in SCN slices were confirmed and expanded to include additional dose-response and antagonist treatments. By itself, 8-OH-DPAT produced a concentration-dependent phase advance that was sensitive to co-application with 5-HT7 antagonists (ritanserin, mesulergine, SB-269970), but not to 5-HT1A antagonists (WAY-100,635, UH-301). Assignment of the receptor mechanisms for the antagonists employed was accomplished in experiments measuring binding affinities and the generation of cAMP, the latter monitored in a HEK-293 cell line expressing the r5-HT7 receptor and in tissue derived from rat SCN. The results indicate that the increases observed in cAMP levels are small but appear to be sufficient to produce a pharmacological resetting of the clock pacemaker. By aiding in the identification of the 5-HT receptor subtype responsible for the observed phase shifts and cAMP changes, 8-OH-DPAT represents an important pharmacological tool for 5-HT7 receptor activation, essentially broadening its role as the prototypical 5-HT1A agonist to one combining these two receptor activities.
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PMID:8-OH-DPAT as a 5-HT7 agonist: phase shifts of the circadian biological clock through increases in cAMP production. 1465 97

We have re-screened the genes for the 5-HT1A, 5-HT2A, 5-HT2C, and 5-HT7 serotonin receptors for genetic variants in a large African-American and Caucasian-American population sample. We have identified eight novel variants in these genes including four that are predicted to cause amino acid substitutions. These variants are additional candidates for association studies of behavioral disorders such as depression and schizophrenia as well as quantitative personality traits. We have also detected some, but not all, previously identified variants in these genes suggesting that many previously identified variants are unique to specific populations. The results of this study, and previous screens of serotonin receptors, demonstrate that the genes for serotonin receptors display marked population and molecular genetic complexity. These levels of complexity may have a substantial effect on genetic association studies of human behavioral variability related to these genes. We discuss the implications of these findings and propose methods to address complexity in genetic association studies.
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PMID:Re-screening serotonin receptors for genetic variants identifies population and molecular genetic complexity. 1468 23

Animals were submitted to an associative learning task named Pavlovian/instrumental autoshaping (P/I-A) and treated with selective 5-HT1A and 5-HT7 receptor agonists and antagonists. Next, they were sacrificed, their brains removed, dissected and changes on cortical and hippocampal cyclic adenosine monophosphate (cAMP) production were determined. Results revealed that, the 8-OH-DPAT treatment facilitated memory consolidation of autoshaping and that effect was blocked completely by WAY100635 and partially by DR4004. WAY100635 or DR4004 alone had no effect on autoshaping. The cAMP results were complex and yielded no clear relationship to the memory results. Thus, cortical and hippocampal increased on cAMP production was observed following administration of the 5-HT(1A/7) agonist 8-OH-DPAT. The memory effect was, completely or partially, reversed by the selective antagonists WAY100635 (5-HT1A) or DR4004 (5-HT7), respectively.
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PMID:8-OH-DPAT facilitated memory consolidation and increased hippocampal and cortical cAMP production. 1468 58


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