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)

In a recent study, we found a circadian rhythm in the response of central serotonin (5-HT)1A receptors to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In the present study, the 8-OH-DPAT-induced 5-HT behavioural syndrome was examined in rats kept under continuous dark (DD) conditions for 6 days. The results revealed a circadian rhythm in the behavioural response to 8-OH-DPAT under DD conditions. The pattern of this rhythm was similar to that observed under the light-dark conditions, except for the phase delay that corresponds to the period of free-running rhythm. These results strongly suggest that the rhythm in the function of central 5-HT1A receptors is driven by the endogenous oscillator.
Cell Mol Life Sci 1997 Mar
PMID:Circadian rhythm in the function of central 5-HT1A receptors is endogenous in nature. 910 84

The aim of our work is to investigate the potential involvement of serotonin and its G-protein-coupled receptors in neural differentiation or other developmental processes in Xenopus laevis. By using a RT-PCR strategy, we isolated a cDNA fragment from X. laevis brain showing high amino-acid similarity with the mammalian 5-HT1A receptor. We used this fragment to isolate a cDNA clone containing a single ORF of 408 amino-acids with an overall amino-acid identity of 73% with the human and rat 5-HT1A receptor. This structural similarity suggests that this clone encodes the Xenopus homolog of the mammalian 5-HT1A receptor (X5-HT1A). In order to establish a possible role for this receptor in development, we analyzed the pattern of its gene expression during embryogenesis, larval stages and in adult brain by in situ hybridization. The first signal of mRNA expression appears in the rostral part of brain stem at stage 22, when the first neurons start differentiation [38,21]. In later stages of development, the cells expressing X5-HT1A transcripts appear to correspond to serotonergic neurons. By stage 41, X5-HT1A mRNA is also detected in the inner nuclear layer (INL) of the developing retina. This pattern of expression is maintained until stage 46, i.e. at the beginning of metamorphosis. In adult, additional brain areas express X5-HT1A mRNA, particularly in telencephalon, diencephalon and mesencephalon. On the whole, our data show that the X5-HT1A receptor mRNA is developmentally regulated, with expression first appearing in differentiating serotonergic neurons, where this receptor may mediate, through an autocrine regulatory pathway, the trophic action of serotonin on developing serotonergic system.
Brain Res Mol Brain Res 1997 Jul
PMID:Cloning and developmental expression of 5-HT1A receptor gene in Xenopus laevis. 922 3

Serotonin (5-HT) was found to inhibit steroid (17 alpha,20 beta-dihydroxy-4-pregnen-3-one; 17,20 beta P)-induced resumption of oocyte meiosis (oocyte maturation) in vitro in the teleost Fundulus heteroclitus. Serotonin inhibited both follicle-enclosed and denuded oocytes, which indicates the presence of oocyte-associated 5-HT sensitive sites. The response of oocytes to 5-HT was characterized pharmacologically, i.e., the capacity of serotonergic agonists and antagonists to mimic or block the 5-HT inhibition of the steroid-induced oocyte maturation was assessed by the changes in the percentage of oocyte germinal vesicle breakdown (GVBD). Dose-response curves for each compound were drawn and compared. The rank order of potency among the agonists was: 5-HT > 5-methoxytryptamine > tryptamine = 5,6-diHT = 5-carboxidotryptamine > 5,7-diHT = 5-methoxy-dimethyltryptamine > alpha-methyl-5HT > 2-methyl-5HT. Incubation of ovarian follicles with high doses of some antagonists (mianserin and metergoline) induced oocyte GVBD, although this effect was associated with high levels of oocyte atresia during GVBD or shortly after maturation. Consequently, doses of the antagonist too low to induce GVBD were tested for their ability to block the 5-HT inhibitory action; the rank order of potency was: MDL-72222 = metoclopramide > metergoline > propanolol > ketanserin. Dopamine, acetylcholine, epinephrine, and norepinephrine could also inhibit 17,20 beta P-induced GVBD, although at doses much higher than those of 5-HT; melatonin and histamine had no effect on oocyte maturation. These results suggest that specific receptors mediate the inhibitory action of 5-HT on the steroid-triggered meiosis resumption. The pharmacological profile of these 5-HT receptors is different from those of any known mammalian 5-HT receptor, although they showed some similarities to the 5-HT1A, 5-HT2, and 5-HT3 receptors, as well as to 5-HT receptors on oocytes of some bivalve molluscs.
Mol Reprod Dev 1997 Oct
PMID:Pharmacology of the serotonergic inhibition of steroid-induced reinitiation of oocyte meiosis in the teleost Fundulus heteroclitus. 929 79

[35S]Guanosine-5'-O-(3-thio)triphosphate ([35S]GTPgammaS) binding to G proteins was measured by in vitro autoradiography in guinea pig and rat brain sections after activation by 5-hydroxytryptamine (5-HT) receptor agonists. 5-Carboxamidotryptamine stimulated binding strongly in hippocampus and lateral septum and weakly in substantia nigra. This effect was blocked in the substantia nigra by the 5-HT1B/1D receptor antagonist GR-127,935 and in the former two regions by the 5-HT1A antagonist NAN-190. 5-HT1B/1D receptor agonists stimulated binding in substantia nigra and in areas containing 5-HT1A receptors. In guinea pig substantia nigra, 5-(nonyloxy)-tryptamine maximally stimulated [35S]GTPgammaS binding by 54%, with an EC50 value of 62 nM; at 100 microM, this agonist increased binding by approximately 200% in hippocampus (with a 2-fold weaker EC50 value). The distribution of [3H]8-OH-DPAT binding sites was identical to that of the [35S]GTPgammaS labeling stimulated by the 5-HT1A agonist (R)-8-hydroxy-2-dipropylaminotetralin [(R)-8-OH-DPAT)]. (R)-8-OH-DPAT, (S)-8-OH-DPAT, and buspirone stimulated [35S]GTPgammaS binding in hippocampus by 340%, 140%, and 78%, with EC50 values of 71, 51, and 132 nM. Enhanced [35S]GTPgammaS binding was not detected in the presence of 5-HT1F, 5-HT2, 5-HT4, and 5-HT7 receptor agonists. Because activation of mu-opioid, muscarinic M2, histamine H3, and cannabinoid receptors was also visualized successfully, these data suggest that only receptors coupled to pertussis toxin-sensitive G proteins can be seen by [35S]GTPgammaS binding autoradiography. This study also shows that different 5-HT receptors coupled to these proteins can show a wide range of [35S]GTPgammaS binding stimulation. Although the functional significance of these variations is unclear, this technique offers advantages over receptor autoradiography because it does not require high affinity radioligands and provides a measure of agonist efficacies in various brain regions.
Mol Pharmacol 1997 Oct
PMID:5-Hydroxytryptamine1A and 5-hydroxytryptamine1B receptors stimulate [35S]guanosine-5'-O-(3-thio)triphosphate binding to rodent brain sections as visualized by in vitro autoradiography. 938 25

Differential immunohistochemical labeling is often observed using different antibodies against the same protein. Two polyclonal antipeptide antibodies against the 5-HT1A receptor have been generated by our group. The S1A-170 (aa 170-186) and 258 (aa 258-274) are specific for sites in the second extracellular loop and third intracellular loop, respectively [E.C. Azmtia, I. Yu, H.M. Akbari, N. Kheck, P.M. Whitaker-Azmitia and D.R. Marshak, Antipeptide antibodies against the 5-HT1A receptor, J. Chem. Neuroanat., 5 (1992) 289-298]. Comparison of the labeling patterns of these two antibodies and other antipeptide antibodies against the 5-HT1A receptor revealed that although similar populations of cells were labeled, individual antibodies favor certain staining patterns. Immunocytochemistry and western blotting results of transfected cell lines and brain tissue revealed the following: (1) both the S1A-170 and S1A-258 are specific for the 5-HT1A receptor when used for immunocytochemistry in transfected HEK-293 and COS-1 cells; (2) when expressed in cultured cell lines, the 5-HT1A receptor is differentially glycosylated dependent on cell type, and the S1A-258 is specific for only certain species on immunoblots; and (3) the S1A-258 and L5B7 [M. Riad, S. El Mestikawy, D. Derge, H. Gozlan, and M. Hamon, Visualization and quantification of central 5-HT1A receptors with specific antibodies, Neurochem. Int., 4 (1991) 413-423] label common bands at 40 and 70 kDa on immunoblots of hippocampal proteins, but show opposite staining intensities. These results provide evidence for the immunocytochemical specificity of both the S1A-170 and S1A-258 and suggest that the discrepancies noted in immunohistochemistry may be due in part to different molecular conformations.
Brain Res Mol Brain Res 1997 Oct 15
PMID:Molecular characterization of antipeptide antibodies against the 5-HT1A receptor: evidence for state-dependent antibody binding. 940 44

To investigate the receptor-channel coupling pathway, the coding region of the 5-HT1a receptor was subcloned into two plasmid vectors pSP64(polyA+) and pSP64T. Compared to the original 5-HT1a receptor construct G-21, both new constructs increased greatly the expression of functional 5-HT1a receptors in Xenopus oocytes, which developed large inward current responses to 5-HT. These responses were dose-dependent (EC50 approximately 150 nM), and could be elicited also by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The 5-HT1a receptor mediated current had an oscillatory time course, and a reversal potential close to the equilibrium potential for Cl- (ca. -25 mV). Moreover, during and for some minutes following the application of 5-HT, these oocytes acquired the property of generating a transient inward current when their membrane was hyperpolarized. These features are characteristic of responses mediated by other receptors (e.g. muscarinic, angiotensin, serum receptors, etc.) that are known to couple to the endogenous PLC/PI second messenger pathway in Xenopus oocytes. In particular, the 5-HT1a receptor mediated current was very similar to the current induced by 5-HT-stimulation of heterogenic 5-HT2c receptors. Our results show further that the 5-HT1a receptor couples to the endogenous PLC/PI pathway much less efficiently than the 5-HT2c receptor. These results demonstrate clearly that the human 5-HT1a receptor can couple efficiently to the Xenopus oocyte endogenous PLC/PI pathway, and provide additional evidence for cell-specific signal transduction.
Brain Res Mol Brain Res 1997 Nov
PMID:Efficient coupling of 5-HT1a receptors to the phospholipase C pathway in Xenopus oocytes. 942 13

Environmental enrichment augments neuronal plasticity and cognitive function and possible mediators of these changes are of considerable interest. In this study, male rats were exposed to environmental enrichment or single housing for 30 days. Rats from the enriched group had significantly higher 5-HT1A receptor mRNA expression in the dorsal hippocampus (62%, 59% and 44% increase in the CA1, CA2 and CA3 subfields, respectively). This was associated with significantly higher [3H]8-OH-DPAT binding in the inferior part of CA1. No changes were seen for 5-HT2A or 5-HT2C receptor mRNAs. The neuronal plasticity detected after environmental change may be mediated, in part, through 5-HT1A receptors.
Brain Res Mol Brain Res 1998 Jan
PMID:Environmental enrichment selectively increases 5-HT1A receptor mRNA expression and binding in the rat hippocampus. 947 97

The distribution of 5-HT1A receptor mRNA in the human brain was studied in neonatal, children and adult cases by means of in situ hybridization histochemistry, using an oligonucleotide derived from the coding region of the human receptor. A prenatal pattern of development was observed. The hippocampus, raphe nuclei and neocortex presented high levels of hybridization already at the fetal/neonatal stage, fully comparable to the adult. A high and transient hybridization signal was found in cerebellum. These results support a role for 5-HT1A receptors in the regulation of neural development.
Brain Res Mol Brain Res 1998 Sep 18
PMID:Early localization of mRNA coding for 5-HT1A receptors in human brain during development. 974 36

1. The serotonin type 1A (5-HT1A) receptors are members of a superfamily of seven transmembrane domain receptors that couple to GTP-binding regulatory proteins (G-proteins). We have studied the modulation of agonist binding to 5-HT1A receptors from bovine hippocampus by metal ions and guanine nucleotide. 2. Bovine hippocampal membranes containing the 5-HT1A receptor were isolated. These membranes exhibited high-affinity binding sites for the specific agonist [3H]OH-DPAT. 3. The agonist binding is inhibited by monovalent cations Na+, K+, and Li+ in a concentration-dependent manner. Divalent cations such as Ca2+, Mg2+, and Mn2+, on the other hand, show more complex behavior and induce enhancement of agonist binding up to a certain concentration. The effect of the metal ions on agonist binding is strongly modulated in the presence of GTP-gamma-S, a nonhydrolyzable analogue of GTP, indicating that these receptors are coupled to G-proteins. 4. To gain further insight into the mechanisms of agonist binding to bovine hippocampal 5-HT1A receptors under these conditions, the binding affinities and binding sites have been analyzed by Scatchard analysis of saturation binding data. Our results are relevant to ongoing analyses of the overall regulation of receptor activity for G-protein-coupled seven transmembrane domain receptors.
Cell Mol Neurobiol 1998 Oct
PMID:Metal ion and guanine nucleotide modulations of agonist interaction in G-protein-coupled serotonin1A receptors from bovine hippocampus. 977 53

The literature describing the expression of 5-HT receptor subtypes by astrocytes is controversial and incomplete. It is clear that primary cultures of astrocytes express receptors of the 5-HT2 family coupled to phospholipase C and of the 5-HT7 receptor family positively coupled to adenylyl cyclase. Cultured astrocytes have also been reported to express receptors of the 5-HT1 family, although the exact subtypes present are unknown. In the present study we have investigated which of the known rat G-protein coupled 5-HT receptor mRNAs are expressed by cultured astrocytes. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed expression of 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5B, 5-HT6 and 5-HT7 receptor mRNAs in astrocytes derived from 2-day old rats and cultured for 10-12 days. Messenger RNAs for 5-HT4 and 5-HT5A receptors were not detected. The functional expression of 5-HT1 receptor subtypes was investigated by measuring the ability of 5-HT1 receptor agonists: 8-OH-DPAT (5-HT1A receptors), RU24969 (5-HT1A, 5-HT1B, 5-HT1D, and 5-HT1F receptors) or sumatriptan (5-HT1B, 5-HT1D, and 5-HT1F receptors) to modulate forskolin or isoproterenol stimulated cAMP production. These compounds, at concentrations up to 10 microM, did not significantly attenuate cAMP production. These results indicate that although astrocytes express mRNA for each of the five 5-HT1 receptor subtypes which have been isolated from the rat, these receptors are not coupled to the inhibition of adenylyl cyclase.
Brain Res Mol Brain Res 1998 Oct 30
PMID:Cultured astrocytes express messenger RNA for multiple serotonin receptor subtypes, without functional coupling of 5-HT1 receptor subtypes to adenylyl cyclase. 979 56


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