Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotonin (5-hydroxytryptamine; 5-HT) has recently been shown to induce collagenase production in myometrial smooth muscle cells (Jeffrey et al. (1991) J. Cell. Physiol. 146, 399-406) by activating transcription of the collagenase gene (Wilcox et al. (1992) J. Biol. Chem. 267, 20752-20757) following an interaction with the 5-HT2 receptor (Rydelek-Fitzgerald et al. (1993) Mol. Cell. Endocrinol. 91, 67-74). These studies were performed to investigate factors controlling the regulation of 5-HT2 receptors in these cells. Northern blot analysis indicates that serotonin increases levels of 5-HT2 receptor mRNA in cells by approximately 4-fold. Detectable increases in mRNA levels occur within 2 h after administration of serotonin with maximal levels occurring after 12 h. The 5-HT2 receptor antagonists, ketanserin and spiperone, inhibit the serotonin-mediated increase in receptor mRNA. Selective 5-HT2 receptor agonists ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) and quipazine) mimic the effect of serotonin, whereas 5-HT1 and 5-HT3 receptor agonists ((+/-)-8-hydroxydipropylaminotetralin (8-OH-DPAT), 1-(3-chlorophenyl)piperazine dihydrochloride (mCPP), m-phenylbiguanide) have no effect. These data demonstrate that serotonin induces an increase in 5-HT2 receptor mRNA by interacting with the 5-HT2 receptor itself. Nuclear run-on analysis revealed that serotonin increases the initiation of 5-HT2 receptor mRNA synthesis. Moreover, the protein synthesis inhibitor, cycloheximide, prevents the induction of the mRNA for the receptor, demonstrating that serotonin-dependent increases in 5-HT2 receptor transcription require de novo protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin-mediated 5-HT2 receptor gene regulation in rat myometrial smooth muscle cells. 831 29

Recent studies have shown that serotonin (5-hydroxytryptamine; 5-HT) is required for the induction of interstitial collagenase in cultured rat and human myometrial smooth muscle cells. The present study was performed to determine which serotonin receptor subtype mediates the induction of collagenase in these cells. [125I]DOI ((+/- )-1-(2,5-dimethoxy-4-[125I]iodophenyl)-2-aminopropane), a 5-HT2 receptor agonist radioligand, bound specifically to sites in myometrial cell membranes, and exhibited binding characteristics essentially identical to those observed with brain 5-HT2 receptors. Radioligands selective for other serotonin receptor subtypes (5-HT1 and 5-HT3) failed to yield detectable binding. Northern blot analysis demonstrated the presence of 5-HT2 mRNA in the uterine smooth muscle cell cultures, whereas transcripts for 5-HT1A and 5-HT1C receptors were not detectable. Moreover, RT-PCR indicated that 5-HT2 receptor mRNA is present in freshly isolated uterine tissue as well. Selective antagonists of the 5-HT2 receptor, ketanserin and spiperone, displayed concentration-dependent inhibition of serotonin-mediated collagenase induction in the myometrial cultures. These antagonists yielded IC50 values of 4.7 nM and 2.7 nM respectively, characteristic of values expected from a 5-HT2 receptor-mediated response. In addition, a number of selective 5-HT2 receptor agonists (quipazine, alpha-methyl-serotonin, DOI) mimicked the ability of serotonin to induce collagenase production, whereas compounds selective for 5-HT1 and 5-HT3 receptor subtypes had little effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin-dependent collagenase induction in rat myometrial smooth muscle cells: mediation by the 5-HT2 receptor. 847 55