PT - JOURNAL ARTICLE AU - C. M. McKune AU - S. W. Watts TI - Characterization of the Serotonin Receptor Mediating Contraction in the Mouse Thoracic Aorta and Signal Pathway Coupling DP - 2001 Apr 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 88--95 VI - 297 IP - 1 4099 - http://jpet.aspetjournals.org/content/297/1/88.short 4100 - http://jpet.aspetjournals.org/content/297/1/88.full SO - J Pharmacol Exp Ther2001 Apr 01; 297 AB - The purpose of this study was to characterize pharmacologically the 5-HT receptor(s) mediating contraction in the mouse aorta and the pathways these receptors are coupled with to mediate contraction. We hypothesized that a 5-HT2A receptor, as in the rat, mediates contraction by activating L-type calcium channels, phospholipase C (PLC), and tyrosine kinase(s). Endothelium-denuded aortic strips were placed in a tissue bath for measurement of isometric contractile force. 5-HT, the 5-HT2A receptor agonist α-methyl-5-HT, and partial 5-HT2A receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (±-DOI) caused the most potent and efficacious contraction. The 5-HT1E/1F receptor agonist BRL 54443 also induced contraction (−log EC50 = 6.52); however, the 5-HT2A receptor antagonist ketanserin antagonized this contraction. Our hypothesis was further supported by the finding that antagonists with affinity for the 5-HT2A receptor, ketanserin, 1-(1-naphthyl)piperazine, spiperone, and LY53857, reduced 5-HT-induced contraction. A correlation of 0.927 was found between literature-derived compound binding affinities for the agonists and antagonists at the 5-HT2A receptor of the rat and the data generated in our experiments (−log EC50 and pKB values). The L-type calcium channel blockers nifedipine and nitrendipine, PLC inhibitor 2-nitro-4-carboxyphenylN,N-diphenylcarbamate, and tyrosine kinase inhibitors genistein and PD 098,059 all shifted and/or reduced maximum contraction to 5-HT. We conclude that contraction to 5-HT in the mouse aorta is mediated primarily by a 5-HT2A receptor and is coupled to L-type calcium channels, PLC, and tyrosine kinases. The American Society for Pharmacology and Experimental Therapeutics