TY - JOUR T1 - Amplification of 5-hydroxytryptamine-induced contractile responses via 5-hydroxytryptamine receptors and alpha-adrenoceptors in dog mesenteric artery and vein. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 779 LP - 784 VL - 268 IS - 2 AU - H Shimamoto AU - Y Shimamoto AU - C Y Kwan AU - E E Daniel Y1 - 1994/02/01 UR - http://jpet.aspetjournals.org/content/268/2/779.abstract N2 - The interactions between 5-hydroxytryptamine (5-HT) and both serotonergic and alpha adrenoceptors were investigated by using isolated dog mesenteric vascular rings mounted in tissue baths for the measurement of isometric contraction. In the mesenteric artery, 5-HT elicited concentration-dependent contractions, producing 46.5% of the KCl maximal response. At low concentrations, the 5-HT-induced contraction was effectively inhibited by 10(-6) M methysergide and by 10(-6) M ketanserin, but was prazosin-resistant. At high 5-HT concentrations, the contractile response was effectively antagonized by 10(-7) M prazosin. The presence in the medium of 20 mM KCl, which increased resting tension less than 10% of the KCl maximal response, markedly enhanced the responses to 5-HT primarily at concentrations lower than 10(-5) M. These amplified responses were methysergide-sensitive, but prazosin- and ketanserin-resistant. In the mesenteric vein, exposure to 5-HT caused an extremely small contraction, producing 5.2 +/- 4.3% of the KCl maximal response. In the presence of 20 mM KCl, which had small contractile effects, 5-HT produced a biphasic concentration-response curve. Methysergide (10(-6) M) and 10(-6) M ketanserin effectively inhibited the responses to low concentrations of 5-HT, and only 10(-7) M rauwolscine effectively blocked the responses to high concentrations of 5-HT. In the dog mesenteric artery, our data suggest that addition of threshold concentrations of KCl enhanced the contractile response to 5-HT through amplification of 5-HT1-like receptor-mediated responses. In the dog mesenteric vein, KCl enhanced 5-HT responses via amplification of both 5-HT2 receptor- and alpha-2 adrenoceptor-mediated responses. ER -