Yohimbine and rauwolscine inhibit 5-hydroxytryptamine-induced contraction of large coronary arteries of calf through blockade of 5 HT2 receptors.

5-Hydroxytryptamine (5 HT)-induced contractions were investigated on cocaine-treated strips of bovine large coronary arteries. 1. The alpha 2-adrenoceptor blockers rauwolscine and yohimbine antagonized competitively 5 HT-induced contractions. The estimated equilibrium dissociation constants KB (-log mol/l) were 7.1 for rauwolscine and 7.3 for yohimbine. The affinity of yohimbine for the receptors mediating the response to 5 HT appears to be 10 times higher than for postsynaptic alpha 1-adrenoceptors but 10 times lower than for postsynaptic vascular alpha 2-adrenoceptors. 2. (-)-Noradrenaline and the alpha 2-adrenoceptor-selective agonist B-HT 920 caused maximum contractions amounting to only 20% and 2%, respectively, of the maximum 5 HT effects. Neither 60 mumol/l B-HT 920 nor 1 mumol/l prazosin antagonized the 5 HT effect. 3. Ketanserin was a competitive antagonist (KB = 9.2 (-log mol/l] of the effects of 5 HT. Combinations of rauwolscine or yohimbine with ketanserin antagonized the 5 HT effects as expected from competition of the 4 drugs for a single class of receptor. 4. The evidence is consistent with an interaction of 5 HT, ketanserin, rauwolscine and yohimbine with 5 HT2 receptors. alpha-Adrenoceptors only play a minor role in large coronary arteries and appear not to be involved in the 5 HT-induced contractions. A possible clinical involvement of 5 HT in coronary artery spasm is discussed.