The action of serotonin (5-HT) on alpha 1- and alpha 2-adrenoceptors was investigated on the isolated dog saphenous vein strip. Prazosin (1 X 10(-6) and 1 X 10(-5) M), an alpha 1-adrenoceptor blocker, did not alter 5-HT-induced contractions. However, yohimbine (1 X 10(-6) and 1 X 10(-5) M), an alpha 2-adrenoceptor blocker, shifted the concentration-response curve of 5-HT to the right without any reduction in the maximum response. The pA2 value for yohimbine against 5-HT (7.61 +/- 0.28, mean +/- S.E.M.) is different from the value for yohimbine against clonidine (8.35 +/- 0.08) or M-7 (8.58 +/- 0.07), a substance which stimulates postsynaptic alpha 2-adrenoceptors. Mianserin (1 X 10(-8)-1 X 10(-6) M) and ketanserin (1 X 10(-7)-1 X 10(-5) M) antagonized 5-HT-induced contractions noncompetitively. The results suggest that yohimbine competitively antagonizes 5-HT action by blocking probably 5-HT1 receptors, independently from its alpha 2-adrenoceptor blocking effect.
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