Contractions of isolated canine coronary arteries resistant to S2-serotonergic blockade

The purpose of this study was to compare the effect of two serotonergic receptor antagonists on the contractile responses mediated by 5-hydroxytryptamine (5-HT) in isolated canine coronary arteries. After removing the endothelium and blocking neuronal uptake with cocaine, the coronary artery contracted when exposed to nanomolar concentrations of 5-HT; at micromolar concentrations the amine caused relaxation. A relatively high concentration of the selective S2-serotonergic antagonist, ketanserin (10(-6) M), attenuated peak contractions caused by 5-HT by an average of only 52% and caused no significant change in sensitivity to the amine. In contrast, the antagonist behaved competitively in the canine femoral artery. Cyproheptadine (10(-6) M) also was a noncompetitive serotonergic antagonist in the coronary artery. The relatively nonselective S1- and S2-serotonergic receptor antagonist, methiothepin, competitively antagonized coronary contractions caused by 5-HT with an estimated pA2 of 8.0. The rightward shifts of coronary serotonergic contractions caused by methiothepin were not significantly different whether or not ketanserin (10(-6) M) was present in the assay to block S2-serotonergic receptors. Unlike ketanserin, methiothepin (10(-6) M) nearly abolished coronary artery contractions caused by aggregating platelets. These results indicate that serotonergic coronary contractions are resistant to S2-serotonergic blockade, and suggest that they are mediated at least in part by receptors which are different from the S2-serotonergic subtype.