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.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D003533:Cyproheptadine / Q000494:pharmacology; D003988:Dibenzothiepins / Q000494:pharmacology*; D015237:Dinoprost; D004285:Dogs; D004351:Drug Resistance; D004727:Endothelium / Q000502:physiology; D005263:Femoral Artery / Q000187:drug effects; D066298:In Vitro Techniques; D007650:Ketanserin; D008719:Methiothepin / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D003988:Dibenzothiepins; D010880:Piperidines; D011460:Prostaglandins F; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D000804:Angiotensin II; D003533:Cyproheptadine; D012701:Serotonin; D008719:Methiothepin; D007650:Ketanserin; D015237:Dinoprost; D003042:Cocaine; D011188:Potassium