Mechanisms of the contractile effect induced by uridine 5-triphosphate in canine cerebral arteries.
This study was performed to elucidate mechanisms responsible for the contraction of isolated canine cerebral arteries induced by uridine 5'-triphosphate (UTP) and to ascertain whether UTP given intracisternally causes cerebral arterial constriction. The latter was proven arteriographically to be the case. In vitro, UTP (10(-4)M) and UDP were similar in potency, produced sustained contractions, and were more effective than other pyrimidine nucleotides or uridine. Unlike serotonin (5-HT), UTP was not antagonized by cinanserin and failed to cause constriction of mesenteric arteries. Adenosine similarly antagonized 5-HT and UTP. The Ca2+ antagonist nimodipine abolished contractions caused by high K+ but only incompletely antagonized 5-HT or UTP. On the other hand, procedures that hyperpolarize the cell membrane (low K+ followed by K+) abolished tonic contractions induced by UTP. Hyperpolarization prior to UTP (with or without nimodipine) did not, however, prevent the occurrence of a phasic contraction. Papaverine or lanthanum antagonized this phasic response. It was concluded that UTP selectively affects cerebral arteries, may initiate contraction by releasing membrane bound Ca2+, depolarizes the cell membrane to open receptor operated and potential sensitive calcium channels, but does not inhibit the electrogenic Na-pump nor specifically antagonize the vasodilator adenosine.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002539:Cerebral Arterial Diseases / Q000139:chemically induced; D002536:Cerebral Arteries / Q000187:drug effects*; D002946:Cisterna Magna; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007267:Injections; D008297:Male; D011742:Pyrimidine Nucleotides / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013035:Spasm / Q000139:chemically induced; D013997:Time Factors; D014500:Uracil Nucleotides / Q000494:pharmacology*; D014544:Uridine Triphosphate / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D011742:Pyrimidine Nucleotides; D014500:Uracil Nucleotides; D012701:Serotonin; D014544:Uridine Triphosphate