The role of adenylate cyclase in relaxation of brain arteries: studies with forskolin.
The natural product, forskolin, which stimulates adenylate cyclase by a direct, non-receptor-mediated mechanism, was studied for its effect on the tension of isolated brain arteries and adenylate cyclase activity of cerebral arteries. Helical strips of bovine and porcine basilar arteries and bovine middle cerebral arteries, which had been precontracted with prostaglandin F2 alpha (PGF2 alpha) or KCl, relaxed potently to administration of forskolin with ED50 values, ranging from 22 to 69 nM. Incubation of forskolin with a broken cell preparation of bovine cerebral arteries resulted in an efficacious stimulation of adenylate cyclase, approximating 5 times basal activity at a forskolin concentration of 1 microM. The metal salts nickel chloride and manganese chloride decreased the potency of vasorelaxation by vasoactive intestinal peptide (VIP), which stimulates adenylate cyclase via the VIP receptor. In contrast, nickel chloride had little effect on vasorelaxation by forskolin. The endogenous nucleoside, adenosine, which acts via the adenosine receptor and adenylate cyclase, relaxed bovine basilar and middle cerebral arteries with ED50 values ranging from 0.26 to 0.94 microM. The data presented support a role for adenylate cyclase in mediating vasodilation of brain blood vessels.
Suzuki
Y
Y
Department of Pharmacology, University of Calgary, Alta., Canada.
Huang
M
M
Lederis
K
K
Rorstad
O P
OP
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry; D002417:Cattle; D002536:Cerebral Arteries / Q000187:drug effects* / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D013552:Swine
D005576:Colforsin; D000262:Adenylyl Cyclases