title: cAMP-dependent reduction in membrane fluxes during relaxation of arterial smooth muscle.
abstract: Forskolin, an activator of adenylate cyclase, inhibited contractures induced in rat aorta by norepinephrine (NE) and angiotensin II and by KCl depolarization. The concentration of forskolin required to inhibit NE-induced contractures was significantly lower than required to inhibit KCl-induced contractures (IC50 0.18 +/- 0.01 vs. 2.2 +/- 0.2 microM). Forskolin effectively relaxed NE-induced contractures when active Na+-K+ transport was inhibited. Stimulation of 42K and 36Cl effluxes by NE was inhibited by low concentrations of forskolin. The IC50 for forskolin inhibition of 42K efflux, 0.17 +/- 0.02 M, was similar to that for relaxation of NE contraction. The time course for forskolin-induced increases in adenosine 3',5'-cyclic monophosphate (cAMP) was consistent with that for forskolin-mediated relaxation and its maintenance. Fifty percent inhibition of both NE-induced contractures and NE-stimulated 42K effluxes occurred at levels of cAMP that were 1.4 times basal, and 90% inhibition of both processes was associated with a two to threefold increase in cAMP content. In sharp contrast, the level of tissue cAMP associated with inhibition of KCl contractures was 6-10 times higher than that associated with inhibition of NE-induced contractures. We postulate that cAMP-dependent regulation of membrane fluxes stimulated by receptor occupancy represents a primary mechanism for relaxation of a NE contracture, whereas the processes that regulate depolarization-dependent channels and the phosphorylation of myosin light chain kinase occur at much higher cAMP content and apparently function in a secondary capacity.
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000502:physiology*; D005576:Colforsin; D000242:Cyclic AMP / Q000502:physiology*; D004224:Diterpenes / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011197:Potassium Radioisotopes / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D004224:Diterpenes; D011197:Potassium Radioisotopes; D000804:Angiotensin II; D005576:Colforsin; D000242:Cyclic AMP; D009638:Norepinephrine