AJP - Heart and Circulatory Physiology, Vol 246, Issue 2 306-H311, Copyright © 1984 by American Physiological Society
cAMP-dependent reduction in membrane fluxes during relaxation of arterial smooth muscle
A. W. Jones, D. B. Bylund and L. R. Forte
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.
