AJP - Cell Physiology, Vol 257, Issue 3 C413-C418, Copyright © 1989 by American Physiological Society
Forskolin and caffeine induce Ca2+ release from intracellular stores in rabbit aorta
C. M. Hai and R. D. Phair
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
We combined techniques of 45Ca efflux and computer-assisted kinetic
analysis to investigate the effects of forskolin and caffeine on
intracellular Ca2+ metabolism in intact rabbit aortic segments. When either
1 microM forskolin or 10 mM caffeine was present during the 45Ca load and
efflux, the amount of 45Ca released from the tissue was reduced during the
interval between 50 and 250 min of efflux. In contrast caffeine but not
forskolin induced an acute increase in 45Ca efflux when added to the
perfusion medium after 1 h of efflux in physiological salt solution.
Preincubation with caffeine abolished phenylephrine-stimulated 45Ca
release, but preincubation with forskolin had no effect. Kinetic analysis
of these data indicated that caffeine reduced the Ca2+ content of the same
intracellular compartment depleted by phenylephrine, whereas forskolin
depleted a different intracellular Ca2+ store. Forskolin-induced depletion
of an intracellular Ca2+ store was surprising in light of current evidence
suggesting adenosine 3',5'-cyclic monophosphate stimulation of sarcoplasmic
reticular Ca2+ uptake, but hypotheses that included only this mechanism are
inconsistent with our findings.
