Mobilization of a common source of smooth muscle Ca2+ by norepinephrine and methylxanthines

Abstract

The ability of norepinephrine (NE), caffeine (CAF), theophylline (THEO), dinitrophenol (DNP), and potassium (high K) to mobilize cellular Ca2+ in rabbit aorta was examined using 45Ca-efflux techniques. After 10 min of Ca2+ deprivation using either Ca-free EGTA or Ca-free lanthanum (La3+) buffers, NE, CAF, and DNP still caused an increase in 45Ca-efflux rate, indicating a cellular source of 45Ca, while high K did not. Contractile behavior after Ca removal paralleled 45Ca-efflux events. CAF (10 mM) inhibited NE contractile responses, and this inhibition was associated with the depletion of the NE-releasable Ca2+ store. Previous exposure to CAF during 45Ca efflux reduced subsequent stimulation of 45Ca efflux was not additive. THEO caused a stimulation of 45Ca efflux similar to CAF. CAF, THEO, and 3-isobutyl-l-methylxanthine caused a two- to threefold increase in cAMP levels in association with their stimulation of 45Ca efflux. These results suggest that NE and methylxanthines mobilize a common cellular Ca2+ source that is associated with contraction in the case of NE but relaxation in the case of methylxanthines.