Different and common intracellular calcium-stores mobilized by noradrenaline and caffeine in vascular smooth muscle.

Abstract

Noradrenaline (NA) 1 microM and caffeine (CAF) 10 mM induce a contractile response in isolated rat aorta maintained at 37 degrees C either in the presence or absence of extracellular calcium. In Ca-free media the contractile response was reduced and contractile activity of CAF only occurred at 25 degrees C. NA induced a biphasic response in Ca-free medium, with a fast phasic contraction followed by a smaller more sustained contraction. The response induced by CAF consisted of a fast transient contraction which returned to a level below the resting tone. After washing, further addition of NA or CAF evoked no increase in smooth muscle tension. The influence of Mg-depletion in the extracellular medium on the contractile responses induced by NA and CAF in Ca-free medium was determined: similar response to NA or CAF in media with or without Mg after 2 min loading were observed, but after 15 min loading in Mg, Ca-free solution, the responses to NA or CAF were significantly higher than after incubation in Ca-free medium containing Mg. Differences were observed when contractile response to NA was elicited after the refilling process by loading the aortic strip in Ca-containing Mg-free solution. In this case, instead of recovering the magnitude of contraction there was a significant decrease. The existence of two independent intracellular Ca-pools releasable by NA, one of them also sensitive to CAF, is postulated. The refill of the Ca-store specific to NA is dependent on the presence of Mg in the extracellular medium. In contrast, the refill of the common Ca-pool releasable by NA and CAF is independent of the extracellular Mg, but its spontaneous emptying is temperature-, and Mg-dependent. This suggests the intermediacy of an enzymatic process to extrude the Ca-content of this store to the extracellular space.