Effects of histamine H|2-receptor stimulation on Mg2+ efflux in perfused guinea pig heart

ABSTRACT

Mg2+ is an important regulator of many cardiac functions. However, regulation of intracellular Mg2+ activity in the heart is not well characterized. To assess the effect of histamine H2-receptor stimulation on intracellular Mg2+ regulation, changes in extracellular Mg2+ concentration were examined under a variety of conditions in perfused guinea pig hearts. Mg2+ in the cardiac perfusate was measured by atomic absorbance spectrophotometry. The histamine (10(-6) M induced a marked Mg2+ efflux from the heart. The H2-receptor antagonists, cimetidine (10(-5) M), ranitidine (10(-5) ND, but not a H1-receptor antagonist, diphenhydramine (3 X 10(-6) M), completely blocked the histamine-induced Mg2+ efflux. The Mg2+ efflux could also be induced by forskolin (3 X 10(-6) M), 8-Cl-cAMP (2 X 10(-4) M), permeable cAMP analogue, or dimaprit, (10(-5) M). However, the carbachol (10(-5) M) considerably decreased the efflux of Mg2+. In the presence of papaverine (10(-5) M), a phosphodiesterase inhibitor, dimaprit-induced Mg2+ efflux was potentiated. These results suggest that a significant Mg2+ efflux from perfused guinea pig heart by histamine can be induced by the histamine H2-receptor stimulation and it is suggested that cytosolic cAMP may be linked.