Effects of histamine H₂-receptor stimulation on Mg²⁺ efflux in perfused guinea pig heart

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), ranitidined (10^-5 M), 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.