Effects of Histamine $H_2-Receptor$ Stimulation on $Mg^{2+}$ Efflux in Perfused Guinea Pig Heart

$Mg^{2+}$ is an important regulator of many cardiac functions. However, regulation of intracellular $Mg^{2+}$ activity in the heart is not well characterized. To assess the effect of histamine $H_2$-receptor stimulation on intracellular $Mg^{2+}$ regulation, changes in extracellular $Mg^{2+}$ concentration were examined under a variety of conditions in perfused guinea pig hearts. $Mg^{2+}$ in the cardiac perfusate was measured by atomic absorbance spectrophotometry. The histamine ($10^{-6}$ M) inuced a marked $Mg^{2+}$ efflux from the heart. The $H_2$-receptor antagonists, cimetidine ($10^{-6}$ M), ranitidined ($10^{-5}$ M), but not a H1-receptor antagonist, diphenhydramine ($3{\times}10^{-6}$ M), completely blocked the histamine-induced $Mg^{2+}$ efflux. The $Mg^{2+}$ efflux could also be induced by forskolin ($3{\times}10^{-6}$ M), 8-Cl-cAMP ($2{\times}10^{-4}$ M), permeable cAMP analogue, or dimaprit, ($10^{-5}$ M). However, the carbachol ($10^{-5}$ M) considerably decreased the efflux of $Mg^{2+}$. In the presence of papaverine ($10^{-5}$ M), a phosphodiesterase inhibitor, dimaprit-induced $Mg^{2+}$ efflux was potentiated. These results suggest that a significant $Mg^{2+}$ efflux from perfused guinea pig heart by histamine can be induced by the histamine $H_2$-receptor stimulation and it is suggested that cytosolic cAMP may be linked.