Several recent studies demonstrate that receptor-mediated cAMP (adenosine 3´,5´-monophosphate) production evokes marked change in magnesium (Mg^(2+)) homeostasis. The effects of dimaprit or/and phosphodiesterase (PDE) inhibitors on the Mg^(2+) release from perfused guinea pig heart and collagenase-dispersed myocytes was studied to clarify an association of H₂-histaminergic receptor-mediated Mg^(2+) regulation with intracellular cAMP-degradation system.
Mg^(2+) efflux was stimulated in perfused hearts and myocytes by IBMX (3-isobutyl-1-methylxanthine), a calmodulin-sensitive PDE inhibitor, but not by RO 20-1724(4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone) or papaverine, cAMP-specific PDE inhibitors. Mg^(2+) efflux was also be induced by dimaprit, a H-2-agonist. Mg^(2+) effluxes induced by dimaprit were augmented by the presence of the PDE inhibitors. The augmentation of dimaprit-induced Mg^(2+) effluxes by the PDE inhibitors were inhibited by ranitidine, a H₂-antagonist, and imipramine, a Na^+-Mg^(2+) exchange inhibitor, in perfused hearts and myocytes and were also inhibited by amiloride in perfused hearts. These results suggest that the H₂-stimulated Mg^(2+) effluxes from guinea pig heart can be regulated by the cytosolic nonspecific-dependent PDE systems and that it is induced by the Na^+-Mg^(2+) exchanger stimulation.
|