Magnesium (Mg^(2+)) transport across the plasma membrane of cardiac myocytes appears to be under hormonal control. Repeated stimulations with adrenergic or histaminergic agonist produced a progressive decrease in Mg^(2+) efflux from hearts. Thus we hypothesized that the Mg^(2+) efflux may be resulted from a down-regulation of receptors or from a depletion of Mg^(2+) from intracellular pool(s) in the hearts. In the present study, the regulation of Mg^(2+) homeostasis by receptor stimulation was studied in perfused rat and guinea pig hearts.
The successive short addition of norepinephrine (NE) to rat and guinea pig, and of histamine (HT) to perfused guinea pig hearts induced a progressive decrease in Mg^(2+) efflux. These Mg^(2+) effluxes were blocked by propranolol or ranitidine, respectively. These decrease in Mg^(2+) efflux were inhibited by sodium cyanide (NaCN), which increases intracellular Mg^(2+) ([Mg^(2+)]_i) levels. When NE (or HT) was added after HT (or NE), this efflux was also decreased in the guinea pig hearts. In the rat hearts and myocytes, HT did not stimulate Mg^(2+) efflux. But NE produced a large Mg^(2+) efflux after stimulation with HT. 8-(4-Chlorophenylthio)-adenosine cAMP (cAMP), like NE and HT, also induced a progressive decrease in Mg^(2+) efflux in guinea pig hearts. This effect was inhibited by NaCN. These data provide evidence that the progressive decrease in receptor-stimulated Mg^(2+) efflux is considered to be due to a decrease in [Mg^(2+)]_i levels rather than receptor down-regulation.
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