Recently in spite of the interest on the regulation of intracellular Mg^(2+) by neurotransmitters or drugs, the magnesium ion(Mg^(2+)) regulation by α₁-adrenoceptor stimulation has not been studied in the heart yet.
To elucidate the regulation of α₁-adrenoceptor stimulation-induced Mg^(2+) release and the effects of α₁-adrenoceptor stimulation on pathophysiological conditions, in this study we have evaluated the effects of phenylephrine, PMA, H-7. staurosporine, verapamil and lidocaine on Mg^(2+) release in perfused guinea pig heart. During preperfusion exogenous Mg^(2+) was added to the medium to give 1.2mM 15min before starting to addition of drugs, and then the infusion of exogenous Mg^(2+) was stopped. Mg^(2+) in the perfusate leaving the heart was measured by atomic absorption spectrophotometry. Mg^(2+) free solution produced an increase in heart rate and phenylephrine elicited Mg^(2+) release from the heart. Mg^(2+) release by phenylephrine was abolished by combined treatment with prazosin. By contrast, cardiac Mg^(2+) uptake induced by a protein kinase C(PKC) activator, PMA was abolished by a selective PKC inhibitor, staurosporine. And the phenylephrine-induced Mg^(2+) release was not affected by the PKC inhibitor, H_7. When verapamil or lidocaine was added to perfusing solution, Mg^(2+) release was potentiated by phenylephrine from perfused guinea pig heart. These results suggest that α₁-adrenoceptor stimulation caused Mg^(2+) release and that PKC is not involved in α₁-adrenoceptor mediated Mg^(2+) release from perfused guinea pig heart. Under pathophysiological conditions, the Mg^(2+) alteration by α₁-adrenoceptor stimulation is considerable.
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