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Inhibitory effect of adrenomedullin on L-type calcium currents in guinea-pig ventricular myocytes

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Journal Title:: ACTA PHYSIOLOGICA SINICA

Issue:: Volume 54, Issue 06, 2002

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Key Word:: adrenomedullin;ventricular myocyte;receptor;protein kinase C;L-type calcium channel;patch clamp technique

Abstract： The effects of adrenomedullin (ADM) on the L-type calcium currents (ICa,L) and the mechanism of the signal transduction process were studied. Enzymatically isolated guinea-pig ventricular myocytes were used to measure ICa,L with whole-cell patch-clamp techniques. ADM at the concentrations of 1～100 nmol/L decreased ICa,L in a dose-dependent manner (P<0.05). ADM22-52 (100 nmol/L), a specific ADM-receptor antagonist, completely abolished the ADM-induced inhibition of ICa,L. Pretreatment of the cells with H-89 (10 μmol/L) , a specific PKA inhibitor, did not attenuate the effects of ADM. Intracellular application of 10 μmol/L PKC19-36 , a specific PKC inhibitor, prevented the ADM-induced inhibition of the ICa,L, while the specific PKC activator PMA could mimic the effects of ADM on the ICa,L. PMA (1 μmol/L) decreased the ICa,L by 32.26±4.20% (P<0.05). These findings indicate that ADM can inhibit the ICa,L in guinea-pig ventricular myocytes, and the inhibition is mediated by the specific ADM-receptor and an activation of protein kinase C.

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