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  • Title: Adrenomedullin decreases both cytosolic Ca2+ concentration and Ca(2+)-sensitivity in pig coronary arterial smooth muscle.
    Author: Kureishi Y, Kobayashi S, Nishimura J, Nakano T, Kanaide H.
    Journal: Biochem Biophys Res Commun; 1995 Jul 17; 212(2):572-9. PubMed ID: 7626072.
    Abstract:
    Adrenomedullin (AM) is a newly identified vasorelaxant peptide which circulates in human plasma. We investigated the cellular mechanisms of AM-induced relaxation in the pig coronary artery, using fura-2 fluorometry and receptor-coupled membrane permeabilization by alpha-toxin. AM inhibited both the elevations of cytosolic Ca2+ concentration ([Ca2+]i) and the tension induced by high K(+)-depolarization and by U46619. The extent of the tension inhibition was much greater than expected based on the extent of reductions of [Ca2+]i. Thus, the [Ca2+]i (abscissa)-tension (ordinate) relation shifted to the right by AM. In alpha-toxin-permeabilized strips, AM decreased the tension development at constant [Ca2+]i (pCA 6.5) in the presence of GTP, whereas GDP beta S antagonized this effect. We thus conclude that AM relaxes the coronary artery not only by decreasing [Ca2]i but also by decreasing the Ca(2+)-sensitivity of the contractile apparatus, as mediated by G-protein.
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