Adrenomedullin decreases both cytosolic Ca2+ concentration and Ca(2+)-sensitivity in pig coronary arterial smooth muscle.
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.
Kureishi
Y
Y
Division of Molecular Cardiology, Faculty of Medicine, Kyushu University, Japan.
Kobayashi
S
S
Nishimura
J
J
Nakano
T
T
Kanaide
H
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D053607:Adrenomedullin; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D010539:Permeability; D011188:Potassium / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013552:Swine; D013873:Thionucleotides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D010738:Type C Phospholipases / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D010455:Peptides; D011450:Prostaglandin Endoperoxides, Synthetic; D013873:Thionucleotides; D014662:Vasoconstrictor Agents; D006153:Guanosine Diphosphate; D053607:Adrenomedullin; D013928:Thromboxane A2; C023427:guanosine 5'-O-(2-thiodiphosphate); D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D006160:Guanosine Triphosphate; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D011188:Potassium; D002118:Calcium