Kureishi Y, Kobayashi S, Nishimura J, Nakano T, Kanaide H
Division of Molecular Cardiology, Faculty of Medicine, Kyushu University, Japan.
Biochem Biophys Res Commun. 1995 Jul 17;212(2):572-9. doi: 10.1006/bbrc.1995.2008.
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.
肾上腺髓质素（AM）是一种新发现的血管舒张肽，存在于人体血浆中。我们使用fura-2荧光测定法和α-毒素介导的受体偶联膜通透化技术，研究了AM诱导猪冠状动脉舒张的细胞机制。AM既能抑制细胞内Ca2+浓度（[Ca2+]i）的升高，也能抑制高钾（K+）去极化和U46619诱导的张力。张力抑制的程度远大于基于[Ca2+]i降低程度所预期的结果。因此，AM使[Ca2+]i（横坐标）-张力（纵坐标）关系向右移动。在α-毒素通透的血管条中，在存在GTP的情况下，AM在恒定的[Ca2+]i（pCa 6.5）时降低了张力的产生，而GDPβS则拮抗了这种作用。因此，我们得出结论，AM使冠状动脉舒张不仅是通过降低[Ca2+]i，还通过降低收缩装置对Ca2+的敏感性，这是由G蛋白介导的。
