Nonlinear relationship between α_1 -adrenergic receptor occupancy and phosphatidyl inositol hydrolysys in isolated rat cardiomyocytes

• Published in: Japanese Journal of Pharmacology 1988, Vol.46 (suppl), p.199-199
• Main Authors: Katsuomi Iwakura, Yasuhiro Watanabe, Toshihumi Kagiya, Masatsugu Hori, Takenobu Kamada, Hiroshi Yoshida
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

We investigated the relation between the α_1 -adrenergic receptors occupancy by agonist and subcellular response induced by α_1 -adrenergic stimulation in the cardiomyocytes. The receptor occupancy by agonist was calculated from the inhibition constant, Ki, which were determined from the inhibition curve of norepinephrine (10^-8 -10^-3 M) to the binding of the α_1 -adrenergic specific radioligand,「^^3 H」prazosin, to the α_1 -adrenergic receptors on the isolated rat cardiomyocytes. In another experiments, the cardiomyocytes prelabeled with 「^^3 H」myo-inositol were exposed to the various concentration of norepinephrine (10^-8 -10^-3 M) and the accumulation of 「^^3 H」inositol phosphate was measured as the index of the subcellular response to α_1 -adrenergic stimulation. From these results, we determined the relation between receptor occupancy and PI response. The relation between receptor occupancy and 「^^3 H」inositol phosphate accumulation was non-linear fashion, and the maximum response was induced even when 90%. of α_1 -receptor was occupied by norepinephrine.