Desensitization of endogenous angiotensin II receptors in Xenopus oocytes: a role of protein kinase C.
The inward chloride current induced by angiotensin II (AII) in Xenopus oocytes shows strong and homologous desensitization, and was suggested to be mediated by phosphatidylinositol (PI) hydrolysis (Sakuta et al., 1991, Eur. J. Pharmacol. Mol. Pharmacol. 208, 31). As a model of agonist-induced desensitization of receptors coupled with PI hydrolysis, the mechanism of the desensitization of endogenous AII receptors in oocytes was investigated. Incubation of collagenase-treated oocytes with staurosporine significantly augmented the peak amplitude of AII responses, prolonged their duration, and increased the ratio of oocytes responsive to AII. Moreover, staurosporine-pretreatment made oocytes be consistently responsive to every application of AII. These effects of staurosporine were inhibited by incubation of staurosporine-treated oocytes with 12-O-tetradecanoylphorbol 13-acetate (TPA) but not with dibutyryl cAMP. TPA also attenuated AII responses in staurosporine-untreated control oocytes. These results suggest that staurosporine suppresses the desensitization of endogenous AII receptors in oocytes by blocking protein kinase C (PKC), and the desensitization is likely to be due to phosphorylation by PKC of the receptors or the molecules comprising an AII receptor complex.
Sakuta
H
H
Department of Pharmacology, National Defense Medical College, Saitama, Japan.
Sekiguchi
M
M
Okamoto
K
K
Sakai
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D003994:Bucladesine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D006868:Hydrolysis; D003012:Microbial Collagenase / Q000378:metabolism*; D009865:Oocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014982:Xenopus laevis / Q000378:metabolism
D000470:Alkaloids; D010716:Phosphatidylinositols; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D003994:Bucladesine; D011493:Protein Kinase C; D003012:Microbial Collagenase; D019311:Staurosporine; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate