Desensitization by cyclic AMP-dependent protein kinase of GABAB receptor expressed in Xenopus oocytes.
Involvement of cyclic AMP-dependent protein kinase in the desensitization of GABAB receptor expressed in Xenopus oocytes was studied. GABA produced an outward current in the presence of bicuculline, under voltage-clamp conditions. Baclofen mimicked the effect of GABA, thereby indicating that the response to GABA in the presence of bicuculline is mediated by stimulation of GABAB receptor. The GABAB receptor-mediated response was suppressed by dibutyric cyclic AMP and forskolin, but not by 1,9-dideoxy-forskolin, and the effect of dibutyric cyclic AMP was inhibited by H-8. Application of GABA for 1 min at 20-min intervals induced a reliable response, while that at 10-min intervals produced a desensitization. The desensitization was also partially prevented by H-8. Dibutyric cyclic GMP, 8-bromo-cyclic GMP and Na-nitroprusside did not affect the GABAB receptor-mediated response. Thus, cyclic AMP-dependent protein kinase, but not cyclic GMP-dependent protein kinase participates in desensitization of the GABAB receptor expressed in Xenopus oocytes.
Yoshimura
M
M
Department of Pharmacology, Nagasaki University School of Medicine, Japan.
Yoshida
S
S
Taniyama
K
K
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002531:Cerebellum; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D015870:Gene Expression; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018755:GABA Agonists; D018756:GABA Antagonists; D007546:Isoquinolines; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D012313:RNA; D003994:Bucladesine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D017868:Cyclic AMP-Dependent Protein Kinases; D001418:Baclofen; D001640:Bicuculline