Expression of the GABAB receptor in Xenopus oocytes and inhibition of the response by activation of protein kinase C

Abstract

The functional GABA_B receptor was expressed in Xenopus oocytes by injecting mRNA obtained from the cerebellum of the rat. Application of GABA in the presence of bicuculline induced a hyperpolarization under current‐clamp conditions and an outward current under voltage‐clamp conditions. Baclofen mimicked the effect of GABA in the presence of bicuculline, and the effect of baclofen was antagonized by phaclofen. The GABA‐induced outward current was slightly inhibited by treatment with GDP‐β‐S and was completely inhibited by treatment with GTP‐γ‐S. The activation of protein kinase C by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), but not 4α‐phorbol‐12,13‐didecanoate, suppressed the GABA_B receptor‐mediated hyperpolarization, and the effect of TPA was antagonized by sphingosine. Thus, activation of protein kinase C inhibits the expressed GABA_B receptor‐mediated response.