Protein kinase C modulates neurotransmitter responses in Xenopus oocytes injected with rat brain RNA

Oocytes of the frog Xenopus laevis express various exogenous neurotransmitter receptors and ion channels when injected with RNA from excitable tissues. The oocytes serve as a convenient model system in which modulation of neurotransmitter responses can be studied. We examined the effects of activators and an inhibitor of protein kinase C (PKC) on responses to serotonin (5-HT), acetylcholine (ACh), kainate, and gamma-aminobutyric acid (GABA) in oocytes injected with RNA from rat brain. The PKC activators beta-phorbol esters 4 beta-phorbol-12-myristate-13-acetate (PMA) and 4 beta-phorbol-12,13-dibutyrate (PDBu), as well as the synthetic diacylglycerol, 1-oleyl-2-acetylglycerol (OAG), significantly inhibited the responses to 5-HT and ACh (both known to be mediated by mobilization of intracellular Ca2+); the first (transient) phase of these responses was affected stronger than the second, slow phase. PKC activators also reduced the response to GABA. The effect of PDBu on the response to kainate was dual; either inhibition or potentiation were observed at different concentrations of PDBu. The inactive analogue of PMA, the alpha-PMA, was without effect on the responses to 5-HT and GABA. The PKC inhibitor 1,5-isoquinolinesulfonyl-2-methylpiperazine (H7) suppressed the inhibitory effect of PDBu on 5-HT response. Amiloride, a blocker of the Na+/H+ exchange (which is known to be activated by PKC in some tissues), did not suppress the effects of PDBu. We concluded that activation of PKC down-regulates the responses to 5-HT, ACh and GABA, and has a dual effect on response to kainate. Possible mechanisms of these effects are discussed.