Protein kinase C activity alters the effect of μ-opioid receptors on inhibitory postsynaptic current in the striosomes

We have previously reported that earlier blockade of protein kinase C (PKC) augments the suppressive effect of l-opioid receptors (MORs) on the GABAergic inhibitory postsynaptic current (IPSC) in the MOR-rich striosomes of the striatum. Interestingly, striatal medium-spiny neurons have muscarinic acetylcholine receptor subtypes M-1 and M-4, among which M-1 activates the phosphoinositide signaling pathway yielding PKC. In this study, we examined whether acetylcholine regulates the effects of MOR on presynaptic IPSC by binding to the M-1 receptor, and found that IPSC suppression by the MOR agonist, [D-Ala(2)-N-Me-Phe(4), Gly(5)-ol]-enkephalin, was significantly augmented and prolonged by the PKC inhibitor chelerythrine and attenuated by the PKC activator, phorbol 12, 13-dibutyrate. This modulatory action by chelerythrine was mimicked by the muscarinic antagonist atropine and the M-1-specific antagonist pirenzepine, whereas M-2-M-4 antagonists had no discernible effect. These results suggest that PKC activity modulates the effect of MOR by muscarinic receptors in the striosomes. NeuroReport 23: 184-188 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.