Role of protein kinase C in opioid modulation of glycine-gated Cl − current in rat periaqueductal gray neuron

Abstract

The Role of protein kinase C in the modulatory effect of a μ-opioid receptor agonist, [ d-Ala 2, N-Me-Phe 4,Gly 5-ol]enkephalin (DAMGO), on the glycine-gated Cl − current was examined in acutely dissociated rat periaqueductal gray neurons. Using the nystatin-perforated patch-clamp technique, the neurons were voltage-clamped at −60 mV. The glycine-gated Cl − current ( I Gly) was sensitive to strychnine. On pretreatment with 1 μM DAMGO, the 30-μM glycine response increased with time and showed a maximum amplitude of 209±37% of control. After a protein kinase C activator, phorbol-12-myristate-13-acetate (PMA, 0.1 μM) as pretreatment, I Gly increased to 138±6% of control. The DAMGO potentiation of I Gly was not altered by coapplication with PMA. Although protein kinase C inhibitors, chelerythrine (3 μM) and 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) maleimide (GF109203X, 1 μM), did not alter I Gly, the DAMGO-induced potentiation of I Gly was reduced to 161±21% or 164±31% of the control after coapplication with chelerythrine or GF109203X, respectively. These results indicate that the potentiation of I Gly by a μ-opioid receptor agonist is partly mediated by activation of protein kinase C.