The present study aimed to explore modulation of ATP-activated currents (I(ATP)) by met-Enk in rat DRG neurons. I(ATP) was recorded using the whole-cell patch clamp technique. The majority of the neurons examined responded to ATP (90.0 percent;, 45/50) with inward currents. In the 45 ATP sensitive neurons three kinds of responses to application of met-Enk were distinguished: (l) inward currents (29/45), (2) outward currents (9/45), and (3) no effect (7/45). Pretreatment with met-Enk (10(-9)~10(-5) mol/L) suppressed I(ATP) (10(-4) mol/L) in 29 neurons responding to met-Enk with inward currents. The inhibition by met-Enk of I(ATP) could be blocked by naloxone (10(-7) mol/L) in a concentration-dependent manner. Met-Enk of 10(-9), 10(-8), 10(-7), 10(-6) and 10(-5) mol/L suppressed I(ATP) by l3.2+/-5.4 percent; (n=5); 39.2+/-8.6 percent; (n=8), 54.l+/-8.6 percent; (n=8),43.3+/-7.9 percent; (n=7) and 43.l+/-7.9 percent; (n=7) (mean+/-MSE), respectively. A comparison of concentration - response relations of ATP with and without preapplication of met-Enk indicated that after pretreatment with met-Enk (10(-7) mol/L) the curve shifted downward markedly with a decrease of 25 percent; of the maximum value of I(ATP) and unchanged K(d) value. The suppression of I(ATP) by met-Enk was reversed as evidenced by intracellular dialysis of H-9 by using the repatch technique. Taken together, it is suggested that the inhibition by met-Enk of I(ATP) is caused by activation of opiate receptor, which eventually results in phosphorylation of ATP receptor, mediated by modulation of G protein coupling and intracellular signal transduction.