Cellular mechanisms of opiate receptor stimulation in cat middle cerebral artery.

To determine some of the cellular mechanisms of opiate receptor stimulation in cat middle cerebral arterial muscle, intracellular electrical measurements and force development were monitored before and after addition of morphine. Addition of morphine resulted in a dose-dependent hyperpolarization of the muscle cells in the middle cerebral artery with a concomitant relaxation, indicating a high degree of electromechanical coupling in this preparation. The curve relating membrane potential vs. morphine was shifted to the right and downward by naloxone, demonstrating competitive inhibition at receptor sites. When middle cerebral arteries were studied from animals which had been injected with morphine prior to sacrifice, a significant hyperpolarization of the membrane was recorded when studied in an organ bath. This hyperpolarization was abolished if the animal had been pretreated with naloxone prior to morphine injection, suggesting that morphine may act in vivo as we have observed it to act in vitro. Morphine-induced hyperpolarization could be blocked in the organ bath when potassium conductance (gk) was inhibited. Similarly, the reduction in the slope of the voltage/current curve induced by morphine was blocked by agents which reduced gk. These data suggest the presence of opiate receptors on cat cerebral artery and suggest that morphine relaxes these vessels through a mechanism involving increased gk. These findings suggest a role for opiate-mediated systems in cerebral vascular control.