Effects of a kappa-receptor agonist U-50488 on bulbar respiratory neurons and its antagonistic action against the mu receptor-induced respiratory depression in decerebrate cats.

The function of kappa receptor-mechanisms in bulbar respiratory network was investigated in decerebrate cats. Intravenous injection of U-50488 (0.3-3.0 mg/kg) dose-dependently decreased the phrenic nerve discharge and shortened inspiration and expiration. U-50488 caused hyperpolarization, and decreased input resistance and the action potential discharge in respiratory neurons. The effects of U-50488 were antagonized by nor-binaltorphimine. DAMGO (0.3 mg/kg, i.v.) decreased the phrenic discharge and prolonged inspiration and expiration. U-50488 partially reversed the respiratory depression induced by DAMGO. These results suggest that the activation of K receptors by itself depresses the central respiratory activity, while it opposes the mu receptor-mediated respiratory depression.