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.
Haji
A
A
Department of Pharmacology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan. mp04ah@ms.toyama-mpu.ac.jp
Takeda
R
R
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D003655:Decerebrate State / Q000503:physiopathology*; D003864:Depression, Chemical; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005260:Female; D008297:Male; D009474:Neurons / Q000187:drug effects*; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors; D015656:Respiratory Mechanics / Q000187:drug effects*; D012137:Respiratory System / Q000294:innervation*; D013116:Spinal Cord / Q000166:cytology*
D017473:Receptors, Opioid, kappa; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer