Autoradiographic localization of kappa opiate receptors to deep layers of the cerebral cortex may explain unique sedative and analgesic effects.
The pharmacologically defined kappa drug 3H-ethylketazocine (3H-EKC) and 3H-bremazocine bind to unique sites, but also to mu and delta receptors. By displacing mu and delta interactions with morphine and D-Ala2, D-Leu5-enkephalin (DADL) respectively we have visualized selective receptors for 3H-EKC and 3H-bremazocine. These two kappa ligands are localized to sites different from mu and delta receptors labeled with 3H-dihydromorphine (3H-DHM) and 3H-DADL. The highest density and most selective localization of putative kappa receptors occurs in layers V and VI of the cerebral cortex. Cells in these layers project to the thalamus, regulating sensory input to the cortex. These deep cortical kappa receptors may account for the unique sedative and analgesic actions of kappa opiates.
D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects*; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D016314:Ethylketocyclazocine; D006168:Guinea Pigs; D011957:Receptors, Opioid / Q000302:isolation & purification*; D017473:Receptors, Opioid, kappa; D014316:Tritium
D000700:Analgesics; D000701:Analgesics, Opioid; D001575:Benzomorphans; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D014316:Tritium; D016314:Ethylketocyclazocine; C027248:bremazocine; D003496:Cyclazocine