The antagonistic effect of cholecystokinin octapeptide (CCK-8) on opioid effects in cardiovascular activities was mediated by CCK-B receptor.
Previous studies have shown that CCK-8 has distinct antiopioid effect in the central sites related with pain control and blood pressure control. The aim of this study was to explore the receptor mechanism by which CCK-8 antagonized the depressor effect of u- and k-opioid agonists, and to observe whether CCK-8 could antagonize the depressor effect induced by muscimol, a nonopioid substance. The results showed that (i) The antagonistic effect of CCK-8 on opioid-induced hypotension could be blocked by intrathecal (i. t.) administration of CCK-B antagonist L-365, 260 at nanogram doses, or by CCK-A antagonist devazepide at doses 20-40 times higher than L-365, 260, indicating that it was the CCK-B receptor which mediates the antiopioid effect. (ii) The depressor effect induced by intrathecal muscimol, a GABA agonist, was blocked neither by naloxone nor by CCK-8, supporting the notion that CCK-8 is an endogenous opioid antagonist rather than a universal anti-hypotension agent.
Mei
L
L
Department of Physiology, Beijing Medical University, PRC.
Han
J S
JS
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D020109:Devazepide; D005260:Female; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy*; D009118:Muscimol; D010671:Phenylurea Compounds; D011377:Proglumide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000502:physiology; D012844:Sincalide / Q000494:pharmacology* / Q000627:therapeutic use
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D009118:Muscimol; C058121:L 365260; D011377:Proglumide; D020109:Devazepide; D012844:Sincalide