Interactions between cholecystokinin and opioids in the isolated guinea-pig ileum.
1. Although cholecystokinin octapeptide sulphate (CCK-8) activates the opioid system of isolated guinea-pig ileum (GPI) whether it activates the mu- or kappa-system, or both, remains unclear. Neither is it known whether CCK-8 influences the withdrawal responses in GPI preparations briefly exposed to opioid agonists. This study was designed to clarify whether CCK-8 activates mu- or kappa-opioid systems or both; and to investigate its effect on the withdrawal contractures in GPI exposed to mu- or kappa-agonists and on the development of tolerance to the withdrawal response. 2. In GPI exposed to CCK-8, the selective kappa-antagonist nor-binaltorphimine elicited contractile responses that were concentration-related to CCK-8 whereas the selective mu-antagonist cyprodime did not. 3. In GPI preparations briefly exposed to the selective mu-agonist, dermorphin, or the selective kappa-agonist, U-50, 488H, and then challenged with naloxone, CCK-8 strongly enhanced the withdrawal contractures. 4. During repeated opioid agonist/CCK-8/opioid antagonist tests tolerance to opioid-induced withdrawal responses did not develop. 5. These results show that CCK-8 preferentially activates the GPI kappa-opioid system and antagonizes the mechanism(s) that control the expression of acute dependence in the GPI.
Romanelli
L
L
Institute of Pharmacology and Pharmacognosy, University of Rome La Sapienza P.le A. Moro, Italy. romanellil@uniromal.it
Amico
M C
MC
Mattioli
F
F
Morrone
L A
LA
Valeri
P
P
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009019:Morphinans / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D018847:Opioid Peptides; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000502:physiology; D011957:Receptors, Opioid / Q000187:drug effects*; D012844:Sincalide / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000209:etiology
D009019:Morphinans; D009842:Oligopeptides; D018847:Opioid Peptides; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D011957:Receptors, Opioid; C058450:cyprodime; C030058:dermorphin; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D012844:Sincalide