Interactions between cholecystokinin and opioids in the isolated guinea-pig ileum

Abstract

1. Although cholecystokinin octapeptide sulphate (CCK-8) activates the opioid system of isolated guinea-pig ileum (GPI) whether it activates the μ- or κ-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 μ- or κ-opioid systems or both; and to investigate its effect on the withdrawal contractures in GPI exposed to μ- or κ-agonists and on the development of tolerance to the withdrawal response. 2. In GPI exposed to CCK-8, the selective κ-antagonist nor-binaltorphimine elicited contractile responses that were concentration-related to CCK-8 whereas the selective μ-antagonist cyprodime did not. 3. In GPI preparations briefly exposed to the selective μ-agonist, dermorphin, or the selective κ-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 κ-opioid system and antagonizes the mechanism(s) that control the expression of acute dependence in the GPI.