Cholecystokinin-Induced Antinociception is Not Blocked by CCK-A or CCK-B Receptor Antagonists

Abstract

Williams, C. L., G. C. Rosenfeld and T. F. Burks. Cholecystokinin-induced antinociception is not blocked by CCK-A or CCK-B receptor antagonists. Peptides 18(3) 409–414, 1997.—To determine the relative importance of CCK-A, CCK-B, and opioid receptors in mediating the antinociceptive actions of cholecystokinin, we evaluated the actions of selective agonists and antagonists in the mouse hot plate assay. The agonists used were CCK (1–30 nmol ICV), a CCK-A receptor agonist (SNF9019; 0.3–10 nmol ICV), and a CCK-B receptor agonist (SNF9007; 0.3–10 nmol ICV). The antagonists used were the CCK-A receptor antagonist, L364,718 (12.5 nmol ICV), CCK-B receptor antagonist, L365,260 (2.5–25 nmol ICV), and the nonselective opioid receptor antagonist naloxone (1 mg/kg SC). CCK and its receptor-selective analogues, SNF9019 and SNF9007, resulted in antinociception that was blocked by naloxone, but was not antagonized by L364,718 or L365,260. In contrast, in positive control experiments, the inhibitory effects of CCK, SNF9019, and SNF9007 on gastrointestinal propulsion in mice were antagonized by identical ICV doses of L364,718 and L365,260. We conclude that centrally administered CCK produces antinociception in the mouse hot plate assay via opioid receptors, but independent of CCK-A or CCK-B receptors. It is necessary to speculate that other CCK receptors, not antagonized by currently available selective antagonists, may exist.