Inhibition of the antianalgesic action of dynorphin A in mice by cholera toxin

Dynorphin A-(1–17) (Dyn A) administered intrathecally (IT) or released spinally in the mouse produces an antianalgesic action. The present experiments indicate that IT administration of cholera toxin inhibited the antianalgesic action of Dyn A. When clonidine was administered intracerebro-ventricularly (ICV) to release spinal Dyn A, IT cholera toxin inhibited the antianalgesis action of Dyn A so that the analgesic component of action of clonidine became evident. Dyn A given IT inhibited the analgesic action of morphine given ICV. Cholera toxin given IT eliminated the antagonistic action of Dyn A. These results, in addition to others, indicate that IT cholera toxin antagonized the action of Dyn A. When the antianalgesic action of Dyn A was attenuated by pretreatment with dynorphin antiserum or by pretreatment that produced desensitization to Dyn A, cholera toxin had no effect. These results suggested that the antianalgesic action of Dyn A is mediated by activation of opioid receptors that are positively coupled to adenylate cyclase through a G s regulatory protein.