dynorphin-a(1-12) and normorphine

Extraluminal strain gage transducers were sutured along the transverse axis of the duodenum in order to monitor circular muscle contractile activity in the pentobarbital anesthetized dog. Administration by intravenous bolus of a variety of mu- and delta-directed opioid ligands resulted in a dose-dependent increase in duodenal contractile activity. In contrast, all kappa-directed ligands were devoid of stimulatory activity. Naloxone reversed the effects of normorphine and [Met5]enkephalin but was 20 times more effective against normorphine than [Met5]enkephalin. Based on the inactivity of all kappa ligands examined and the differential potency of naloxone against [Met5]enkephalin and normorphine, we suggest that this model may be useful in the classification of opioid ligands as to their receptor selectivity in vivo. Further, these data indicate that the stimulation of duodenal contractile activity is not mediated by enteric kappa receptors.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Dogs; Duodenum; Dynorphins; Electric Stimulation; Enkephalin, Methionine; Female; Gastrointestinal Motility; Male; Morphine; Morphine Derivatives; Naloxone; Peptide Fragments; Phenazocine; Pyrrolidines; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu