Control of guinea pig intestinal electrolyte secretion by a delta-opiate receptor.

Abstract

The effects of opioids on transepithelial potential difference and short-circuit current across guinea pig ileum stripped of 1 muscle layer were measured in vitro in Ussing chambers. Opioid peptides such as [D-Ala2, DLeu5]enkephalin and [D-Ala2, DMet5]enkephalin, which are primarily agonists at .delta.-opiate receptors, were able to reduce transepithelial potential difference and short-circuit current at concentrations as low as 1 nM. The narcotic drug etorphine was very potent in reducing short-circuit current, but fentanyl and morphine, which are primarily agonists at .mu.-opiate receptors, were completely ineffective. Ketocyclazocine was relatively ineffective, and .beta.-endorphin had intermediate potency. All opioid effects could be reversed by the opiate antagonist naloxone. Somatostatin reduced short-circuit current, but its effect was not reduced by naloxone. Cl- flux measurements indicated that the effect of etorphine on short-circuit current is associated with an enhancement of active Cl- absorption. The relative effects of opioids in this system suggest that their actions are being mediated by a specific .delta.-opiate receptor. Opioid effects on guinea pig intestinal smooth muscle seem to be primarily mediated by a .mu.-opiate receptor.