OPIOID RECEPTORS ON GUINEA-PIG INTESTINAL CRYPT EPITHELIAL-CELLS

1. Opioid peptides promote net intestinal absorption via two mechanism s: stimulation of Na+ and Cl- absorption and inhibition of Cl- secreti on. Although these transport changes are predominantly mediated by sub mucosal neurones, it is currently unclear whether opioid peptides can regulate enterocyte function directly. We therefore tested the hypothe sis that enterocytes have specific opioid receptors. 2. Villus and cry pt jejunal epithelial cells were isolated by the distended sac method from anaesthetized guinea-pigs. Flow cytometry mras used to resolve en terocytes from other cell types and to determine whether binding of a fluorescently labelled opioid antagonist, naltrexone-FITC, could be pr evented by unlabelled mu- and delta-opioid receptor agonists. A popula tion of crypt enterocytes (similar to 21%) exhibited high-affinity nal trexone-FITC binding to both mu- and delta-type binding sites that was stereoselective and sodium dependent. Villus enterocytes did not exhi bit any of these characteristics. 3. Basal cAMP production was elevate d ill both villus and crypt cells treated with IBMX (3-isobutyl-1-meth ylxanthine). Villus cells did not respond to 100 nM vasoactive intesti nal peptide (VIP), nor mere they affected by opioid peptides. In contr ast, 100 nM VIP significantly increased cAMP production in crypt epith elial cells, which was significantly reduced by both morphiceptin and D-Ser(2)-Leu-Enk-Thr. This opioid-mediated effect was stereoselective and blocked by the opioid receptor antagonist naltrexone. 4. These exp eriments suggest that enterocytes isolated from the crypt epithelium o f guineapigs have both mu- and delta-types of opioid receptors. It is possible that these cells participate in opioid-mediated regulation of intestinal secretion.