Characterization of the opiate receptor population mediating inhibition of VIP-induced secretion from the small intestine of the rat

Abstract

Net water transport was measured from the jejunum of anaesthetized rats by a re-circulation technique. Several narcotic analgesics were administered intravenously and assessed for activity in reversing net fluid secretion induced by intra-arterial infusion of vasoactive intestinal peptide (VIP). The mu-opiate agonists, morphine, RX 783006 and FK 33-824 produced full reversal of the secretory phase of the VIP response, but failed to restore totally fluid transport to the control level of net absorption. The kappa-agonist, ethylketocyclazocine, caused only partial reversal of VIP-induced secretion while the more selective kappa-agonist, MR 2034, produced a small though non-significant antisecretory effect at high doses. The delta-agonist, D-Ala2-D-Leu5-enkephalin also had negligible antisecretory activity. Naloxone caused a parallel displacement to the right of the antisecretory dose-response line to morphine. The 'in vivo pA2' value of naloxone was 7.14. The results are compared with previously published antinociceptive activities of the opiate agonists and in vivo pA2 values of naloxone. It is concluded that stimulation of mu-opiate receptors mediates inhibition of VIP-induced fluid secretion from the rat jejunal mucosa.