DUAL OPIOID MODULATION OF CHLORIDE WATER SECRETION IN THE GUINEA-PIG COLON IN-VITRO AND THE RAT JEJUNUM IN-VIVO

1 The short-circuit current, which indicates net chloride secretion un der the present experimental condition, was stimulated by PGE1 plus th eophylline in the guinea-pig colonic mucosa in vitro. 2 It was dose-de pendently inhibited by up to 6 5 % at 1 mumol l-1 by the kappa-selecti ve opioid agonist, U69593. The mu-selective opioid agonist, DAGO, was inactive, while the delta-selective opioid agonist DPDPE displayed abo ut 20% inhibition at 1 mumol l-1. Basal secretion was not inhibited by the three agonists to any biologically relevant degree. 3 The mu-sele ctive opioid antagonist, CTOP-NH2 (0.1 mumol 1-1), partially inhibited PGE1 plus theophylline-stimulated net chloride secretion, suggesting that endogenous opioid peptides enhance secretion. The non-selective o pioid antagonist, naloxone, at the high concentration of 100 mumol 1-1 also partially inhibited net chloride secretion and prevented, upon p re-administration, any further effect of CTOP-NH2. This confirms the o pioid nature of the receptor affected by CTOP-NH2 in vitro. 4 The anti secretory effect of CTOP-NH2 has been confirmed in the rat in vivo usi ng jejunal enteropooling upon continuous stimulation by PGE2. A high d ose (1 mg kg-1 s.c.) of naloxone tended to either inhibit the diarrhoe al action of a high dose of PGE2 (79.1 ng min-1 i.a.) or augment the d iarrhoeal action of a lower dose of PGE2 (31.6 ng min-1 i.a.). The con trasting effects of naloxone may be due to endogenous activation of bo th mu and kappa Opioid receptors at high doses of PGE2 but only mu opi oid receptors at low doses. In either case, no further inhibition by C TOP-NH2 was observed after pretreatment with naloxone, proving the opi oid nature of the receptor affected by CTOP-NH2 in vivo.