Neurohormonal regulation of ion transport in the porcine distal jejunum. Enhancement of sodium and chloride absorption by submucosal opiate receptors

Abstract

The actions of opiates in modulating ion transport across the porcine distal jejunal mucosa were examined in vitro. Opiate receptors were functionally characterized using [D-Pen2,D-Pen5]-enkephalin (DPDPE), [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and U-50,488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]-benzeneacetamide), agonists selective for delta, mu and kappa receptor types, respectively. Serosal administration of opiate agonists produced concentration-dependent decreases in basal short-circuit current (Isc. DPDPE and DAMGO also increased tissue conductance (Gt). DPDPE (EC50 = 4 nM) was 7- and 86-fold more potent in decreasing basal Isc than DAMGO and U-50,488, respectively. U-50,488 displayed the greatest efficacy in decreasing Isc. Serosal naloxone decreased DPDPE and DAMGO potencies under basal conditions with Ke values of 11 and 6 nM, respectively. DPDPE- and DAMGO-induced decreases in basal Isc were associated with increases in net Cl absorption; in addition, DAMGO produced an increase in net Na absorption. 8-Bromocyclic AMP (0.3 mM) increased Isc, decreased Gt and inhibited net Na and Cl absorptive fluxes. Selective opiate agonists decreased cyclic AMP-induced elevations in Isc with a rank order of potency (DPDPE, EC50 = 3 nM) of DPDPE greater than DAMGO greater than U-50,488. DPDPE reversed the action of cyclic AMP on Isc and Cl absorption but had no effect on net Na transport. Cyclic AMP-induced decreases in Gt were not altered by DPDPE.(ABSTRACT TRUNCATED AT 250 WORDS)