Abstract

The neuropeptide substance P (SP) produces transient elevations in short-circuit current (Isc), a measure of active ion transport, across sheets of small intestinal mucosae from several animal species, but the ionic basis of this action remains unknown. The aim of this study was to test the hypothesis that SP promotes electrogenic anion secretion in the porcine proximal jejunum, an intestinal segment analogous to the human upper small intestine. Sheets of jejunal mucosa with attached submucosa responded to serosal (S), but not luminal (L) addition of 0.1 microM SP with a transient increase in Isc that was reduced in tissues pretreated with the Na(+)-K(+)-Cl- cotransport inhibitor bumetanide (10 microM) or bathed in media lacking Cl- or HCO3- ions. SP produced biphasic effects on transepithelial Na+ and Cl- fluxes; it initially stimulated a L-directed Na+ secretory flux during a 5-min period in which peptide-induced Isc elevations were maximum. The return of the Isc to base-line levels was temporally associated with an increase in L-directed Cl- transport. Both effects of SP were absent in tissues either pretreated with the neuronal conduction blocker tetrodotoxin (0.1 microM) or bathed in HCO3(-)-deficient media. Bumetanide abolished the Na+ secretory actions of SP, but did not affect peptide-induced Cl- secretion. pH-Stat titration experiments revealed that mucosal sheets alkalinized the L bathing medium at a rate twice that of the S medium. SP simultaneously increased and suppressed L and S alkalinization, respectively; this effect presumably represents HCO3- secretion.(ABSTRACT TRUNCATED AT 250 WORDS)