Pharmacological characterization of neural mechanisms regulating mucosal ion transport in mouse jejunum

R. J. Sheldon, M. E. Malarchik, D. A. Fox, T. F. Burks, F. Porreca

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Neural regulation of electrolyte transport in mouse jejunum was investigated in vitro using: 1) a full-thickness intestinal segment (intact preparation) and 2) a mucosal preparation, consisting of only mucosa, basement membrane and muscularis mucosa. In Ussing chambers, intact tissues exhibited high- and low-frequency oscillations of basal transmural potential difference (PD) and short-circuit current (I(sc)), whereas mucosal tissues exhibited only low-frequency oscillation of these parameters. High-frequency oscillations of PD and L(sc) were found to originate from muscle activity. Under basal conditions, intact tissues exhibited net Na+ absorption and net Cl- secretion, whereas mucosal tissues displayed greater net Na+ absorption and net Cl- absorption. When applied to the serosal medium of intact tissues, tetrodoxin, a neurotoxin, and chlorisondamine, a ganglionic blocking agent, caused a concentration-dependent reduction of basal PD and I(sc), whereas atropine produced no significant effect; these agents were without effect in mucosal tissues. Furthermore, in intact tissues, tetrodotoxin caused significant increases in net Na+ absorption and net residual flux, attaining values that were comparable to those seen in mucosal tissues. Carbachol, a muscarinic agonist, and 1,1-dimethyl-4-phenylpiperizinium, a ganglionic stimulant, elicited concentration-dependent, transient increases of basal PD and I(sc) when applied to the serosal medium of intact tissues; in mucosal preparations, carbachol elicited greater changes of basal PD and I(sc), whereas 1,1-dimethyl-4-phenylpiperizinium produced no significant effect. In intact tissues, I(sc) responses elicited by carbachol were antagonized by atropine, but not tetrodoxin or chlorisondamine; I(sc) responses induced by 1,1-dimethyl-4-phenylpiperizinium, however, were blocked by tetrodoxin or chlorisondamine, but not atropine. These results support the existence of a multisynaptic, and tonically active neural pathway which serves to limit intestinal Na+ transport at some point below the maximal absorptive capacity of the mucosa. Furthermore, cholinergic muscarinic and nicotinic receptors are present in distinct neural pathways that influence intestinal electrolyte transport in the small intestine of the mouse.

Original languageEnglish (US)
Pages (from-to)572-582
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume249
Issue number2
StatePublished - 1989

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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