Pharmacological characterization of neural mechanisms regulating mucosal ion transport in mouse jejunum.
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 (Isc), whereas mucosal tissues exhibited only low-frequency oscillation of these parameters. High-frequency oscillations of PD and Isc 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, tetrodotoxin, a neurotoxin, and chlorisondamine, a ganglionic blocking agent, caused a concentration-dependent reduction of basal PD and Isc, 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 Isc when applied to the serosal medium of intact tissues; in mucosal preparations, carbachol elicited greater changes of basal PD and Isc, whereas 1,1-dimethyl-4-phenylpiperizinium produced no significant effect. In intact tissues, Isc responses elicited by carbachol were antagonized by atropine, but not tetrodotoxin or chlorisondamine; Isc responses induced by 1,1-dimethyl-4-phenylpiperizinium, however, were blocked by tetrodotoxin 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Sheldon
R J
RJ
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson.
Malarchik
M E
ME
Fox
D A
DA
Burks
T F
TF
Porreca
F
F
D000200:Action Potentials; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001692:Biological Transport; D002217:Carbachol / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004573:Electrolytes / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D009197:Myenteric Plexus / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D004573:Electrolytes; D013779:Tetrodotoxin; D004246:Dimethylphenylpiperazinium Iodide; D001285:Atropine; D002217:Carbachol; D013806:Theophylline; D009543:Nifedipine