Neural and non-neural activation of electrogenic secretion by 5-hydroxytryptamine in the rat ileum in vitro.
5-hydroxytryptamine (5-HT) stimulates electrogenic Cl- secretion in rat ileum stripped of its outer smooth musculature and myenteric plexus. The myenteric plexus, however, is a site of 5-HT synthesis in the gut, and the plexus mediates electrogenic ion secretion activated by luminal enterotoxin STa and taurocholate. Thus, we investigated the role of the myenteric plexus in 5-HT-induced electrogenic secretion in vitro by measuring short-circuit current (Isc, microamps) with voltage-clamp apparatus as an index of electrogenic Cl-secretion in rat ileum which was either stripped of the myenteric plexus or was left intact. Serosally added 5-HT stimulated electrogenic Cl- secretion in muscle-stripped and intact ileum in a concentration-dependent manner. Pre-treatment of stripped ileum with atropine (1 micron), hexamethonium (100 microns), tetrodotoxin (1.25 microns) and capsaicin (1 micron) for 15 min did not effect the maximum Isc induced by 5-HT which would implicate a direct action on the enterocyte. In intact ilea, however, tetrodotoxin (TTX) and capsaicin reduced significantly the maximum values of Isc stimulated by 5-HT, and the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) caused a significant decrease in the maximum response to 5-HT. These results suggest that electrogenic secretion induced by 5-HT in rat ileum in vitro occurs partly by activation of a non-neural pathway probably involving a direct interaction with the enterocyte, and partly via a nitrinergic-myenteric secretory reflex activated by sensory afferent fibres. These data highlight the danger of characterising intestinal secretory activity from in vitro experiments by using muscle-stripped tissue only.
Rolfe
V E
VE
Department of Biomedical Science, University of Sheffield, UK.
Levin
R J
RJ
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018738:Hexamethonium / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D017136:Ion Transport; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D009197:Myenteric Plexus / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D002712:Chlorides; D012701:Serotonin; D018738:Hexamethonium; D013779:Tetrodotoxin; D001285:Atropine; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester