Browsing by Author "Levin, Roy J."

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    Enterotoxin Escherichia coli STa activates a nitric oxide-dependent myenteric plexus secretory reflex in the rat ileum.
    (Journal of Physiology, 1994) Rolfe, Vivien E.; Levin, Roy J.
    Mucosally added enterotoxin Escherichia coli STa increased the electrogenic Cl- secretion measured as the short-circuit current (Isc) across isolated muscle-stripped and muscle-unstripped rat mid-ilea incubated in vitro. 2. Pretreatment with serosal L-NAME (N omega-nitro-L-arginine methyl ester) or tetrodotoxin (TTX) significantly reduced the maximum Isc and the duration of action of STa in the unstripped but not stripped ilea. D-NAME (serosal), indomethacin or 5-hydroxy-tryptamine-desensitization was ineffective on STa-induced Isc in either stripped or unstripped ilea. 3. Serosal capsaicin reduced the maximum Isc of STa and its duration of action in unstripped ilea. 4. L-Arginine induced a significantly larger increase in the Isc across unstripped ilea than across stripped ilea; this could be significantly reduced by serosal L-NAME or TTX, although these were ineffective in stripped ilea. 5. Pretreatment of anaesthetized rats with I.P. L-NAME suppressed the fluid secretion induced by luminal STa in ilea in vivo but had no effect on that induced by luminal carbachol. 6. Mucosal STa increased electrogenic Cl- secretion across intact rat ileum in vitro by activating a capsaicin-sensitive, nitric oxide-dependent myenteric plexus-mediated secretory reflex. The suppression by L-NAME of STa induced ileal fluid secretion in vivo probably involves the inhibition of this reflex.
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    Neural and non-neural activation of electrogenic secretion by 5-hydroxytryptamine in the rat ileum in vitro.
    (Acta Physiologica Scandinavica., 1998) Rolfe, Vivien E.; Levin, Roy J.
    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 μm), hexamethonium (100 μm), tetrodotoxin (1.25 μm) and capsaicin (1 μm) 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 Nω-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.
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    Vagotomy inhibits the jejunal fluid secretion activated by luminal ileal Escherichia coli STa in the rat in vivo.
    (BMJ Publishing, 1999) Rolfe, Vivien E.; Levin, Roy J.
    BACKGROUND Escherichia coli heat stable enterotoxin (STa) is a major cause of secretory diarrhoea in humans. AIMS To assess the effects of instilling STa into the ileum on remote fluid secretion in the jejunum and colon in rats in vivo by a gravimetric technique. METHODS AND RESULTS Ileal STa (55 ng/ml) stimulated fluid secretion in both ileal and jejunal loops but not in the colon. The fluid secretion induced by ileal STa was inhibited by l-NAME (Nω -nitro-l-arginine methyl ester, 40 mg/kg intraperitoneally) but not by d-NAME (Nω -nitro-d-arginine methyl ester). Ileal carbachol (183 mg/ml) instilled into the lumen stimulated ileal secretion but not jejunal secretion, and was unaffected by l-NAME. Capsaicin (10 μM), instilled luminally with STa in the ileum, blocked both the ileal and jejunal fluid secretion. Acute bilateral vagotomy prevented luminal ileal STa from inducing jejunal fluid secretion but not from activating ileal fluid secretion. CONCLUSION IlealE coli STa stimulates remote secretion in the rat jejunum but not in the colon, probably by a nitrinergic, vagal reflex mediated by C fibres. This neural pathway will amplify the action of the toxin in its generation of secretory diarrhoea.