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INSERM, U-45, Hôpital Edouard Herriot (F.M., E.N.-G., P.P., J.C.C.), 69437 Lyon; Laboratoire de Physiologie et Pharmacologie, Université de Savoie (S.P.), 73376 Le Bourget du Lac; and Unité dEcologie et de Physiologie du Système Digestif, Institut National de la Recherche Agronomique (F.L., P.P., J.C.C.), 78352 Jouy-en-Josas, France
Address all correspondence and requests for reprints to: Dr. Jean-Claude Cuber, INSERM, U-45, Hôpital Edouard-Herriot, Pavillon Hbis, 69437 Lyon Cedex 03, France. E-mail: cuber{at}lyon151.inserm.fr
The intestinal peptide guanylin regulates the electrolyte/water transport in the intestinal epithelium. The aim of the present study was to investigate the mechanisms that modulate its secretion in the isolated vascularly perfused rat colon by using a specific guanylin RIA. Intraarterial infusion of bethanechol (10-4 M) or bombesin (10-7 M) elicited a significant 6-fold increase in the release of guanylin immunoreactivity (G-IR) in the lumen. Bombesin-stimulated G-IR secretion was strongly reduced by tetrodotoxin, whereas atropine had no effect. VIP (10-7 M) induced a moderate release of G-IR, whereas substance P, calcitonin gene-related peptide, peptide YY, somatostatin, and neurotensin were without effect. Dimethyl-PGE2 (1.4 x 10-5 M) or interleukin-1ß (2.5 x 10-10 M) induced a 3-fold increase in G-IR in the lumen, whereas the degranulator compound bromolasalocid did not stimulate guanylin secretion. Forskolin (10-5 M) or sodium nitroprusside (10-410-3 M) induced a significant release of G-IR. In contrast, PMA (10-7 M) or ionophore A23187 (10-6 M) did not modify basal secretion of G-IR. Upon stimulation of guanylin release with bombesin or bethanechol, an increase in G-IR in the portal effluent was also detected. The release of G-IR in the portal effluent was 40-fold lower than that of G-IR into the luminal perfusate. Additionally, analysis with gel chromatography revealed that the immunoreactive material released in the lumen or in the portal effluent coeluted with the 15-amino acid peptide originally isolated from rat intestine. In conclusion, the present data suggest that the enteric nervous system and immune cells may modulate guanylin release from the rat colon. The release of guanylin in the lumen and portal effluent suggests that this peptide may exert both luminal/paracrine and hormonal effects.
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