Release of guanylin immunoreactivity from the isolated vascularly perfusedrat colon

The intestinal peptide guanylin regulates the electrolyte/water transport i n the intestinal epithelium. The aim of the present study was to investigat e the mechanisms that modulate its secretion in the isolated vascularly per fused 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, wh ereas atropine had no effect. VIP (10-7 M) induced a moderate release of G- IR, whereas substance P, calcitonin gene-related peptide, peptide YY, somat ostatin, and neurotensin were without effect. Dimethyl-PGE(2) (1.4 x 10(-5) M) or interleukin-1 beta (2.5 x 10(-10) M) induced a 3-fold increase in G- IR in the lumen, whereas the degranulator compound bromolasalocid did not s timulate guanylin secretion. Forskolin (10(-5) M) or sodium nitroprusside ( 10(-4)10(-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 i ncrease 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 lumi nal perfusate. Additionally, analysis with gel chromatography revealed that the immunoreactive material released in the lumen or in the portal effluen t coeluted with the 15-amino acid peptide originally isolated from rat inte stine. In conclusion. the present data suggest that the enteric nervous sys tem and immune cells may modulate guanylin release from the rat colon. The release of guanylin in the lumen and portal effluent suggests that this pep tide may exert both luminal/paracrine and hormonal effects.