COLONIC MUCIN DISCHARGE BY A CHOLINERGIC AGONIST, PROSTAGLANDINS, ANDPEPTIDE YY IN THE ISOLATED VASCULARLY PERFUSED RAT COLON

The model of the isolated, vascularly perfused rat colon was assessed in the present study to investigate the nervous, hormonal, and local/p aracrine pathways involved in colonic mucin secretion. A colonic loop was perfused via the superior mesenteric artery with a Krebs-Henseleit buffer containing 25% washed bovine erythrocytes at a rate of 2.5 ml/ min. After a 10-min control period, each compound to be tested was inf used intra-arterially for 30 min. Tissue samples from the proximal and midsegments of the perfused rat colon were then fixed and stained for mucus cell count. Intra-arterial administration of bethanechol evoked a concentration-dependent decrease in the number of stained mucus cel ls per crypt section over the range 2.10(-6) to 2.10(-4) M: 16.6 +/- 1 .4 stained mucus cells per crypt in the midportion of the perfused rat colon (n = 5) with bethanechol 2.10(-4) M versus 28.8 +/- 1.5 for con trols (n = 6). After infusion of 1.25 and 2.5 mu M 16,16-dimethyl pros taglandin E-2 (dmPGE(2)), the number of stained mucus cells per crypt section was significantly reduced: 21.6 +/- 0.6 (n = 6) and 20.6 +/- 1 .4 (n = 7), respectively. An increase in the number of cavitated mucus cells was also observed (22.1 -/+ 6.7 and 38.5 +/- 4.1% of cavitated mucus cells in the midsegment of the perfused rat colon with 1.25 and 2.5 mu M dmPGE(2), respectively, vs. 12.3 +/- 4.1% for controls). In c ontrast, prostaglandin F-2 alpha did not significantly affect mucus di scharge from colonic cells. Peptide YY (10(-10), 10(-9) and 10(-8) M) induced a dose-dependent increase in the percentage of cavitated mucus cells (16.7 +/- 2.8, 23.1 +/- 4.2, and 31.2 +/- 3.4% of cavitated muc us cells in the midsegment, respectively). The proximal and midsegment s of the perfused rat colon were equally sensitive to each secretagogu e. Conclusion: In the isolated, vascularly perfused rat colon, mucus c ells strongly respond to the well-known mucin secretagogues, bethanech ol and dmPGE(2). This approach has already led to the identification o f a novel stimulant of mucin secretion: peptide YY. Our ex vivo model, in which goblet cells are submitted to well-defined luminal and blood -borne stimuli is, therefore, reliable to investigate the nervous, hor monal, and local/paracrine pathways involved in the colonic mucin secr etion.