NoThe study investigated the role of endothelin (ET) and the ET receptor subtypes ETA and ETB in mediating longitudinal contraction in the mouse proximal and distal colon.\ud Cumulative concentration¿response curves to a range of ET agonists (ET-1, ET-2, ET-3, (Ala1,3,11,13) ET and IRL 1620) were established by administering concentrations ranging from 0.01nM to 0.3¿M. Concentration¿response curves to ET-1, which exhibits a high affinity for both ETA and ETB receptor subtypes, were also established in the presence of the ETA antagonist BMS 182874 and the ETB antagonist IRL1038.\ud The addition of the selective ETA receptor antagonist BMS 182874 caused a rightward shift of the concentration¿response curve to ET-1 in both sections of the colon. The ETB receptor antagonist IRL1038 (0.3¿1¿M) did not significantly effect the response to ET-1 in the proximal colon but caused a significant decrease in response towards higher concentrations ranges (3nM) in the distal colon.\ud A comparison of the concentration¿response curves to ET-1, ET-2 and ET-3 showed a rank order of potency ET-1ET-2ET-3 in the proximal colon and ET-1ET-2ET-3 in the distal colon. The selective ETB receptor agonists, (Ala1,3,11,13) ET and IRL 1620 did not produce any response in the proximal sections of the colon but produced a smaller contraction in the distal segments.\ud The data indicate that ET can contract the proximal tissues of the mouse colon predominantly via ETA receptors and in the distal tissues via ETA and ETB receptors
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