Developmental changes in response to endothelins and receptor subtypes of isolated rat duodenum

The response of isolated duodenum to endothelin-1, -3 and IRL 1620 (Suc-[Glu9,Ala11,15]endothelin-1 (8-21)), a selective endothelin ETB receptor agonist, was studied in both neonatal (1-week-old) and adult rats by recording mechanical activity isotonically. Endothelin-1, -3 and IRL 1620 (1-100 nM) elicited sustained contraction of neonatal duodenum, in a concentration-dependent manner, with a potency order of endothelin-1 = endothelin-3 > IRL 1620. The response to endothelin-1 and -3 (10-1000 nM) of adult duodenum was biphasic, i.e., transient relaxation followed by contraction, with a potency order of endothelin-1 > endothelin-3. The contractile response to endothelin-1 of adult but not neonatal duodenum was significantly antagonized by pretreatment with FR139317 (1 microM), an endothelin ETA receptor antagonist. An endothelin ETB receptor antagonist, RES-701-1 (3 microM), weakly antagonized the IRL 1620-induced contraction of neonatal duodenum. However, RES-701-1 (10 microM) did not affect the response to endothelin-1 of either adult or neonatal duodenum. These results indicate that the duodenal response to endothelins changes from a sustained contraction in neonates to a biphasic response in adults. The contractile response to endothelins of neonatal duodenum is suggested to be mediated through endothelin ETB receptors or possibly RES-701-1-resistant ETB receptor subtypes and contraction of adult duodenum through endothelin ETA receptors. The mechanism of the endothelin-induced response of duodenum was also studied.