Development of ovine fetal ileal motility: role of muscarinic receptor subtypes

Abstract Objective In the preterm human fetus, immaturity of gastrointestinal (GI) motility contributes to impairment of oral feeding and an increased risk of necrotizing enterocolitis. In view of the limited knowledge of fetal GI motility development, and the primary role of the muscarinic system in adult GI motility, we examined the development of GI muscarinic receptor subtypes associated with ileal motility. Study design Ovine term fetal, newborn, and pregnant adult ileal longitudinal muscle contractile responses to muscarinic agonists (bethanechol) and muscarinic nonspecific (atropine) and subtype specific-antagonists (M1-M4) were examined in organ baths. Immunohistochemical analysis of ileal muscle muscarinic receptor subtypes was correlated with contractile responses. Results Bethanechol induced a concentration-dependent ileal contraction at all 3 age groups. Adult ileal maximal tension was 2-fold higher than that of the fetus and newborn, while 50% effective concentration (EC 50 ) was similar at all ages. Atropine (10 −6 mol/L) inhibited contractility in fetal (67%±7%), newborn (82%±5%), and adult (97%±2%) in an age-dependent manner. The M3 antagonist exhibited robust inhibition at all age groups while the M2 antagonist demonstrated enhanced inhibition in the fetus. Immunohistochemical analysis indicated coexpression of subtype receptors in fetal, newborn, and adult ileal smooth muscle with increasing expression with advancing age. Conclusion These results demonstrate a specific developmental pattern of muscarinic receptor subtype expression. Knowledge and/or alterations of GI motility regulation may aid in the treatment of the preterm fetus or newborn.