title: Corticotropin-releasing factor inhibition of sheep fetal colonic contractility: mechanisms to prevent meconium passage in utero.
abstract: OBJECTIVE
  In humans, fetal in utero meconium (MEC) passage rarely occurs before term gestation. We hypothesized the existence of inhibitory mechanism(s) preventing colonic motility and MEC passage prior to term.
  
  
  METHODS
  Longitudinal smooth muscle strips prepared from distal colon of preterm ovine fetuses (130-132 d; term = 148-152 d) were examined for their contractile responses to muscarinic receptor agonist (bethanechol) and both nonspecific (atropine) and receptor subtype specific antagonists (M1: pirenzepine dihydrochloride, M2 methoctramine, M3: 4-diphenylacetoxy-N-methlpiperidine methiodide [4-DAMP] and M4: tropicamide) in an in vitro organ bath system. Effects of corticotrophin releasing factor (CRF) and Urocortin I (URO-I), known modulators of colonic motility and smooth muscle contractility, were studied on bethanechol-induced contractility. Immunohistochemical analysis was performed to confirm the expression of CRF and URO-I, and muscarinic and CRF R2 receptors in distal colon.
  
  
  RESULTS
  Bethanechol induced smooth muscle contractions via muscarinic receptor subtype M3. CRF and URO-I elicited a significant inhibition of bethanechol induced contraction. Immunohistochemical analysis verified the expression of muscarinic receptor subtype M3, CRF, URO-I and CRF-receptor-R2 in distal colon.
  
  
  CONCLUSIONS
  Inhibition of M3 dependent distal colonic motility by CRF system may prevent the passage of MEC in the preterm ovine fetus.
authors.affiliation: Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Jayaraman
authors.initials: J
authors.lastname: Lakshmanan
authors.forename: Noboru
authors.initials: N
authors.lastname: Oyachi
authors.forename: Sureshbabu A
authors.initials: SA
authors.lastname: Ahanya
authors.forename: Guiong
authors.initials: G
authors.lastname: Liu
authors.forename: Momeni
authors.initials: M
authors.lastname: Mazdak
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ross
mesh_terms: D000818:Animals; D018723:Bethanechol / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus; D005769:Gastrointestinal Motility / Q000187:drug effects; D007150:Immunohistochemistry; D008470:Meconium / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010890:Pirenzepine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal; D011336:Probability; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012680:Sensitivity and Specificity; D034561:Sheep, Domestic; D046509:Tissue Culture Techniques
chemical_list: D018721:Muscarinic Agonists; D018019:Receptors, Corticotropin-Releasing Hormone; D018723:Bethanechol; D010890:Pirenzepine