Corticotropin-releasing factor inhibition of sheep fetal colonic contractility: mechanisms to prevent meconium passage in utero.
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.
Lakshmanan
Jayaraman
J
Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA, USA.
Oyachi
Noboru
N
Ahanya
Sureshbabu A
SA
Liu
Guiong
G
Mazdak
Momeni
M
Ross
Michael G
MG
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
D018721:Muscarinic Agonists; D018019:Receptors, Corticotropin-Releasing Hormone; D018723:Bethanechol; D010890:Pirenzepine