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Localization and gestation‐dependent pattern of corticotrophin‐releasing factor receptor subtypes in ovine fetal distal colon
Author(s) -
Lakshmanan J.,
Magee T. R.,
Richard J. D.,
Liu G. L.,
Salido E.,
Sugano S. K.,
Ferrini M.,
Ross M. G.
Publication year - 2008
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2008.01209.x
Subject(s) - receptor , endocrinology , medicine , biology , fetus , muscularis mucosae , gestation , meconium , motility , anatomy , microbiology and biotechnology , pregnancy , genetics
Meconium passage is frequently observed in association with feto‐maternal stress factors such as hypoxia and infection, but the triggering mechanism is unknown. We hypothesize that differential regulation of corticotrophin‐releasing factor (CRF) receptors during gestation play an important role in determining the susceptibilities of the fetus to stress‐induced in utero meconium passage at term. We examined the innervation patterns of CRF‐receptor type 1 (CRF‐R1), a stimulator of gastrointestinal motility and CRF‐receptor type II (CRF‐R2), an inhibitor of gastrointestinal motility in ovine fetal distal colonic segments from very preterm to term gestation. Both CRF‐R1 and CRF‐R2 receptors were present in muscularis mucosa as well as in longitudinal and circular smooth muscle layers in fetal distal colonic segments at all gestational ages. Quantitative image analysis indicated a 42% increase in CRF‐R1 receptor immunoreactivity in muscularis mucosa and a 30% in longitudinal smooth muscle layers from very preterm to term. In contrast, CRF‐R2 receptor immunoreactivity in muscularis mucosa as well as in longitudinal and circular smooth muscle layers decreased by 38%, 55% and 51%, respectively, at term. The percentage of enteric ganglia and the number of enteric neurons expressing CRF‐R1 receptors were high at term. Western blot analysis identified 235 and 50 kDa molecular species of CRF‐R1 receptors and 37 and 28 kDa molecular species of CRF‐R2 receptors. In summary, we speculate that downregulation of CRF‐R2 receptor abundance with concurrent increases in CRF‐R1 receptor levels in myenteric‐smooth muscle unit with advancing gestation sensitizes the colonic motility responses to stressors.