title: Peripheral corticotropin-releasing factor receptor type 2 activation increases colonic blood flow through nitric oxide pathway in rats.
abstract: BACKGROUND
  Corticotropin-releasing factor (CRF) peptides exert profound effects on the secretomotor function of the gastrointestinal tract. Nevertheless, despite the presence of CRF peptides and receptors in colonic tissue, their influence on colonic blood flow (CBF) is unknown.
  
  
  OBJECTIVE
  To determine the effect and mechanism of members of the CRF peptide family on CBF in isoflurane-anesthetized rats.
  
  
  METHODS
  Proximal CBF was measured with laser-Doppler flowmetry simultaneously with mean arterial blood pressure (MABP) measurement. Rats were injected with intravenous human/rat CRF (CRF1 > CRF2 affinity), mouse urocortin 2 (mUcn2, selective CRF2 agonist), or sauvagine (SVG, CRF2 > CRF1 affinity) at 1-30 µg/kg. The nitric oxide (NO) synthase inhibitor, L-NAME (3 mg/kg, iv), the cyclooxygenase inhibitor, indomethacin (Indo, 5 mg/kg, ip), or selective CRF2 antagonist, astressin2-B (Ast2B, 50 µg/kg, iv) was given before SVG injection (10 µg/kg, iv).
  
  
  RESULTS
  SVG and mUcn2 dose-dependently increased CBF while decreasing MABP and colonic vascular resistance (CVR). CRF had no effect on CBF, but increased CVR. The hyperemic effect of SVG was inhibited by L-NAME but not by Indo, whereas hypotension was partially reduced by L-NAME. Sensory denervation had no effect on SVG-induced changes. Ast2B inhibited SVG-induced hyperemia and decreased CVR, and partially reduced the hypotension.
  
  
  CONCLUSIONS
  Peripheral CRF2 activation induces colonic hyperemia through NO synthesis, without involving prostaglandin synthesis or sensory nerve activation, suggesting a direct action on the endothelium and myenteric neurons. Members of the CRF peptide family may protect the colonic mucosa via the activation of the CRF2 receptor.
authors.affiliation: CURE: Digestive Diseases Research Center; Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA, yakiba@mednet.ucla.edu.
authors.forename: Yasutada
authors.initials: Y
authors.lastname: Akiba
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kaunitz
authors.forename: Mulugeta
authors.initials: M
authors.lastname: Million
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002211:Capsaicin; D003106:Colon / Q000098:blood supply*; D003346:Corticotropin-Releasing Hormone / Q000819:agonists / Q000378:metabolism*; D006940:Hyperemia / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013152:Splanchnic Circulation; D014655:Vascular Resistance
chemical_list: C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D009569:Nitric Oxide; D003346:Corticotropin-Releasing Hormone; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester