Constitutive expression and function of cyclooxygenase-2 in murine gastric muscles.
OBJECTIVE
Cyclooxygenase enzymes (COX) generate intermediates in the prostaglandin (PG) cascade. COX-1 is constitutively expressed in many cells, and COX-2 is typically thought to be an inducible isoform.


METHODS
We evaluated constitutive expression and function of COX-2 in murine gastric muscles.


RESULTS
Immunohistochemistry showed COX-2-like immunoreactivity (COX-2-LI) in myenteric neurons. Half the neurons with COX-2-LI expressed nitric oxide synthase (NOS). COX-2-LI was not observed in smooth muscle cells. Interstitial cells of Cajal within muscle layers (IC-IM) expressed COX-2-LI, suggesting a novel role for IC-IM. Molecular studies verified expression of COX-2 in gastric muscles. Quantitative polymerase chain reaction (PCR) showed equal expression of COX-1 and COX-2 in the antrum. COX-2 was more abundant in fundus. Indomethacin and GR253035X, a COX-2 inhibitor, increased antral phasic contractions and potentiated responses to ACh. Indomethacin, but not GR253035X, increased contractions and potentiated responses in tissues of COX-2 knockout mice. Indomethacin and GR253035X reduced tone in the fundus.


CONCLUSIONS
COX-2 is constitutively expressed by IC-IM and neurons in the stomach and at levels similar to COX-1. Prostanoids produced by COX-2 regulate mechanical activities of fundus and antral muscles.
Porcher
Christophe
C
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
Horowitz
Burton
B
Bayguinov
Orline
O
Ward
Sean M
SM
Sanders
Kenton M
KM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D051546:Cyclooxygenase 2; D005260:Female; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000032:analysis; D009599:Nitroprusside / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D013270:Stomach / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology
D007527:Isoenzymes; D012333:RNA, Messenger; D009599:Nitroprusside; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine; D007213:Indomethacin