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Vol. 293, Issue 2, 539-544, May 2000

Role of Constitutive Cyclooxygenase-2 in Prostaglandin-Dependent Secretion in Mouse Colon In Vitro1

Wallace K. MacNaughton2 and Kelly Cushing

Gastrointestinal Research Group and Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada

The relative contributions of cyclooxygenase (COX)-1 and COX-2 in mediating prostaglandin (PG)-dependent chloride secretion were investigated in segments of mouse colon mounted in Ussing-type diffusion chambers. COX-2 mRNA and protein were constitutively expressed as shown by reverse transcription-polymerase chain reaction and Western immunoblot, respectively. COX-2 immunoreactivity was detected immunohistochemically in cells lying subjacent to the crypt epithelial cells. In segments of colon mounted in Ussing chambers, arachidonic acid caused a concentration-dependent increase in short-circuit current that was blocked by piroxicam, the COX-2 inhibitor NS-398, and the COX-1 inhibitor SC-560. Exposure to the PG-dependent secretagogue, bradykinin, also caused an increase in short-circuit current that was not blocked by piroxicam or SC-560, and only by the highest dose of NS-398. When incubated in the presence of 10 µM arachidonic acid, segments of mouse colon produced both PGE2 and PGD2. Synthesis of PGE2 but not PGD2 was blocked by NS-398 and SC-560. These data demonstrate that both COX-1 and COX-2 are constitutively expressed in the mouse colon, and both contribute to PG-dependent electrolyte transport.

1 This study was supported by a New Investigator Establishment grant from the Canadian Association of Gastroenterology and the Medical Research Council of Canada.

2 W.K.M. is an Alberta Heritage Foundation for Medical Research Scholar.

0022-3565/00/2932-0539$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


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eLetters:

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Constitutive cox-2 ?
Islam Khan
JPET Online, 12 Jun 2000 [Full text]
Response to eLetter from Islam Khan re "Constitutive cox-2?"
Wallace MacNaughton, Ph.D.
JPET Online, 12 Jun 2000 [Full text]

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