TY - JOUR T1 - Role of Constitutive Cyclooxygenase-2 in Prostaglandin-Dependent Secretion in Mouse Colon In Vitro JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 539 LP - 544 VL - 293 IS - 2 AU - Wallace K. MacNaughton AU - Kelly Cushing Y1 - 2000/05/01 UR - http://jpet.aspetjournals.org/content/293/2/539.abstract N2 - 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 PGE2but 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. The American Society for Pharmacology and Experimental Therapeutics ER -