Role of constitutive cyclooxygenase-2 in prostaglandin-dependent secretionin mouse colon in vitro

The relative contributions of cyclooxygenase (COX)-1 and COX-2 in mediating prostaglandin (PG)-dependent chloride secretion were investigated in segme nts of mouse colon mounted in Ussing-type diffusion chambers. COX-2 mRNA an d protein were constitutively expressed as shown by reverse transcription-p olymerase chain reaction and Western immunoblot, respectively. COX-2 immuno reactivity was detected immunohistochemically in cells lying subjacent to t he crypt epithelial cells. In segments of colon mounted in Ussing chambers, arachidonic acid caused a concentration-dependent increase in short-circui t current that was blocked by piroxicam, the COX-2 inhibitor NS-398, and th e COX-1 inhibitor SC-560. Exposure to the PG-dependent secretagogue, bradyk inin, 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 incub ated in the presence of 10 mu M arachidonic acid, segments of mouse colon p roduced both PGE(2) and PGD(2). 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-depe ndent electrolyte transport.