Thromboxane A(2) receptor linked with the Ca2+ pathway in rat colonic crypt cells

To clarify the presence of thromboxane A(2) (TXA(2)) receptor in the coloni c epithelium, we examined the effect of 9,11-epithio-11,12-methano-thrombox ane A(2) (STA(2)), a stable analogue of TXA(2), on intracellular free Ca2concentration ([Ca2+](i)) of indo-1-loaded single cells in isolated rat col onic crypts by laser confocal microscopy. STA(2) increased [Ca2+](i) in a c oncentration-dependent manner with a transient peak phase and a subsequent plateau phase. The EC50 values at peak and plateau phases were 1 and 32 nM, respectively. The STA(2)-induced increase in [Ca2+](i) was completely bloc ked by two selective TXA(2) receptor antagonists, KW-3635 and ONO-3708. The se antagonists did not affect both the basal [Ca2+](i) and the carbaco-indu ced increase in [Ca2+](i). Prostaglandin E-2 did not increase [Ca2+](i). Th ese results indicate that the STA(2)-elicited increase in [Ca2+](i) is medi ated specifically by a TXA(2) receptor in colonic crypt cells This is the f irst report showing the presence of a TXA(2) receptor that is associated wi th Ca2+ mobilization in the colon. (C) 1999 Academic Press.