Thromboxane A2 receptor linked with the Ca2+ pathway in rat colonic crypt cells.
To clarify the presence of thromboxane A2 (TXA2) receptor in the colonic epithelium, we examined the effect of 9,11-epithio-11, 12-methano-thromboxane A2 (STA2), a stable analogue of TXA2, on intracellular free Ca2+ concentration ([Ca2+]i) of indo-1-loaded single cells in isolated rat colonic crypts by laser confocal microscopy. STA2 increased [Ca2+]i in a concentration-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 STA2-induced increase in [Ca2+]i was completely blocked by two selective TXA2 receptor antagonists, KW-3635 and ONO-3708. These antagonists did not affect both the basal [Ca2+]i and the carbaco-induced increase in [Ca2+]i. Prostaglandin E2 did not increase [Ca2+]i. These results indicate that the STA2-elicited increase in [Ca2+]i is mediated specifically by a TXA2 receptor in colonic crypt cells This is the first report showing the presence of a TXA2 receptor that is associated with Ca2+ mobilization in the colon.
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001584:Benzoxepins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000819:agonists / Q000378:metabolism*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology