The signal transduction of prostaglandin E
2 (PGE
2) and thromboxane A
2 (TXA
2), cyclooxygenase products of arachidonic acid, was investigated in smooth muscle preparations and 1321N1 human astrocytoma cells. While PGE
2 has been known to stimulate (via EP
2 receptor) or inhibit (via EP
3 receptor) adenylate cyclase, PGE
2 activated phosphatidylinositol 4, 5-bisphosphate (PIP
2)-specific phospholipase C (PLase C) in non-vascular smooth muscles (via EP
1 receptor), resulting in accumulations of inositol trisphosphate (IP
3) and diacylglycerol to elicit intracellular Ca
2+ mobilization. On the other hand, STA
2, a TXA
2 receptor analogue, also accumulated IP
3 in human astrocytoma cells. [
3H]SQ 29548, a TXA
2 receptor antagonist, specifically bound to astrocytoma membranes. TXA
2-receptor antagonists (ONO NT-126, S-145, SQ29548 and ONO3708) concentration-dependently inhibited PIP
2-specific PLase C activation by STA
2, and they also inhibited [
3H] SQ 29548 binding in human astrocytoma cells. The Ki value of each antagonist in PIP
2-specific PLase C inhibition was similar to that in [
3H]SQ29548 binding inhibition. In membrane preparations, STA
2 activated PIP
2-specific PLase C in the presence of GTPγS. Pertussis toxin (IAP) did not affect STA
2-induced PLase C activation. The results suggest that stimulation of TXA
2 receptors activates PIP
2-specific PLase C via an IAP-insensitive G-protein.
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