Cyclosporin A inhibits PGE2 release from vascular smooth muscle cells.
The influence of the fungoid undecapeptide cyclosporin A (CyA) on PGE2 release from cultured rat aortic smooth muscle cells was investigated in this study. We found that CyA time and concentration dependently (ED50:500 ng/ml) inhibited PGE2 release from the cells. CyA attenuated both basal and PGE2 release evoked by angiotensin II (10(-10)-10(-6) M), arginine vasopressin (10(-10)-10(-6) M) and ionomycin (10(-9)-10(-6) M). CyA (1 microgram/ml) did not affect the conversion of exogenous arachidonic acid (1 microM) into PGE2. The inhibitory effect of CyA was neutralized by high concentrations of the calcium ionophore ionomycin (greater than 3 X 10(-6) M). Taken together our results indicate that CyA inhibits both basal and vasoconstrictor evoked PGE2 release from vascular smooth muscle by impairing the availability of free arachidonic acid rather than by inhibiting the conversion of arachidonic acid into PGE2.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001127:Arginine Vasopressin / Q000494:pharmacology; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology*; D015232:Dinoprostone; D004987:Ethers / Q000494:pharmacology; D015759:Ionomycin; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism*; D051381:Rats
D001095:Arachidonic Acids; D003524:Cyclosporins; D004987:Ethers; D011458:Prostaglandins E; D000804:Angiotensin II; D001127:Arginine Vasopressin; D016718:Arachidonic Acid; D015759:Ionomycin; D011451:Prostaglandin-Endoperoxide Synthases; D010740:Phospholipases; D015232:Dinoprostone