Nitric oxide but not prostacyclin is an autocrine endothelial mediator.
Using porcine aortic endothelial cells, the present study investigates whether stimulation of prostacyclin (PGI2) and nitric oxide also causes elevation of the respective second messengers cAMP and cGMP in the endothelial generator cells. The calcium ionophore A23187 at 0.3-3 microM increased endothelial cGMP levels up to 27-fold in an L-arginine-dependent manner as assessed through complete inhibition by NG-monomethyl-L-arginine (100 microM). The 36-fold PGI2 stimulation by 3 microM A23187 was not accompanied by an intracellular increase in cAMP or an enhanced cAMP efflux. Correspondingly, the PGI2 mimetic iloprost (10 pM-100 microM) did not change endothelial cAMP levels. However, forskolin (1-100 microM) and prostaglandin E2 (PGE2) (0.1-10 microM) produced concentration-dependent increases in cAMP with a 9-fold and 8-fold stimulation at 100 microM forskolin and 10 microM PGE2, respectively. These results demonstrate that in contrast to NO, PGI2 acts as a strictly paracrine hormone without affecting the respective second messenger cAMP in the endothelial generator cells.
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Federal Republic of Germany.
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D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D015232:Dinoprostone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D016285:Iloprost / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects; D013552:Swine; D019323:omega-N-Methylarginine
D005576:Colforsin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; D001120:Arginine; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP; D016285:Iloprost; D015232:Dinoprostone