Effects of pituitary adenylate cyclase-activating polypeptide on the cyclooxygenase pathway of rat platelets and on platelet aggregation.
Several data suggest that pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in the regulation of local circulation. One possible role of PACAP in the regulation of circulation is that, it may modify the cyclooxygenase pathway of the arachidonate cascade in platelets. Our study was designed to study the effect of PACAP on the cyclooxygenase pathway of rat platelets and on platelet aggregation. PACAP (10(-7) and 10(-6) M) significantly inhibited the cyclooxygenase pathway of platelets, mostly the thromboxane synthesis. Pretreatment with a PACAP receptor antagonist, PACAP(6-38), or with an inhibitor of protein kinase A, H-89, shows that the effects of PACAP on the cyclooxygenase pathway were diminished. In the aggregation studies, PACAP inhibited both the arachidonic acid-induced and the thrombin-induced platelet aggregation. It can be concluded that PACAP inhibits the cyclooxygenase pathway of rat platelets via a specific PACAP receptor-activated, cAMP-dependent pathway, and these effects of PACAP are involved in the inhibition of platelet aggregation.
Kis
B
B
Department of Pathophysiology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Mezei
Z
Z
Dancsó
G
G
Pataricza
J
J
Gecse
A
A
Papp
J G
JG
Telegdy
G
G
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010974:Platelet Aggregation / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors; D013449:Sulfonamides; D013928:Thromboxane A2 / Q000378:metabolism
C495403:Adcyap1 protein, rat; D007546:Isoquinolines; D009479:Neuropeptides; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011453:Prostaglandins; D047428:Protein Kinase Inhibitors; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D013449:Sulfonamides; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); D013928:Thromboxane A2; D000242:Cyclic AMP; D011451:Prostaglandin-Endoperoxide Synthases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide