Antiplatelet, antineutrophil and vasodilating properties of 13,14-dihydro-PGE1 (PGE0)--an in vivo metabolite of PGE1 in man.
The actions of the in vivo metabolite of PGE1, 13,14-dihydro-PGE1 (PGE0), on platelet and neutrophil (PMN) function and vessel tone were studied in vitro. PGE0 inhibited aggregation, ATP release and thromboxane generation by human platelets (IC50 10-100 nmoles/l). The compound also inhibited superoxide anion generation and lysosomal enzyme release from human PMN. PGE0 was equipotent to PGE1 in both systems, while 15-keto-PGE1 was ineffective in platelets but produced some inhibition in PMN. These inhibitory effects of PGE0 and PGE1 were paralleled by concentration-dependent increases in cyclic AMP in platelets and PMN. Both compounds were also potent relaxants of several arterial preparations in the rabbit at comparable concentrations. In general, the vasorelaxing properties of PGE0 were somewhat lower and the contractile effects somewhat stronger in comparison to PGE1. These data demonstrate a significant and concentration-dependent inhibition of receptor-mediated activation of human platelets and PMN by PGE0. The molar potency of the compound is comparable to that of PGE1. Generation of PGE0 from infused PGE1 may contribute to the clinical efficacy of PGE1 in treatment of severe peripheral arterial occlusive disease.
Ney
P
P
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Federal Republic of Germany.
Braun
M
M
Szymanski
C
C
Bruch
L
L
Schrör
K
K
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D010972:Platelet Activating Factor; D013481:Superoxides; C069881:13,14-dihydroprostaglandin E1; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005966:Glucuronidase; D000527:Alprostadil