Effects of prostacyclin analogue (carbacyclin) on the interaction of platelets with different collagen substrates. Inhibition of cAMP increase by collagens type I, III, and IV.
We investigated the effects of a stable prostacyclin analogue, carbacyclin, on the interaction of platelets with collagen substrates differing in their ability to activate platelets: human collagens type I, III, IV and V (CI, CIII, CIV and CV), and commercial calf skin collagen type I (CSC). The total adhesion was measured using 51Cr-labelled platelets, and quantitative morphometry of adherent platelets was performed by scanning electron microscopy (SEM). Carbacyclin in the concentrations inducing a 10-fold rise in platelet cAMP did not affect the adhesion of platelets to weak substrates, CV and CSC, but reduced the adhesion to strong substrates, CIV (by 49%) and CI/CIII (by 78%), which stimulated massive spreading and formation of surface-bound aggregates respectively. Carbacyclin inhibited all morphological manifestations of platelet activation associated with adhesion: conversion of native discoid platelets to spherical ones on CSC; massive spreading on CIV; and aggregate formation on CI/CIII. Massive spreading and aggregation on a weak substrate (CSC) stimulated by arachidonic acid and thrombin was also inhibited by carbacyclin. Under the same concentration of agonists aggregation of platelets was more sensitive to the action of carbacyclin, than spreading. Strong collagen substrates CI, CIII and CIV, but not CV and gelatin, inhibited the carbacyclin-induced rise in platelet cAMP.
Mazurov
A V
AV
USSR Cardiology Research Center, Moscow.
Misselwitz
F
F
Hoffman
U
U
Leytin
V L
VL
Repin
V S
VS
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D003094:Collagen / Q000494:pharmacology / Q000502:physiology*; D000242:Cyclic AMP / Q000097:blood*; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011465:Prostaglandins, Synthetic; C026678:carboprostacyclin; D003094:Collagen; D011464:Epoprostenol; D000242:Cyclic AMP