Platelet aggregation induced by ether-linked phospholipids. 2. Mechanism of desensitization of rabbit platelets by platelet activating factor and reversibility of inhibitory actions of its antagonists.
Rabbit platelets pretreated with CV-3988 had reduced responsiveness to platelet activating factor(PAF) even after the platelets had been washed with a buffer. This was due to its tight binding to receptor sites for PAF, but not conformational changes of the receptor, because the platelets that were pretreated with CV-3988 and then washed with buffer containing 0.5% bovine serum albumin showed full responsiveness to PAF. In contrast, the reduced responsiveness of PAF-pretreated rabbit platelets was not reversed by washing with buffer containing 0.5% BSA. The PAF-pretreated platelets showed significantly lower responsiveness to 1-O-hexadecyl-2-O-monomethylaminocarbonyl-sn-glycero-3-phosphochol ine (MC-PAF) than to PAF, although MC-PAF had the same potency as PAF on inducing aggregation of normal rabbit platelets by interacting with receptor sites for PAF. These results suggest that the desensitization is accompanied by a decreased affinity of receptor sites for PAF or reduced efficiency in coupling of activated receptor to regulatory protein in plasma membranes rather than loss of receptor sites.
D000818:Animals; D066298:In Vitro Techniques; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000494:pharmacology
D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D013844:Thiazoles; D012710:Serum Albumin, Bovine; C037913:CV 3988; C048549:ONO 6240