PROTEIN-KINASE-C IS NOT INVOLVED IN THE DESENSITIZATION OF PLATELET-ACTIVATING-FACTOR RECEPTOR IN RABBIT PLATELETS

Rabbit platelets pretreated with platelet activating factor (PAF) became refractory to further stimulation by PAF. The effect was specific for PAF. In this study, the alteration in the specific agonist binding to PAF receptor in platelets following desensitization was investigated. As revealed by the Scatchard analysis of radio-ligand binding data, the affinity for specific PAF binding to desensitized platelet membranes was substantially lowered as compared with that to control platelet membranes. Guanine nucleotide triphosphate, which was shown to decrease the affinity of specific PAF binding to platelet membranes, had less effect on the PAF binding affinity to the desensitized preparation. In platelets pretreated with phorbol 12-myristate-13-acetate, the binding affinity of PAF receptor remained unaltered. Pretreatment of platelets with 1-(5-isoquinolinesulphonyl)-2-methylpiperazine, a protein kinase C inhibitor, or neomycin, an inhibitor of the polyphosphoinositide breakdown, failed to prevent the reduction of specific PAF binding affinity following subsequent exposure to PAF. These results suggest that the agonist-induced desensitization of PAF receptor in rabbit platelets is independent of activation of protein kinase C.