Platelet-activating factor and analogues: comparative studies with human neutrophils and rabbit platelets.
Platelet-activating factor and 12 structural analogues stimulated rabbit platelets to aggregate and release [14C]-serotonin. They likewise caused human neutrophils to aggregate, degranulate, and take up [3H]-deoxyglucose. Their respective potencies, which varied by 4-5 orders of magnitude, correlated highly (r greater than or equal to 0.93) in all assays. These compounds also selectively desensitized neutrophils to the degranulating actions of platelet-activating factor but not to C5a or a formylated oligopeptide. Three other analogues with structures quite similar to platelet-activating factor were unable to activate or desensitize the cells. Hence, the structure-activity relations of the analogues in several assays of platelet and neutrophil function were similar and they stimulated neutrophils by a common activation mechanism that differed from those used by C5a or formylated oligopeptides. These data are consistent with the notion that platelet-activating factor activates and desensitizes various target cells through stereospecific receptors. Apparently, these putative receptors on neutrophils and platelets have similar structural specificities for platelet-activating factor and its analogues.
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002449:Cell Aggregation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005997:Glycerylphosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D012701:Serotonin / Q000502:physiology; D013329:Structure-Activity Relationship
D010972:Platelet Activating Factor; D012701:Serotonin; D005997:Glycerylphosphorylcholine