C3a and C5a were investigated for their ability to induce secretion of serotonin from platelets in a homologous guinea pig system. Platelets respond to either anaphylatoxin with a dose-dependent release that does not exceed a plateau at the 70% level. On a molar basis. C5a is about 50-fold more active than the C3 fragment. The C5a effects in the platelet system can be clearly distinguished from the activity of C3a and vice versa by a phenomenon of specific desensitization of the platelets to either stimulus. Our observations lead to the postulation of distinct receptors for C3a and C5a on guinea pig platelets as well as 2 independent pathways of platelet activation, which both lead to a specific release.
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