Desensitisation and Potentiation of Platelet Inositol Phospholipid Hydrolysis

[摘要] I attempted to clarify the role of receptor stimulated phosphoinositide hydrolysis in mediating the activity of a number of agonists whose putative mechanism of action was unknown or controversial. Phosphoinositide hydrolysis was routinely monitored by measuring the formation of [32P] phosphatidic acid (Ptd OH) in platelets prelabelled with [32P] orthophosphate. Ptd OH is the phosphorylated product of DAG, and the experimental conditions adopted allowed [32P] Ptd OH to obtain isotopic equilibrium with gamma-[32P] ATP such that changes in label reflect changes in Ptd OH content. In addition in some studies depletion of [32P] PIP2 was monitored. Cytosolic free calcium concentration was measured by Quin 2. In addition, I evaluated the role of various putative endogenous mediators of desensitisation on the stimulatory transduction process(es) and addressed the possible mechanism(s) whereby agonist-induced platelet reactivity could be potentiated.

[发布机构] University:University of Glasgow

[关键词] Pharmacology