T E Bross

Phosphoinositide turnover provides a link in stimulus—response coupling

Abstract Much excitement has resulted from the discovery that phosphatidylinositol and its phosphorylated derivatives are storage forms of messenger molecules that can be released in response to specific extracellular signals. Signal molecules bind to cell surface receptors and the messenger molecules derived from the phosphoinositides couple the signal to a variety of responses within and between cells.

RHC 80267 does not inhibit the diglyceride lipase pathway in intact platelets

RHC 80267 inhibits diglyceride lipase activity in microsomes from canine platelets (1). Chau and Tai (2) reported that RHC 80267 prevents the transient accumulation of monoglyceride in thrombin-stimulated human platelets, while leaving arachidonate release unimpaired. In contrast, we find that while the drug inhibits both diglyceride lipase (I50 = 15 microM) and monoglyceride lipase (I50 = 11 microM) activities in platelet microsomes, it is ineffective when added to intact platelets. The transient intermediates in the diglyceride lipase pathway, 1,2-diglyceride and 2-monoglyceride, both accumulated after thrombin stimulation of intact platelets treated with RHC 80267, and arachidonate release was not inhibited. We conclude that RHC 80267 cannot be used to evaluate the diglyceride lipase pathway in intact platelets.