Lipid second messengers derived from glycerolipids and sphingolipids, and their role in smooth muscle function

The processes that link activation of an external receptor to the internal mechanisms that elicit a physiological response have been the subject of ex tensive investigation. It has been established that rather than just being an inert barrier to protect the cell from environmental damage, there are p opulations of phospholipids located within the plasma membrane that act as a reservoir for signalling molecules and when a receptor binds its appropri ate activating ligand a chain of events is initiated which leads to the bre akdown of these lipids and the release of second messengers. Such processes are rapid enough for physiological responses to be effected. The purpose o f this review is to examine the profile of lipid second messengers derived from glycerophospholipids and sphingolipids. In the former class are includ ed phosphoinositide and phosphatidylcholine and the latter includes sphingo myelin. Hydrolysis of such parent compounds is mediated by phospholipases a nd the profile of metabolites appears to be agonist specific and modulated by a number of mechanisms including heterotrimeric G-protein subunits, smal l G-proteins. alterations in intracellular calcium concentration, protein k inase C and tyrosine kinases. The recent interest in sphingolipids, particu larly in vascular smooth muscle cells, has been provoked by the observation that ceramide and sphingoid base formation is observed in response to vaso constrictor hormones.