Pharmacology of phosphoinositides, regulators of multiple cellular functions

Inositol phospholipids represent a small fraction of the phospholipids pres ent in all cellular membranes with remarkable importance in regulating vari ous cell functions. They are synthesized from phosphatidylinositol by seque ntial phosphorylations on the several hydroxyls of the inositol ring to cre ate polyphosphoinositides that function either as docking sites to promote formation of molecular signaling complexes, or serve as precursors for solu ble inositol polyphosphates that act as diffusible intracellular messengers . Phosphoinositides are involved in the control of many processes, includin g membrane traffic, endo- and exocytosis, mitogenesis and apoptosis. Pharma cological tools have helped to clarify many details of phosphoinositide met abolism and have unveiled the roles of these lipids in the control of speci fic signaling pathways. However, because of their pleiotropic functions it has been questionable whether pharmacological manipulation of inositide for mation and metabolism can be of therapeutic value. This review briefly summ arizes the means by which inositide functions have been pharmacologically m anipulated, and discusses possibilities for specifically targeting certain aspects of their regulatory functions.