Lipid Metabolism in the Healthy and Disease Heart

The discovery of the second-messenger functions of on serine and threonine residues. Although there is inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3) and 1,2-dia- general agreement that PKC plays an important role in cylglycerol (DAG), the products of receptor-stimulated the initiation and/or modulation of receptor-linked re- phosphatidylinositol 4,5-bisphosphate (PtdIns( 4,5)P ) 2 sponses, the precise nature or molecular details of this hydrolysis, marked a turning point in the studies on the involvement remain elusive. There are several sugges- mechanisms of mediation of functional hormone and tions of possible functions of PKC, including involve- neurotransmitter responses. The historical background ment in modulation of ionconductance, regulation of of this discovery and the extensive bibliography of the receptor interaction with components of (other) signal 2 enormously expanding knowledge in this field was re- transduction pathways, modulation of Ca + sensitivity cently presented by Rana and Hokin [1], the latter of contractile proteins and gene expression [6]. author who first observed the phosphoinositide effect The receptors involved in the activation of the adeny- 35 years ago. It was, however, the Ca2+ gating hypothe- late cyclase and PtdIns cascade pathways have one com- sis proposed by Michell [2] on basis of a survey of mon feature. They are present in the plasmamembrane observations on the phosphoinositide turnover in a as complexes with GTP binding proteins (G-proteins).