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 145-trisphosphate (Ins(145)P 3) and 12-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 45-bisphosphate (PtdIns( 45)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).