Second Messenger Receptors in the Phosphoinositide Cycle

Abstract

Abundant evidence suggests that the phosphoinositide (PI) system is a prominent and prevalent second messenger system. In addition to mediating short term changes in humoral transmission, the PI cycle may regulate long term alterations evoked by growth factors, hormones and in learning and memory, as is exemplified by long term potentiation. The PI cycle influences cellular function through the generation of diacylglycerol (DAG) and inositol trisphosphate (IP3) as well as other inositol phosphates. DAG stimulates protein kinase C (PKC), whereas the primary function of IP3 is to release calcium from intracellular stores. It is easy to conceptualize how IP3-induced release of calcium would activate short term alterations such as neuronal firing or muscle contraction. One of the challenges of PI research is to determine mechanisms whereby growth, differentiation and synaptic plasticity might be modulated by this Second messenger system. Another challenge is to explain how discrete processing of information can be handled by a single second messenger system which is responsive to so many different primary messengers. Neurotransmitters achieve their selectivity, in part, by acting at subtypes of receptors. Accordingly, one might expect heterogeneity among the various enzymes and binding proteins involved in the PI cycle (for a comprehensive review of the PI system, see Berridge 1987).