Rhythms in Second Messenger Mechanisms

Abstract

Circadian rhythmicity has been observed in several biochemical, hormonal, and physiological parameters, and evidence exists that disturbances in these rhythms are involved in disease processes such as Cushing’s syndrome, secondary hypertension, and affective disorders. A crucial step in physiological regulation and signalling is the transduction of signals from the extracellular to the intracellular space crossing the cell membrane. One of the major pathways involved in transmembraneous signalling is the combination of an extracellular receptor and an intracellular effector molecule responsible for the synthesis of an intracellular second messenger, e.g. the β-adrenoceptor—G-protein—adenylyl cyclase complex or the α-adrenoceptor—G-protein—phospholipase C system. In the case of lipid-soluble mediators such as nitric oxide, an intracellularly located effector molecule, i.e. the soluble guanylyl cyclase, may be the target protein. The present review will focus on circadian rhythms in the above-mentioned second messenger pathways involved in formation of cAMP by adenylyl cyclase, of cGMP by guanylyl cyclases, and of inositol phosphates by phospholipase C. Since the contribution of second messengers to the function of the clock itself has been discussed elsewhere (Prosser and Gillette 1991; Takahashi et al. 1993; Takahashi 1993) and is reviewed in other chapters of this handbook, this point will not be discussed here. We shall also restrict our review to data obtained in humans and in other mammalian species; results concerning unicellular organisms were subject of detailed reviews (Edmunds 1988; Edmunds et al. 1992) and are addressed in other chapters of the handbook.