Cholinergic signal transduction cascades in rat pinealocytes: functional and ontogenetic aspects

In adult rat pinealocytes, acetylcholine activates nicotinic receptors whose stimulation causes a depolarization of the cells, opening of voltage-gated cation channels of the L-type and sub- sequent increase in the intracellular calcium ion concentration. These events trigger a release of glu- tamate that, by its action on metabotropic glutamate type 3 receptors, activates an inhibitory cyclic AMP cascade and suppresses norepinephrine-induced melatonin biosynthesis. The nicotinic res- ponse is fully developed in the third postnatal week. Prior to this timepoint, rat pinealocytes possess functional muscarinic receptors whose activation causes a rise in the intracellular calcium ion concen- tration through a calcium release from thapsigargin-sensitive intracellular calcium stores and an opening of store-operated calcium channels. This cascade may influence tissue differentiation and matu- ration of the melatonin pathway. The demonstration of functional cholinoreceptors and the ontoge- netic switch from muscarinic to nicotinic signalling in rat pinealocytes supports the concept that pineal functions in mammals are influenced by neuronal inputs other than the sympathetic innerva- tion which serves as the major regulatory system. © Inra/Elsevier, Paris