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

In adult rat pinealocytes, acetylcholine activates nicotinic receptors whos e stimulation causes a depolarization of the cells, opening of voltage-gate d cation channels of the L-type and subsequent increase in the intracellula r calcium ion concentration. These events trigger a release of glutamate th at, by its action on metabotropic glutamate type 3 receptors, activates an inhibitory cyclic AMP cascade and suppresses norepinephrine-induced melaton in biosynthesis. The nicotinic response is fully developed in the third pos tnatal week. Prior to this timepoint, rat pinealocytes possess functional m uscarinic receptors whose activation causes a rise in the intracellular cal cium ion concentration through a calcium release from thapsigargin sensitiv e intracellular calcium stores and an opening of store-operated calcium cha nnels. This cascade may influence tissue differentiation and maturation of the melatonin pathway. The demonstration of functional cholinoreceptors and the ontogenetic switch from muscarinic to nicotinic signalling in rat pine alocytes supports the concept that pineal functions in mammals are influenc ed by neuronal inputs other than the sympathetic innervation which serves a s the major regulatory system. (C) Inra/Elsevier, Paris.