Cholinergic signaling in the rat pineal gland

Abstract

1. Innervation of the mammalian pineal gland is mainly sympathetic. Pineal synthesis of melatonin and its levels in the circulation are thought to be under strict adrenergic control of serotonin N-acetyltransferase (NAT). In addition, several putative pineal neurotransmitters modulate melatonin synthesis and secretion. 2. In this review, we summarize what is currently known on the pineal cholinergic system. Cholinergic signaling in the rat pineal gland is suggested based on the localization of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), as well as muscarinic and nicotinic ACh binding sites in the gland. 3. A functional role of ACh may be regulation of pineal synaptic ribbon numbers and modulation of melatonin secretion, events possibly mediated by phosphoinositide (PI) hydrolysis and activation of protein kinase C via muscarinic ACh receptors (mAChRs). 4. We also present previously unpublished data obtained using primary cultures of rat pinealocytes in an attempt to get more direct information on the effects of cholinergic stimulus on pinealocyte melatonin secretion. These studies revealed that the cholinergic effects on melatonin release are restricted mainly to intact pineal glands since they were not readily detected in primary pinealocyte cultures.

Night/Day Changes in Pineal Expression of >600 Genes

“…Other less well studied genes in a pineal context included the receptors for prolactin, acetylcholine, GABA, glutamate, and interleukin, suggesting roles in pineal gland signaling. Acetylcholine receptor expression is consistent with anatomical evidence (5) that reveals the presence of nonsympathetic, probably parasympathetic, nerve fibers in the pineal gland of the rat and with biochemical studies that have shown the presence of both muscarinic (107) and nicotinic (108) cholinergic receptors. Furthermore, it has been shown that a cholinergic input to the rat pineal gland causes the release of glutamate, which has been reported to act via glutamate receptors on the pinealocyte membrane to inhibit melatonin synthesis (109,110).…”

Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

“…The main effect of mACh-R activation, however, probably occurs at the presynaptic level. A presynaptic effect was first postulated following the observation of an effect of ACh on the whole pineal gland but not on cultured pinealocytes (Laitinen et al, 1995). This hypothesis has now been confirmed by pineal microdialysis showing that carbachol inhibits the production of NAS and MEL via presynaptic inhibition of NE release .…”

Stimulation of a nicotinic ACh receptor causes depolarization and activation of L‐type Ca2+ channels in rat pinealocytes.

“…It has been estimated that calcium-specific currents of only 2 pA can raise levels of intracellular Ca2+ at a rate of 100 nM s-' (Neher, 1992 (Kamishima & McCarron, 1996). (Stankov et al 1993;Drijfhout et al 1996) but the precise signalling pathways remain elusive (Laitinen et al 1995). One possibility may be that the stimulation of the nAChR and the subsequent activation of the L-type Ca2+ channel stimulates release of glutamate, shown to accumulate in microvesicles of the pinealocytes (Redecker & Veh, 1994), and to inhibit melatonin secretion (Kus, Handa & McNulty, 1994).…”

“…Further evidence for a cholinergic innervation of the pineal organ has been obtained by recent immunocytochemical studies (E. Weihe, M. K.-H. Schaifer & L. E. Eiden, personal communication) using antibodies against the vesicular ACh transporter (Weihe, Tao-Cheng, Schiifer, Erickson & Eiden, 1996). Possible effects of cholinergic agonists on melatonin production and release have been repeatedly investigated (for review see Laitinen, Laitinen & Kokkola, 1995), but the data are equivocal with regard to the receptor types t To whom correspondence should be addressed. 6026 involved, their location and the functional consequences of their activation.…”