1. Innervation of the mammalian pineal gland is mainly sympathetic, Pi
neal synthesis of melatonin and its levels in the circulation are thou
ght to be under strict adrenergic control of serotonin N-acetyltransfe
rase (NAT). In addition, several putative pineal neurotransmitters mod
ulate melatonin synthesis and secretion. 2. In this review, we summari
ze what is currently known on the pineal cholinergic system, Cholinerg
ic signaling in the rat pineal gland is suggested based on the localiz
ation of choline acetyltransferase (ChAT) and acetylcholinesterase (AC
hE), as well as muscarinic and nicotinic ACh binding sites in the glan
d. 3. A functional role of ACh may be regulation of pineal synaptic ri
bbon numbers and modulation of melatonin secretion, events possibly me
diated by phosphoinositide (PI) hydrolysis and activation of protein k
inase C via muscarinic ACh receptors (mAChRs). 4. We also present prev
iously unpublished data obtained using primary cultures of rat pinealo
cytes in an attempt to get more direct information on the effects of c
holinergic stimulus on pinealocyte melatonin secretion, These studies
revealed that the cholinergic effects on melatonin release are restric
ted mainly to intact pineal glands since they were not readily detecte
d in primary pinealocyte cultures.