Wj. Drijfhout et al., PARASYMPATHETIC INHIBITION OF PINEAL INDOLE METABOLISM BY PREJUNCTIONAL MODULATION OF NORADRENALINE RELEASE, European journal of pharmacology, 308(2), 1996, pp. 117-124
The role of the parasympathetic nervous system in rat pineal indole me
tabolism was investigated by transpineal in vivo microdialysis. On-lin
e coupling to a high performance liquid chromatography system with flu
orescence detection (HPLC-FD) allowed simultaneous analysis of three m
ajor indolic compounds from the pineal, i.e. serotonin, N-acetylseroto
nin and melatonin. Infusion of the muscarinic receptor agonists, carba
chol and oxotremorine, during the dark period resulted in a marked dec
rease of melatonin release. This effect was suggested to be mediated b
y a decrease in N-acetyltransferase activity, since a similar decrease
was seen in N-acetylserotonin release, while serotonin levels increas
ed simultaneously. Nicotine did show a very slight effect on the three
indoles under these circumstances. Neostigmine failed to influence pi
neal indole metabolism, indicating that the endogenous tonus of acetyl
choline release is either absent or extremely low in the middle of the
dark period. The involvement of sympathetic innervation in the muscar
inic effects was investigated by measurement of noradrenaline release
from the pineal by sensitive off-line HPLC-FD analysis of noradrenalin
e in the dialysates. Carbachol markedly decreased the noradrenaline in
put during the infusion. Noradrenaline release returned to baseline va
lues immediately after infusion with carbachol. These data suggest tha
t the in vivo inhibitory effect of muscarinic receptor agonists on pin
eal melatonin production is mediated by presynaptic muscarinic recepto
rs, located on the sympathetic nerve endings. This prejunctional inhib
ition of noradrenaline release causes a reduced induction of N-acetylt
ransferase activity, resulting in decreased melatonin release.