PARASYMPATHETIC INHIBITION OF PINEAL INDOLE METABOLISM BY PREJUNCTIONAL MODULATION OF NORADRENALINE RELEASE

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.