Diurnal changes in pineal extracellular indoles of freely moving rats

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 in vitro release of 5-HT from stimulated rat pinealocytes depends on the metabolic orientation of 5-HT that depends on the level of AA-NAT activity: with moderate ␤ 1 -AR stimulation, the synthesis and release of both 5-HT and MEL are increased; following strong ␤ 1 -AR stimulation, the intracellular levels and release of 5-HT are markedly decreased while MEL synthesis and release are maximal (Miguez et al, 1997). These in vitro results are in agreement with the observations found using pineal microdialysis (Azekawa et al, 1991;Sun et al, 2002), namely that extracellular 5-HT levels are high during the day, further increased at the beginning of the night, and then markedly decreased during the night because of a major mobilization of 5-HT for MEL synthesis. This triphasic rhythm in 5-HT release is circadian and depends on the NAergic input (Sun et al, 2002).…”

“…Consequently, any variation in nighttime HIOMT activity should modulate the rate of MEL synthesis (the amplitude of the nocturnal MEL peak). This hypothesis is strengthened by the following observations: 1) an excess of NAS is released in the extracellular compartment at night (Azekawa et al, 1991;Sun et al, 2002) or following NAergic stimulation (Berg and Klein, 1971;Miguez et al, 1997); 2) the NAS concentration can be up to 2-fold greater than that of MEL in the rat and the Siberian hamster (Steinlechner et al, 1995); 3) when Siberian hamsters are transferred from LP to SP, the increase in the amplitude of the nocturnal MEL peak is not related to a similar increase in nocturnal AA-NAT activity, but in contrast to a decrease (Illnerova et al, 1984;Ribelayga et al, 2000); and 4) in the Siberian hamster, parallelism between daily variations of NAS and MEL is not always observed throughout along the year (especially in September; Steinlechner et al, 1995).…”

“…It is noteworthy, however, that there is a high level of NAS release in vitro from NEstimulated cultured pinealocytes (Miguez et al, 1997) and in vivo in the extracellular medium of microdialyzed nocturnal pineal glands (Azekawa et al, 1991;Sun et al, 2002). These observations suggest that part of the NAS synthesized by AA-NAT is not used by HIOMT to produce MEL, and thus in conditions of marked pineal stimulation HIOMT, rather than AA-NAT, limits MEL synthesis.…”

“…Furthermore, using pineal microdialysis, it has been shown that 5-HT is released in the pineal extracellular medium during the day with a significant increase at the beginning of the night followed by a marked decrease later in the night (Azekawa et al, 1991;Sun et al, 2002). These observations, suggesting that pineal 5-HT may display auto/paracrine effects on pineal metabolism, have triggered several studies to elucidate the mechanisms regulating 5-HT release and the role of 5-HT in the rat pineal gland (Sugden, 1990a;Miguez et al, 1997).…”

“…In the rat pineal gland extracellular 5-HT concentrations increase at the beginning of the night (Azekawa et al, 1991;Sun et al, 2002) when NAergic stimulation is probably still moderated. This transient increase could help to increase the nocturnal stimulation of MEL synthesis.…”