In vivo observation of a non-noradrenergic regulation of arylalkylamine N-acetyltransferase gene expression in the rat pineal complex

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 rodent superficial pineal gland is massively innervated and contains a dense network of blood vessels into which MEL is released. However, in the deep pineal gland, being made of functional pinealocytes that express the genes coding for the MEL-synthesizing enzyme with a day/night rhythm (Ribelayga et al, 1998a;Garidou et al, 2001), MEL could as well be directly released into the cerebrospinal fluid, as has been recently demonstrated in sheep (Tricoire et al, 2002). In the course of phylogenesis, the pineal gland has undergone marked transformations (Collin, 1971;Korf et al, 1998).…”

“…Central fibers arrive and terminate mostly in the proximal part of the pineal gland. This does not exclude a physiological effect of these central inputs because 1) electrophysiological and biochemical connections occur between the pinealocytes (Reuss et al, 1984, Saez et al, 1994 and 2) the stalk and the deep part of the rodent pineal gland possess true pinealocytes that contain the enzymes of MEL synthesis (Ribelayga et al, 1998a;Garidou et al, 2001). In nonrodents, where the whole pineal gland is located close to the third ventricle, the central innervation may be denser and thereby functionally more important (see Møller, 1999 for review).…”

“…In the rat pineal gland mRNA expression, protein, and activity of AA-NAT are nearly undetectable during the day and increase markedly (between 70-and 150-fold) during the night (Borjigin et al, 1995;Klein et al, 1996;Roseboom et al, 1996;Gastel et al, 1998;Garidou et al, 2001;Fig. 5).…”

“…The pivotal role of NE in the control of rat pineal metabolic activity has been supported by several experiments: 1) intraperitoneal injections of an NAergic agonist during the day stimulate MEL synthesis with a comparable amplitude to that of the endogenous nocturnal increase (see King and Steinlechner, 1985 for review); 2) SCGx abolishes the nocturnal increase in Aanat mRNA, AA-NAT activity, and MEL synthesis (Deguchi and Axelrod, 1972b;Roseboom et al, 1996;Garidou et al, 2001); 3) electrical SCG stimulation during the day provokes an increase in MEL synthesis in the pineal gland (Bowers and Zigmond, 1980); 4) exogenous NAergic stimulation of the pineal gland in organ cultures or in perifusion (Simonneaux et al, 1989) or of pinealocytes in primary culture Simonneaux et al, 1994b) induces a large increase in AA-NAT activity and MEL release; 5) the synthetic rate and renewal of NE in the pineal gland are higher at night than during the day (Brownstein and Axelrod, 1974;Craft et al, 1984); and 6) the use of pineal microdialysis to study the in situ regulation of MEL synthesis has demonstrated the positive coupling between the nighttime release of NE and stimulation of MEL synthesis (Drijfhout et al, 1993(Drijfhout et al, , 1996c.…”

“…Importantly, the cAMPinduced activation of PKA has several effects on AA-NAT activation. First, the nocturnal increase in cAMPdependent P-CREB induces a massive (100 -150-fold in the rat) nocturnal increase in Aa-nat gene expression (Borjigin et al, 1995;Roseboom et al, 1996;Garidou et al, 2001). Translation of Aa-nat mRNA results in a large increase (70 -100-fold) in the protein level.…”