Norepinephrine Release in the Rat Pineal Gland: The Input from the Biological Clock Measured by In Vivo Microdialysis

Abstract

The sympathetic innervation of the rat pineal gland was investigated, measuring the norepinephrine (NE) release by on-line in vivo microdialysis. NE was assayed using an HPLC method with precolumn derivatization and fluorescence detection. Its high sensitivity and reliability made it very suitable to monitor the low levels of NE in the dialysates (12.5 fmol during nighttime, 3 fmol during daytime). To increase NE levels, the monoamine reuptake inhibitor cocaine was added to Ringer's solution at concentrations of 10-6 and 10~M. This resulted in increases of neurotransmitter output of 167 and 219%, respectively, but did not change the qualitative and/or quantitative outcome of other experiments. Perfusion with 10 6 M tetrodotoxin for 1 h resulted in a decrease of the NE release by >80%, whereas perfusion with the cn 2-receptor antagonist yohimbine caused a twofold in-

Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

“…This diminution results from various cellular and molecular mechanisms mainly initiated by the termination of NE release (Drijfhout et al, 1996d). Cessation of NE release is thought to be SCN clock-driven but also depends on local presynaptic inhibition via ␣ 2 -AR (Pelayo et al, 1977;Simonneaux et al, 1994a).…”

Rhythmic Expression of Adenylyl Cyclase VI Contributes to the Differential Regulation of Serotonin N-Acetyltransferase by Bradykinin in Rat Pineal Glands

“…There is no doubt that termination of melatonin synthesis is mainly initiated by the termination of norepinephrine release (46). Other mechanisms have been proposed, such as rapid proteasomal proteolysis of AANAT (47) and inhibition of ␤-adrenergic signaling by metabotropic glutamate receptors through the inhibitory guanine nucleotide-binding protein (Gi) (48).…”

Neuropeptide Y as a presynaptic modulator of norepinephrine release from the sympathetic nerve fibers in the pig pineal gland

“…The sympathetic input is crucial for the precise regulation of rhythmic melatonin secretion in the mammalian pineal gland, as it constitutes the last step of multisynaptic pathway connecting this organ with the suprachiasmatic nucleus and the retina (Drijfhout et al 1996a, Larsen et al 1998. In addition to the sympathetic innervation, the pineal gland receives also nerve fibers from other peripheral ganglia and from the brain (Mzller et al 1996, 1999, Matsushima et al 1999.…”

“…Among neurotransmitters occurring in the pineal nerve endings, norepinephrine (NE) and neuropeptide Y (NPY) are present in the highest amounts (Williams et al 1989, Møller 1990, Møller et al 1990, 1996, Zhang et al 1991, Cozzi et al 1992, Olcese 1994, Reuss and Olcese 1995, Drijfhout et al 1996a, Mikkelsen and Møller 1999, Simonneaux and Ribelayga 2003. Both substances co-exist in the sympathetic nerve fibers, but NPY also occurs in a small population of non-sympathetic fibers, probably of the central origin , Zhang et al 1991, Møller et al, 1996, Møller 1999.…”