Pineal Regulation - Transsynaptic and Intracellular Mechanisms

Klein, D C.

Abstract

The goal of this project is to discover the molecular basis of neurochemical transduction mechanisms, using the pineal gland as a model. This program has yielded new information on how Alpha 1-adrenoceptors participate with Beta 1-adrenoceptors in the synergistic regulation of cAMP and cGMP. Alpha 1-Adrenoceptors appear to open a ligand dependent calcium channel, which leads to a 5-fold increase in the apparent intracellular concentration of calcium. In addition Alpha 1-adrenoceptors alter aphospholipid metabolism, by stimulating the activity of both phospholipase A2 and phospholipase C. The combined effects of the increase in calcium and phospholipase C activity potentiates the Beta-adrenergic stimulation of adenylate cyclase; the combined effects of the increase in calcium and of phospholipase A lead to an increase in the Beta-adrenergic stimulation of cGMP. Advances have been made in the purification of pineal N-acetyltransferase and hydroxyindole-O-methyltransferase, in the preparations of antisera against hydroxyindole-O-methyltransferase, preparation of bovine pineal cDNA libraries, cloning the S-antigen from a bovine retina cDNA library. Pineal processes have been described in a species of hamster and preliminary evidence of such processes in the monkey have been obtained.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
• Type: Intramural Research (Z01)
• Project #: 1Z01HD000095-10
• Application #: 3965728
• Support Year: 10
• Fiscal Year: 1986

Institution

• Name: U.S. National Inst/Child Hlth/Human Dev
• Country: United States

Publications

Klein, David C; Bailey, Michael J; Carter, David A et al. (2010) Pineal function: impact of microarray analysis. Mol Cell Endocrinol 314:170-83

Kim, Jong-So; Coon, Steven L; Weller, Joan L et al. (2009) Muscleblind-like 2: circadian expression in the mammalian pineal gland is controlled by an adrenergic-cAMP mechanism. J Neurochem 110:756-64

Ganguly, Surajit; Grodzki, Cristina; Sugden, David et al. (2007) Neural adrenergic/cyclic AMP regulation of the immunoglobulin E receptor alpha-subunit expression in the mammalian pinealocyte: a neuroendocrine/immune response link? J Biol Chem 282:32758-64

Moller, Morten; Rath, Martin F; Klein, David C (2006) The perivascular phagocyte of the mouse pineal gland: an antigen-presenting cell. Chronobiol Int 23:393-401

Kim, Jong-So; Coon, Steven L; Blackshaw, Seth et al. (2005) Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily rhythm in pineal expression. J Biol Chem 280:677-84

Iuvone, P Michael; Tosini, Gianluca; Pozdeyev, Nikita et al. (2005) Circadian clocks, clock networks, arylalkylamine N-acetyltransferase, and melatonin in the retina. Prog Retin Eye Res 24:433-56

Gaildrat, Pascaline; Moller, Morten; Mukda, Sujira et al. (2005) A novel pineal-specific product of the oligopeptide transporter PepT1 gene: circadian expression mediated by cAMP activation of an intronic promoter. J Biol Chem 280:16851-60

Nguyen, Andrew D; Pan, Chi-Jiunn; Shieh, Jeng-Jer et al. (2005) Increased cellular cholesterol efflux in glycogen storage disease type Ia mice: a potential mechanism that protects against premature atherosclerosis. FEBS Lett 579:4713-8

Ganguly, Surajit; Weller, Joan L; Ho, Anthony et al. (2005) Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. Proc Natl Acad Sci U S A 102:1222-7

Zheng, Weiping; Schwarzer, Dirk; Lebeau, Aaron et al. (2005) Cellular stability of serotonin N-acetyltransferase conferred by phosphonodifluoromethylene alanine (Pfa) substitution for Ser-205. J Biol Chem 280:10462-7