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Glutamic Acid – Amino Acid, Neurotransmitter, and Drug – Is Responsible for Protein Synthesis Rhythm in Hepatocyte Populations in vitro and in vivo

V. Y. Brodsky1*, L. A. Malchenko1, D. S. Konchenko2, N. D. Zvezdina2, and T. K. Dubovaya2

1Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 117808 Moscow, Russia; E-mail: brodsky.idb@bk.ru

2Pirogov Russian State Medical University, 117513 Moscow, Russia

* To whom correspondence should be addressed.

Received April 21, 2016
Primary cultures of rat hepatocytes were studied in serum-free media. Ultradian protein synthesis rhythm was used as a marker of cell synchronization in the population. Addition of glutamic acid (0.2 mg/ml) to the medium of nonsynchronous sparse cultures resulted in detection of a common protein synthesis rhythm, hence in synchronization of the cells. The antagonist of glutamic acid metabotropic receptors MCPG (0.01 mg/ml) added together with glutamic acid abolished the synchronization effect; in sparse cultures, no rhythm was detected. Feeding rats with glutamic acid (30 mg with food) resulted in protein synthesis rhythm in sparse cultures obtained from the rats. After feeding without glutamic acid, linear kinetics of protein synthesis was revealed. Thus, glutamic acid, a component of blood as a non-neural transmitter, can synchronize the activity of hepatocytes and can form common rhythm of protein synthesis in vitro and in vivo. This effect is realized via receptors. Mechanisms of cell–cell communication are discussed on analyzing effects of non-neural functions of neurotransmitters. Glutamic acid is used clinically in humans. Hence, a previously unknown function of this drug is revealed.
KEY WORDS: glutamic acid, kinetics of protein synthesis, direct cell–cell communication, ultradian rhythms, non-neural function of neurotransmitters, hepatocytes

DOI: 10.1134/S0006297916080101