Rodent lymphocytes express functionally active glutamate receptors.
RT-PCR demonstrated that ionotropic (iGluR NR1) and metabotropic (mGluR Group III) glutamate receptors are expressed in rodent lymphocytes. Flow cytometry showed that activation of iGluR NR1 by N-methyl-D-aspartate (NMDA) increased intracellular free calcium and reactive oxygen species (ROS) levels and activated caspase-3. The latter effect was attenuated by the NMDA antagonist, 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), by the antioxidant N-acetylcysteine and by cyclosporin A. Treatment with L-2-amino-4-phosphonobutyric acid (L-AP4), an mGluR Group III agonist, increased lymphocyte ROS levels but to a lower extent than did NMDA. Activation of lymphocytes with both NMDA and L-AP4 caused a synergistic increase in ROS levels and induced necrotic cellular death without elevating the caspase-3 activation observed in the presence of NMDA alone. These results show that lymphocyte iGluR NR1 and mGluR Group III receptors may be involved in controlling rodent lymphocyte functions and longevity as they regulate events in cell proliferation, maturation, and death.
Department of Biochemistry, Center for Molecular Medicine and International Biotechnological Center, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia.
Alexander A
AA
Boldyrev
Vasily I
VI
Kazey
Toomas A
TA
Leinsoo
Anna P
AP
Mashkina
Olga V
OV
Tyulina
Peter
P
Johnson
Jelena O
JO
Tuneva
Sridar
S
Chittur
David O
DO
Carpenter
D000613:Aminobutyrates / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000494:pharmacology; D004789:Enzyme Activation; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016202:N-Methylaspartate / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
D000613:Aminobutyrates; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C409466:NR1 NMDA receptor; D017382:Reactive Oxygen Species; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C012729:2-amino-4-phosphonobutyric acid; D002118:Calcium