1. The effect of L-glutamate (GIu) on human lymphocyte function was studied
by measuring anti-CD3 monoclonal antibody (mAb) or phytohaemagglutinin (PH
A)-induced intracellular Ca2+ ([Ca2+](i)) rise (Fura-2 method), and cell pr
oliferation (MTT assay).
2 Glu (0.001-100 muM) did not modify basal lymphocyte [Ca2+]i, but signific
antly potentiated the effects of anti-CD3 mAb or PHA. Maximal [Ca2+](i) ris
es over resting cells were: 165 +/-8 and 247 +/- 10 nM at 3.0 x 10(-2) mg m
l(-1) anti-CD3 mAb; 201 +/-4 and 266 +/-9 nM at 5.0 x 10(-2) mg ml(-1) PHA,
in the absence or presence of 1 muM GIu, respectively.
3 The Glu effect showed a bell-shape concentration-dependent relationship,
with a maximum (+90 +/-3% for anti-CD3 mAb and +57 +/-2% for PHA over Gill-
untreated cells) at 1 muM.
4 Non-NMDA receptor agonists (1 muM) showed a greater efficacy (+76 +/-2% f
or (S)-AMPA; +7 +/-4% for KA), if compared to NMDA (+46 +/-2%), or Glu itse
lf.
5 Ionotropic Glu receptor antagonists completely inhibited the effects of t
he corresponding specific receptor agonists (1 muM). The IC50 values calcul
ated were: 0.9 muM for D-APS: 0.6 muM for (+)-MK801; 0.3 muM for NBQX. Both
NBQX and KYNA were able to abolish GI; effect. The IC(50)s calculated were
: 3.4 muM for NBQX; 0.4 muM for KYNA.
6 GIu (0.1-1 mM) did not change the resting cell proliferation, whereas GIu
(I mM) significant inhibited (-27 +/-4%) PHA (1.0 x 10(-2) mg ml(-1))-indu
ced lymphocyte proliferation at 72 h.
7 In conclusion, human lymphocytes express ionotropic GIu receptors functio
nally operating as modulators of cell activation.