Expression of functional mGlu5 metabotropic glutamate receptors in human melanocytes

Cultured human melanocytes express mGlu5 metabotropic glutamate (mGlu) rece ptors, as shown by RT-PCR, immunocytochemistry, Western blot analysis, and measurement of agonist-stimulated polyphosphoinositide hydrolysis. The mGlu 5 receptor agonists (S)-3,5-dihydroxyphenylglycine and quisqualate increase d [H-3-methyl]thymidine incorporation and melanocyte proliferation in subco nfluent cultures, but impaired cell viability in confluent cultures. Both e ffects were prevented by 2-methyl-6-(2-phenyl-1-ethynyl)-pyridine, a potent and highly selective mGlu5 receptor antagonist. Agonists of other mGlu rec eptor subtypes (such as the mGlu2/3 receptor agonist, 2S,2'R,3'R-2-2',3'-di carboxycyclopropylglycine, or the mGlu4/6/7/8 receptor agonist, L-2-amino-4 -phosphonobutanoate) or selective agonists of ionotropic glutamate receptor s (N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazoleppropion ate, and kainate) did not affect melanocyte proliferation or viability. The presence of a receptor for glutamate, the major excitatory neurotransmitte r, in human melanocytes is intriguing. mGlu5 receptors may be involved in t he control of melanocyte proliferation (and perhaps in other functions), bu t harbor a potential toxicity and may therefore contribute to cell damage u nder pathological conditions. J. Cell. Physiol. 183:364-372, 2000. (C) 2000 Wiley-Liss, Inc.