Expression of functional mGlu5 metabotropic glutamate receptors in human melanocytes.
Cultured human melanocytes express mGlu5 metabotropic glutamate (mGlu) receptors, as shown by RT-PCR, immunocytochemistry, Western blot analysis, and measurement of agonist-stimulated polyphosphoinositide hydrolysis. The mGlu5 receptor agonists (S)-3, 5-dihydroxyphenylglycine and quisqualate increased [(3)H-methyl]thymidine incorporation and melanocyte proliferation in subconfluent cultures, but impaired cell viability in confluent cultures. Both effects were prevented by 2-methyl-6-(2-phenyl-1-ethynyl)-pyridine, a potent and highly selective mGlu5 receptor antagonist. Agonists of other mGlu receptor subtypes (such as the mGlu2/3 receptor agonist, 2S,2'R,3'R-2-2', 3'-dicarboxycyclopropylglycine, or the mGlu4/6/7/8 receptor agonist, L-2-amino-4-phosphonobutanoate) or selective agonists of ionotropic glutamate receptors (N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, and kainate) did not affect melanocyte proliferation or viability. The presence of a receptor for glutamate, the major excitatory neurotransmitter, in human melanocytes is intriguing. mGlu5 receptors may be involved in the control of melanocyte proliferation (and perhaps in other functions), but harbor a potential toxicity and may therefore contribute to cell damage under pathological conditions.
Frati
C
C
Department of Dermatology, Ospedale di Frosinone, Frosinone, Italy.
Marchese
C
C
Fisichella
G
G
Copani
A
A
Nasca
M R
MR
Storto
M
M
Nicoletti
F
F
D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008297:Male; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010859:Pigmentation Disorders / Q000139:chemically induced; D016318:Quisqualic Acid / Q000494:pharmacology; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology; D012867:Skin / Q000166:cytology; D012970:Sodium Glutamate / Q000494:pharmacology; D014020:Tissue Extracts / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018129:Phosphatidylinositol Phosphates; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D014020:Tissue Extracts; C079215:3,5-dihydroxyphenylglycine; D016318:Quisqualic Acid; D004247:DNA; D005998:Glycine; D012970:Sodium Glutamate