Dopaminergic inhibition of tyrosinase activity in hair follicular melanocytes of the mouse.
Bromocriptine, a dopamine agonist that blocks the secretion of MSH, inhibits melanogenesis in the hair follicular melanocytes of pubertal C3H-HeAvy mice. However, since this effect cannot be explained by a reduction in circulating alpha-MSH, we have examined the possibility that dopaminergic mechanisms may have a direct inhibitory effect on these melanocytes. Bromocriptine decreased tyrosinase activity in skin explants from 30- to 35-day-old mice that were growing dark hair. This decrease in tyrosinase activity was blocked by dopamine receptor antagonists, haloperidol or spiperone. The specific D2 agonist LY 171555 also inhibited tyrosinase activity in the skin explants in a dose-related manner and the effect was blocked by sulpiride, a D2-receptor antagonist. Neither bromocriptine nor LY 171555 had any effect on tyrosinase activity in skin explants taken from adult mice that were growing yellow hair. The D1-receptor agonist SKF 38393 had no effect on tyrosinase activity in skin explants from either group of mice. The present results support the idea that dopamine D2-receptor agonists have a direct inhibitory effect upon tyrosinase activity of hair follicular melanocytes of the C3H-HeAvy mouse. However, this effect was confined to periods of dark hair growth when the melanocytes produce eumelanin. The D2 agonists were ineffective in reducing tyrosinase activity during adult life when the melanocytes produce predominantly phaeomelanin. This suggests that different control mechanisms may operate in the hair follicular melanocytes during periods of eumelanin and phaeomelanin synthesis.
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000375:Aging / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology; D004156:Catechol Oxidase / Q000378:metabolism*; D003864:Depression, Chemical; D004298:Dopamine / Q000502:physiology*; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D006197:Hair / Q000166:cytology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008544:Melanocytes / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008809:Mice, Inbred C3H; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D019257:Quinpirole; D012867:Skin / Q000201:enzymology; D013134:Spiperone / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D004873:Ergolines; D019257:Quinpirole; D001971:Bromocriptine; D013134:Spiperone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase; D006220:Haloperidol; D004298:Dopamine