Human melanocortin 1 receptor variants, receptor function and melanocyte response to UV radiation
M. Cathy Scott1,
Kazumasa Wakamatsu2,
Shosuke Ito2,
Ana Luisa Kadekaro1,
Nobuhiko Kobayashi3,
Joanna Groden4,
Renny Kavanagh1,
Takako Takakuwa5,
Victoria Virador6,
Vincent J. Hearing6 and
Zalfa A. Abdel-Malek1,*
1 Department of Dermatology, University of Cincinnati College of Medicine, PO
Box 670592, Cincinnati, Ohio 45267-0592, USA
2 Fujita Health University School of Health Sciences, Toyoake, Aichi 470-1192,
Japan
3 Department of Dermatology, Nara Medical University, Kashihara, Nara 634-8522,
Japan
4 Department of Molecular Genetics, Biochemistry and Microbiology, University of
Cincinnati College of Medicine, PO Box 670524, Cincinnati, Ohio 45267-0524,
USA
5 POLA Laboratories, 560 Kashio-cho, Totsuka-ku, Yokohama 244-0812, Japan
6 Laboratory of Cell Biology, National Cancer Institute, National Institutes of
Health, 9000 Rockville Pike, Bethesda, MD 20892, USA
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Fig. 1. Dose-responses of various melanocyte cultures to  -MSH. The responses
of NHM 753-c, 830-c, 849-b and 755-c, homozygous or compound heterozygous for
MC1R variants, and NHM 747-c, 729-c and 751-b, homozygous for the
consensus MC1R were compared. The response of NHM 765-c, heterozygous
for Val92Met substitution, is also presented, since it is comparable to NHM
753-c and 830-c in the ratio of eumelanin to pheomelanin. The responses to
-MSH were tested as described in the Materials and Methods. The effects
of increasing doses of -MSH on cAMP formation, tyrosinase activity and
cell proliferation are presented in A, B and C, respectively. Basal levels of
cAMP (Pmole/106 cells) in the cultures tested were as follows:
753-c=2.176±0.134; 830-c=1.451; 849-b=1.172±0.0219;
755-c=2.193±0.206; 765-c=1.675±0.137; 747-c=1.074±0.098;
729-b=2.007±0.128; 751-b=0.84±0.103. In A and B, each value
represents the mean percent of control of six determinations±s.e. In C,
each value is the mean percent of control of three
determinations±s.e.
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Fig. 2. Cytotoxic effects of UVBR on melanocytes with different MC1R genotypes. We
compared the response to UVBR of NHM 753-c, 830-c and 849-b homozygous or
heterozygous for loss-of-function mutations in MC1R to that of NHM
765-c and NHM 755-c, heterozygous or homozygous for Val92Met substitution,
respectively. All melanocyte cultures were irradiated a single time with UVBR
and cell number and viability were determined on days 2 and 4 after
irradiation, as described in Materials and Methods. Each value represents the
mean percent cell death of three determinations±s.e.
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© The Company of Biologists Ltd 2002
