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Abstract
Melanocortin 1 receptor (MC1R) plays a key role in the physiology of the vertebrate
pigment system. Point mutations producing hyperactive or inactive receptors result
in darkening or paling effects, respectively. We report the molecular and pharmacological
characterization, as well as the tissue expression pattern, of the sea bass Mc1r.
Similar to other MC1Rs, the sea bass gene is highly polymorphic and nine DNA polymorphisms,
seven of them involving an amino acid substitution, were detected. SbMc1r is mainly
expressed in the testis, fat and liver with moderate levels in the ventral and dorsal
skin. The sea bass receptor was activated by all the melanocortins tested, with ACTH
showing the lowest efficiency. The acetylation level of the MSH isoforms seems to
be critical for the effectively of the agonist. Agouti-related protein (AGRP) drastically
inhibited the basal activity of the receptor in vitro, as an inverse agonist does,
but only in the presence of phosphodiesterase inhibitors. This observation suggests
that sbMc1r is constitutively activated and inversely regulated by AGRP, which is
expressed in the skin of different fish species.