Molecular and pharmacological characterization of the melanocortin type 1 receptor in the sea bass

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 t...

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Bibliographic Details
Published in:General and comparative endocrinology 2010-01, Vol.165 (1), p.163-169
Main Authors: Sánchez, E, Rubio, V.C, Cerdá-Reverter, J.M
Format: Article
Language:English
Subjects:
Agouti-related protein (AGRP)
Agouti-Related Protein - pharmacology
Amino Acid Sequence
Animals
Bass - genetics
Bass - metabolism
Blotting, Southern
Cell Line
Constitutive activity
Dicentrarchus labrax
Endocrinology & Metabolism
Enzyme Activation - drug effects
Fish
Humans
IBMX
Inverse agonism
Liver - metabolism
Male
Marine
Melanocortin receptor 1 (MC1R)
Molecular Sequence Data
Phosphodiesterase inhibitor
Phosphodiesterase Inhibitors - pharmacology
Receptor, Melanocortin, Type 1 - chemistry
Receptor, Melanocortin, Type 1 - genetics
Receptor, Melanocortin, Type 1 - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
Testis - metabolism
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Summary: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.
ISSN:0016-6480
1095-6840
DOI:10.1016/j.ygcen.2009.06.008