The rainbow trout (Oncorhynchus mykiss) is one of the most widely used fish species in aquaculture and physiological research. In the present paper, we report the first cloning, 3D (three-dimensional) modelling, pharmacological characterization and tissue distribution of two melanocortin (MC) receptors in rainbow trout. Phylogenetic analysis indicates that these receptors are orthologues of the human MC4 and MC5 receptors. We created 3D molecular models of these rainbow trout receptors and their human counterparts. These models suggest greater divergence between the two human receptors than between their rainbow trout counterparts. The pharmacological analyses demonstrated that ACTH (adrenocorticotropic hormone) had surprisingly high affinity for the rainbow trout MC4 and MC5 receptors, whereas α-, β- and γ-MSH (melanocyte-stimulating hormone) had lower affinity. In second-messenger studies, the cyclic MSH analogues MTII and SHU9119 acted as potent agonist and antagonist respectively at the rainbow trout MC4 receptor, indicating that these ligands are suitable for physiological studies in rainbow trout. Interestingly, we found that the rainbow trout MC4 receptor has a natural high-affinity binding site for zinc ions (0.5 µM) indicating that zinc may play an evolutionary conserved role at this receptor. Reverse transcription PCR indicates that the rainbow trout receptors are expressed both in peripheral tissues and in the central nervous system, including the telencephalon, optic tectum and hypothalamus. Overall, this analysis indicates that the rainbow trout MC4 and MC5 receptors have more in common than their mammalian counterparts, which may suggest that these two receptors have a closer evolutionary relationship than the other MC receptor subtypes.
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Research Article|
June 01 2004
Cloning, tissue distribution, pharmacology and three-dimensional modelling of melanocortin receptors 4 and 5 in rainbow trout suggest close evolutionary relationship of these subtypes
Tatjana HAITINA;
Tatjana HAITINA
*Department of Neuroscience, Unit of Pharmacology, Uppsala University, BMC, Uppsala SE75124, Sweden
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Janis KLOVINS;
Janis KLOVINS
*Department of Neuroscience, Unit of Pharmacology, Uppsala University, BMC, Uppsala SE75124, Sweden
†Biomedical Research and Study Centre, University of Latvia, Riga LV1069, Latvia
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Jan ANDERSSON;
Jan ANDERSSON
*Department of Neuroscience, Unit of Pharmacology, Uppsala University, BMC, Uppsala SE75124, Sweden
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Robert FREDRIKSSON;
Robert FREDRIKSSON
*Department of Neuroscience, Unit of Pharmacology, Uppsala University, BMC, Uppsala SE75124, Sweden
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Malin C. LAGERSTRÖM;
Malin C. LAGERSTRÖM
*Department of Neuroscience, Unit of Pharmacology, Uppsala University, BMC, Uppsala SE75124, Sweden
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Dan LARHAMMAR;
Dan LARHAMMAR
*Department of Neuroscience, Unit of Pharmacology, Uppsala University, BMC, Uppsala SE75124, Sweden
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Earl T. LARSON;
Earl T. LARSON
‡Departments of Biology and Psychology, Northeastern University, Boston, MA 02115, U.S.A.
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Helgi B. SCHIÖTH
Helgi B. SCHIÖTH
1
*Department of Neuroscience, Unit of Pharmacology, Uppsala University, BMC, Uppsala SE75124, Sweden
1To whom correspondence should be addressed (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
December 15 2003
Revision Received:
February 09 2004
Accepted:
February 13 2004
Accepted Manuscript online:
February 13 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 380 (2): 475–486.
Article history
Received:
December 15 2003
Revision Received:
February 09 2004
Accepted:
February 13 2004
Accepted Manuscript online:
February 13 2004
Citation
Tatjana HAITINA, Janis KLOVINS, Jan ANDERSSON, Robert FREDRIKSSON, Malin C. LAGERSTRÖM, Dan LARHAMMAR, Earl T. LARSON, Helgi B. SCHIÖTH; Cloning, tissue distribution, pharmacology and three-dimensional modelling of melanocortin receptors 4 and 5 in rainbow trout suggest close evolutionary relationship of these subtypes. Biochem J 1 June 2004; 380 (2): 475–486. doi: https://doi.org/10.1042/bj20031934
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