Melanocortin receptor-mediated mobilization of intracellular free calcium in HEK293 cells

• Published in: Physiological genomics Vol. 5; no. 1; pp. 11 - 19
• Main Authors: MOUNTJOY, KATHLEEN G, KONG, PHILIP L, TAYLOR, JOHN A, WILLARD, DERRIL H, WILKISON, WILLIAM O
• Format: Journal Article
• Language: English
• Published: United States Am Physiological Soc 07.02.2001
• Subjects: Agouti Signaling Protein; alpha-MSH - analogs & derivatives; alpha-MSH - pharmacology; Animals; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Carbachol - pharmacology; Cell Line; Cholera Toxin - pharmacology; Dose-Response Relationship, Drug; Humans; Inositol Phosphates - metabolism; Intercellular Signaling Peptides and Proteins; Ionomycin - pharmacology; Manganese - pharmacology; Mice; Peptide Fragments - pharmacology; Proteins - pharmacology; Receptor, Melanocortin, Type 3; Receptors, Corticotropin - physiology; Receptors, Melanocortin; Signal Transduction - drug effects; Thapsigargin - pharmacology
• ISSN: 1094-8341; 1531-2267
• DOI: 10.1152/physiolgenomics.2001.5.1.11

1 Research Centre for Developmental Medicine and Biology, Department of Paediatrics 2 School of Biological Sciences, University of Auckland, Auckland 1, New Zealand 3 Glaxo Wellcome Research Institute, Research Triangle Park, North Carolina 27709 Mouse melanocortin receptors, MC1-R, MC3-R, MC4-R, and MC5-R, when expressed in HEK293 cells and stimulated with either -melanocyte-stimulating hormone ( -MSH) or desacetyl- -MSH, mediate increases in intracellular free calcium concentration ([Ca 2+ ] i ) with EC 50 values between 0.3 and 4.3 nM. The increase in [Ca 2+ ] i is cholera toxin sensitive and pertussis toxin insensitive. The mechanism involves calcium mobilization from intracellular stores without a transient rise in inositol trisphosphate. Mouse agouti protein (55 nM) is a competitive antagonist of -MSH (6-fold) and desacetyl- -MSH (8-fold), coupling the mMC1-R to increased [Ca 2+ ] i . Agouti protein (55 nM) significantly increased the EC 50 for -MSH (3-fold), and 550 nM agouti protein significantly increased the EC 50 for desacetyl- -MSH (4-fold), coupling the mMC4-R to a rise in [Ca 2+ ] i . However, agouti protein antagonism of the MC4-R may not be competitive since there was a trend for the maximum response to also increase. There was no significant antagonism of the MC3-R and MC5-R by agouti protein (55 nM). Understanding the physiological relevance of the transduction of a calcium signal by melanocortin peptides may be important for future development of therapeutic targeting of the melanocortin receptors. agouti; desacetyl- -melanocyte-stimulating hormone; -melanocyte-stimulating hormone