The Melanocortin Receptors (The Receptors) by Roger D. Cone

By Roger D. Cone

Content material: pt. 1. ancient views -- Proopiomelanocortin and the melanocortin peptides -- Melanocortins and pigmentation -- Melanocortins and adrenocortical functionality -- results of melanocortins within the apprehensive process -- Peripheral results of melanocortins -- pt. 2. Characterization of the melanocortin receptors -- Melanocrotin receptor expression and serve as within the worried method -- Cloning of the melanocortin receptors -- pt. three. Biochemical mechanism of receptor motion -- The molecular pharmacology of alpha-melanocyte stimulating hormone: structure-activity relationships for melanotropins at melanocortin receptors -- In vitro mutagenesis stories of melanocortin receptor coupling and ligand binding -- pt. four. Receptor functionality -- the melanocortin-1 receptor -- The human melanocortin-1 receptor -- The melanocortin-2 receptor in general adrenocrotical funciton and familial adrenocrorticotropic hormone resistance -- The melanocortin-3 receptor -- The melanocortin-4 receptor -- The melanocortin-5 receptor -- pt. five. Receptor law -- rules of the melanocortin receptors via Agouti -- Melanocrotins and cancer -- rules of the mouse and human melanocortin-1 receptor -- pt. 6. destiny vistas -- destiny vistas

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The Melanocortin Receptors (The Receptors)

Content material: pt. 1. old views -- Proopiomelanocortin and the melanocortin peptides -- Melanocortins and pigmentation -- Melanocortins and adrenocortical functionality -- results of melanocortins within the anxious method -- Peripheral results of melanocortins -- pt. 2. Characterization of the melanocortin receptors -- Melanocrotin receptor expression and serve as within the anxious method -- Cloning of the melanocortin receptors -- pt.

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In another approach, radioiodinated _-MSH containing a biotinyl group at the N-terminus and a photoactivatable group on the Lys11 side chain, into which a disulfide group had been incorporated, was crosslinked with the MC1-R of B16 mouse melanoma cells. The cells were homogenized and the receptor solubilized in Triton X-100 and bound to magnetic beads containing streptavidin (244). A doublet-band of labeled receptor of approx 43–46 kDa was identified and partially purified. Using Cloudman S91 cells, crosslinking of external and internalized MC1 receptor showed identical molecular weights of 50–53 kDa (245).

Much higher specific radioactivities were obtained with 125I incorporated into Tyr2 of _-MSH, Tyr5 of `-MSH or Tyr23 of ACTH[1–24], yielding tracer molecules of >2000 Ci/mmol (8). However, the biologic activity of monoiodinated _-MSH (or `-MSH) could only be retained by using a peptide whose Met4 was either replaced by Nle4 or which was carefully reduced after partial oxidation during the iodination procedure (170). Radioiodination of Tyr2 of ACTH[1– 24] or 1–39 generally led to inactive radioligands; inactivation could be 14 POMC and Melanocortin Peptides 35 avoided (171) by radioiodination of Tyr23 of a precursor whose Tyr2 was replaced by Phe2 and its Met4 by Nle4 (see above).

Analogs for Therapeutic Application Whereas _-MSH has not yet been introduced to the clinic, ACTH is frequently applied in medicine, in particular for functional tests, for example, of the adrenal cortex, or for the treatment of neurologic and rheumatoid disorders, skin diseases, and disorders of the gastrointestinal tract as well as for adjuvant therapy of oncologic patients. Several analogs of ACTH have been introduced, one of the most frequently used being Synacthen, the ACTH[1–24] fragment.

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