Development of a Photoaffinity Probe for Adrenocorticotropin Receptors
Despite the enormous interest in the study of polypeptide hormone receptors, progress has been slow owing to the extremely small concentrations of receptors in target tissues. While some significant progress has been made in the case of peptide hormones that are acidic in character, such as human chorionic gonadotropin (Dufau et al., 1975) and prolactin(Shiu and Friesen, 1974), the identification of the specific receptors of the basic polypeptide hormones has proved to be much more difficult. Peptide hormones, especially those with isoelectric points above pH 8 [e.g., adrenocorticotropin (ACTH), melanocyte-stimulating hormone (MSH), glucagon], display a strong tendency to bind to a variety of inert materials as well as nonreceptor components of the target tissue. Since such binding appears specific by the criteria generally employed to define receptors and since the number of such nonreceptor sites greatly exceeds that of specific receptors (Cuatrecasas et al., 1975), the task of detecting and characterizing the physiologically relevant receptor is a formidable one. Fractiona-tion of the plasma-membrane components of the target cell on the basis of binding of the radioactive hormone may result in the isolation of nonreceptor components that may display high affinity for the hormone. Other approaches to the identification of the specific receptor are therefore necessary.
KeywordsACTH Receptor Photoaffinity Label High Specific Radioactivity Sulfenyl Chloride Single Tryptophan Residue
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