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  • Title: Factors essential for desensitization of pigeon erythrocyte adenylate cyclase responsiveness in a cell-free system.
    Author: Popov KM, Bulargina TV, Severin ES.
    Journal: Biochem Int; 1985 May; 10(5):723-31. PubMed ID: 2409978.
    Abstract:
    Cell-free desensitization of the pigeon erythrocyte adenylate cyclase-coupled beta-adrenoreceptor system requires soluble cellular factors. Desensitization is observed when a mixture of cell membranes and the cytosol fraction are incubated with isoproterenol or cAMP and IBMX for 20 min at 37 degrees C. Mg2+ and ATP are also required for cell-free desensitization. When adenylate cyclase is maximally stimulated by isoproterenol or GTP-gamma-S, the decrement of activity is 45-50% and 20-25%, respectively. Adenylate cyclase desensitization may be also produced by preincubation of plasma membranes with the catalytic component of cAMP-dependent protein kinase. Cell-free desensitization is associated with functional uncoupling of the beta-receptor. This is evidenced by an impaired ability of receptors to form a high affinity, guanine nucleotide-sensitive complex with the agonist and by the increase of the lag-phase of adenylate cyclase activation by isoproterenol and GTP-gamma-S. These findings suggest that one possible mechanism for the development of desensitization in adenylate cyclase systems may be the phosphorylation of a component(s) of the beta-receptor-adenylate cyclase complex which results in impaired receptor-cyclase coupling.
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