Agonist-induced desensitization of adenylyl cyclase in Y1 adrenocortical tumor cells

Olson, M. F. , Tsao, J., Pon, D. J. and Schimmer, B. P. (1991) Agonist-induced desensitization of adenylyl cyclase in Y1 adrenocortical tumor cells. Endocrine Research, 17(1-2), pp. 19-42. (doi: 10.1080/07435809109027187) (PMID:1679008)

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Y1 adrenocortical tumor cells (Y1DS) and Y1 mutants resistant to ACTH-induced desensitization of adenylyl cyclase (Y1DR) were transfected with a gene encoding the mouse ß-adrenergic receptor (ß-AR). Transfectants expressed ß-ARs that were able to stimulate adenylyl cyclase activity and steroid biosynthesis. These transfectants were used to explore the basis for the DR mutation in Y1 cells. We demonstrate that ß-adrenergic agonists desensitize the adenylyl cyclase system in transfected Y1DS cells whereas transfected Y1DR cells are resistant to desensitization by ß-adrenergic agonists. The fate of the ß-ARs during desensitization was evaluated by photoaffinity labelling with [125I] iodocyanopindolol diazerine. Desensitization of Y1DS transfectants was accompanied by a modest loss in receptor density that was insufficient to account for the complete loss of responsiveness to ß-adrenergic agonists. The extent of receptor loss induced by ß-adrenergic agonists in Y1DR transfectants exceeded that in the Y1DS transfectants indicating that the mutation which protects Y1DR cells from agonist-induced desensitization is prior to receptor down-regulation in the desensitization pathway. From these results we infer that ACTH and isoproterenol desensitize adenylyl cyclase by a common pathway and that receptor loss is not a major component of the desensitization process in these cells.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Olson, Professor Michael
Authors: Olson, M. F., Tsao, J., Pon, D. J., and Schimmer, B. P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Endocrine Research
Publisher:Taylor & Francis
ISSN (Online):1532-4206

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