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

Journal Article · Tue Jan 01 04:00:00 EST 1991 · Endocrine Research; (United States)

DOI:https://doi.org/10.1080/07435809109027187· OSTI ID:5029691

Olson, M F; Tsao, J; Pon, D J; Schimmer, B P ^[1]

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1. Banting and Best Department of Medical Research, University of Toronto, Ontario (Canada)

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 beta 2-adrenergic receptor (beta 2-AR). Transfectants expressed beta 2-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. The authors demonstrate that beta-adrenergic agonists desensitize the adenylyl cyclase system in transfected Y1DS cells whereas transfected Y1DR cells are resistant to desensitization by beta-adrenergic agonists. The fate of the beta 2-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 beta-adrenergic agonists. The extent of receptor loss induced by beta-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.

• OSTI ID: 5029691
• Journal Information: Endocrine Research; (United States), Journal Name: Endocrine Research; (United States) Vol. 17:1-2; ISSN ENRSE; ISSN 0743-5800
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ADRENAL GLANDS
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BIOLOGICAL PATHWAYS
BODY
CYCLASES
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENDOCRINE GLANDS
ENZYME ACTIVITY
ENZYMES
GENES
GLANDS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LYASES
MAMMALS
MEMBRANE PROTEINS
MICE
MUTATIONS
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
RECEPTORS
RODENTS
SYMPATHOMIMETICS
TRACER TECHNIQUES
TUMOR CELLS
VERTEBRATES