Stable expression of normal and mutant human ACTH receptor: study of ACTH binding and coupling to adenylate cyclase

Molecular and Cellular Endocrinology
Danielle NavilleMartine Begeot

Abstract

Point mutations of the human ACTH receptor have been reported in some patients with a familial glucocorticoid deficiency syndrome. To demonstrate that these mutations were responsible for the disease, it was necessary to develop a model in which characteristics of normal and mutant receptors could be studied. We have developed a stable expression model in order to characterize the human ACTH receptor by binding studies and functional coupling to adenylate cyclase. After confirmation of the stable integration of receptor constructs, ACTH dose-responses for the production of cAMP were carried out. The EC50 for ACTH were 2.9 +/- 0.2 x 10(-10) M and 2.4 +/- 0.8 x 10(-10) M, respectively, for two different clones stably expressing the normal human ACTH receptor. EC50 calculated for clones expressing either one of the two studied mutant receptors (C251F and D107N) were increased: 4.1 +/- 0.9 x 10(-9) M and 6.4 +/- 1.3 x 10(-9) M respectively. These values were similar to that obtained with M3 parental cells (4.7 +/- 0.8 x 10(-9) M). Binding studies were performed on the same clones. Scatchard analysis showed that clones expressing the normal receptor possessed high affinity binding sites for ACTH, with K(d) = 5.8 +/- 2.4 x 10(-10) M ...Continue Reading

References

Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·A PenhoatJ M Saez
Nov 12, 1987·The New England Journal of Medicine·E M SmithJ E Blalock
Aug 5, 1983·Science·C GormanB H Howard
Apr 1, 1995·Endocrine Journal·Y YamamotoI Morimoto
May 31, 1993·Annals of the New York Academy of Sciences·A N EberleV Chhajlani

❮ Previous
Next ❯

Citations

Mar 23, 2005·Archives of Histology and Cytology·Shin-Ichi IzumiTakehiko Koji
Apr 2, 2009·Journal of Endocrinological Investigation·Y SoltaniM Begeot
Sep 27, 2000·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·L L Elias, A J Clark
Sep 6, 2002·The Journal of Clinical Endocrinology and Metabolism·Christa E FlückWalter L Miller
Feb 24, 2001·Endocrine Research·A PenhoatM Bégeot
Feb 22, 2017·Frontiers in Endocrinology·Davids FridmanisJanis Klovins
Jun 24, 1998·Biochemical and Biophysical Research Communications·R MarchalA Penhoat
Jun 29, 2005·Peptides·Mohamed RachedArmelle Penhoat
Jan 8, 2011·European Journal of Pharmacology·Li F ChanAdrian J L Clark

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.