Homologous desensitization of human corticotropin-releasing factor1 receptor in stable transfected mouse fibroblast cells

Brain Research
K D DieterichE B De Souza

Abstract

Previous radioligand binding and second messenger studies have shown that corticotropin-releasing factor (CRF) modulates its receptor following both in vivo and in vitro treatment. In the present study, we determined the sequence of events leading to CRF-induced downregulation and desensitization of cloned CRF receptors in murine fibroblast cells (Ltk-) stably transfected with CRF1 DNA (from human pituitary). Treatment of cells with rat/human CRF produced a dose- and time-dependent decrease in [125I]Tyr degrees-ovine CRF ([125I]oCRF) binding and a concomitant decrease in CRF-stimulated adenylate cyclase activity. Significant decreases in [125I]oCRF binding and agonist-stimulated cAMP production were evident minutes after CRF treatment with maximal (60-80%) reductions seen following 1 h of CRF treatment. Scatchard analysis revealed that the decrease in [125I]oCRF binding was due to the downregulation of the receptor with no significant alteration seen in the affinity of the ligand. Since the transfected cell line is engineered using an artificial promoter, we did not detect any significant changes in CRF1 receptor mRNA levels following CRF treatment for up to 24 h.

References

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Citations

May 8, 2003·The Journal of Pharmacology and Experimental Therapeutics·Richard L HaugerFrank M Dautzenberg
Aug 16, 2018·Physiological Reviews·Jan M Deussing, Alon Chen
Apr 6, 2002·Archives of Physiology and Biochemistry·D MasonP Thompson
Mar 17, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Robert H OakleyRichard L Hauger
Jul 23, 2020·Trends in psychiatry and psychotherapy·Mailton VasconcelosRosa Maria M de Almeida
May 12, 2004·Peptides·Greti AguileraKevin J Catt

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