Desensitization of the Human V2 Vasopressin Receptor. Homologous Effects in the Absence of Heterologous Desensitization
|Title:||Desensitization of the Human V2 Vasopressin Receptor. Homologous Effects in the Absence of Heterologous Desensitization|
|Authors:||Birnbaumer, Mariel; Antaramian, Anaid; Themmen, Axel P.N.; Gilbert, Stephanie|
|Publisher:||Journal of Biological Chemistry|
|Date Published:||June 15, 1992|
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
Receptors are molecular structures within cells or on the cell surface that bind with extracellular messengers such as hormones or neurotransmitters. There are receptors that stimulate the enzyme, adenylyl cyclase (AC). For example, the vasopressin-2 receptor (V2R), when bound with the antidiuretic hormone, arginine vasopressin (AVP), stimulates AC. AC, in turn, elevates cellular levels of cAMP. This molecular sequence is part of the sequence that allows the kidney to reabsorb water and concentrate urine.
V2Rs undergo desensitization, and Birnbaumer, et al., sought to clarify its desensitization process. The authors developed a cell line that expressed V2Rs. When this cell line was infused with AVP, it resulted in desensitization to AVP as indicated by a lessening of stimulation of AD. (As stated, when AVP first binds with V2R, it results in the stimulation of AD, which leads to kidney water reabsorption. But after it has done its job, the V2R must desensitize itself to AVP to temporarily turn off the water reabsorption process.)
The cells were cultured and treated with test substances such as AVP, prostaglandin E1 (PGE1) and a general prostaglandin inhibitor called IBMX. Then the cell cultures were tested for their levels of AVP/V2R binding, cAMP accumulations and AC stimulation. The authors wanted to know whether the V2R desensitization is induced by AVP itself, another agonist, or by activation of other receptors in the cell.
Desensitization may either be homologous or heterologous. It is homologous when it is caused by an agonist occupying a receptor, e.g. AVP occupying V2R. It is heterologous when the desensitization is caused by activation of other receptors that increase intracellular cAMP. For example, V2R desensitization would be heterologous if it was caused by some other receptor(s) in the cell culture increasing the cAMP levels.
The authors' experiments indicated that V2R desensitization is homologous. They concluded that AVP induces the V2R desensitization process, which is characterized by: