WBR0444

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Physiology
Sub Category	SubCategory::Renal
Prompt	[[Prompt::A researcher is studying the intracellular signaling pathways of anti-diuretic hormone (ADH) prior to its terminal hormonal effects. He observes that ADH molecules have several different binding sites in renal tissues. Which of the following intracellular signaling pathways is utilized by ADH V2 receptors to increase water reabsorption in the collecting ducts?]]
Answer A	AnswerA::G-protein coupled receptor pathway that activates downstream protein kinase A
Answer A Explanation	AnswerAExp::This receptor-pathway corresponds to that of AVPR2, the receptor responsible for increasing aquaporin-2 surface expression.
Answer B	AnswerB::Receptor tyrosine kinase that activates the MAP Kinase signalling cascade
Answer B Explanation	AnswerBExp::This pathway inherent to growth factors, not ADH.
Answer C	AnswerC::G-protein coupled receptor pathway that activates downstream protein kinase C
Answer C Explanation	AnswerCExp::This receptor-pathway corresponds to that of AVPR1.
Answer D	AnswerD::G-protein coupled receptor pathway that inhibits the cAMP signalling pathway
Answer D Explanation	AnswerDExp::The Gi-protein coupled receptor pathway inactivates adenylyl cyclase. On the contrary, ADH activates adenylyl cyclase by acting on the Gs-coupled AVPR2 receptors.
Answer E	AnswerE::G-protein coupled receptor pathway that activates the phosphatidylinositol signalling pathway
Answer E Explanation	AnswerEExp::This receptor-pathway corresponds to that of AVPR1. The phosphatidylinositol pathway activates downstream protein kinase C.
Right Answer	RightAnswer::A
Explanation	[[Explanation::There are several signal transduction pathways utilized by receptors to conduct impulses or to execute downstream functions. Receptors are classified based on these downstream effector pathways. The major receptor subtypes are: G protein-coupled receptors, receptor tyrosine kinases, integrin-RTK receptors, toll-like receptors, ligand or voltage-gated ion channels, and nuclear and cytoplasmic receptors. It is important to note that the signaling pathway utilized by ADH V2 receptors (AVPR2) is different from ADH V1 receptors (AVPR1). The ADH V2 receptor is a G-protein coupled receptor that activates the stimulative regulative G-protein (Gs) pathway that activates adenylyl cyclase. The latter catalyzes the conversion of ATP to cyclic AMP (cAMP) that activates protein kinase A. The activity of PKA causes the insertion of aquaporin-2 (AQP2) channels (water channels) allowing water reabsorption down an osmotic gradient at the luminal surface of the collecting duct cells. ADH binds the AVPR2 receptors on the basolateral membrane of the cells lining the collecting ducts. On the other hand, ADH V1 utilizes another signaling pathway; the Gq-coupled receptor pathway that activates phospholipase C and ultimately leads to formation of inositol triphosphate (IP3) and diacyl glycerol (DAG) and activation of protein kinase C. Educational Objective: ADH V2 receptor activates the Gs-coupled receptor pathway that activates adenylyl cyclase. The latter catalyzes the conversion of ATP to cyclic AMP (cAMP) that activates protein kinase A leading to aquaporin-2 insertion on the luminal surface of collecting duct cells. References: Bruce Alberts. [et al.]; with problems by John Wilson, Tim Hunt. Molecular Biology of the Cell. Courier Corporation; 2007.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Intracellular signalling pathway, WBRKeyword::Signalling pathway, WBRKeyword::Signal transduction, WBRKeyword::Receptors, WBRKeyword::GPCR, WBRKeyword::G-protein coupled receptors, WBRKeyword::ADH, WBRKeyword::Vasopressin
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