A research scientist develops an agent that specifically blocks the interaction of inositol triphosphate with its intracellular receptor. A study is then performed in which vascular smooth muscle cells are divided into 2 groups: an experimental group treated with the receptor blocker and an untreated control group. Both groups are exposed to phenylephrine. Compared to the control cells, decreased activity of which of the following enzymes is most likely to be observed in the experimental cells?

Question

A research scientist develops an agent that specifically blocks the interaction of inositol triphosphate with its intracellular receptor.  A study is then performed in which vascular smooth muscle cells are divided into 2 groups: an experimental group treated with the receptor blocker and an untreated control group.  Both groups are exposed to phenylephrine.  Compared to the control cells, decreased activity of which of the following enzymes is most likely to be observed in the experimental cells?

Quizplus · Accepted Answer

11ec160b_36bc_3d36_9249_f1c2f758e22b_MD0001_00 G protein-coupled receptors have a characteristic structure with 7 transmembrane regions, an extracellular domain, and an intracellular domain coupled with a G protein. In their inactivated state, G proteins exist as heterotrimers consisting of alpha, beta, and gamma subunits with GDP tightly bound to the alpha subunit. G proteins are activated after ligand binding to the extracellular domain of the receptor. The first step in activation occurs when GDP is exchanged for GTP on the alpha subunit. Once bound to GTP, the alpha subunit dissociates from the beta and gamma subunits and activates either adenylate cyclase or phospholipase C, depending on the ligand. When phenylephrine binds to an alpha-1 receptor on vascular smooth muscle cells, the alpha subunit of the G protein (G_q) activates phospholipase C, which breaks down phosphatidylinositol bisphosphate into inositol triphosphate (IP₃) and diacylglycerol (DAG). DAG stimulates protein kinase C, which phosphorylates downstream intracellular proteins to produce its physiologic effects (eg, smooth muscle contraction). IP₃ produces most of its effects by increasing intracellular calcium, which also activates protein kinase C. In the study described above, protein kinase C activity would be reduced in the experimental group compared to the control group as calcium release from the endoplasmic reticulum is interrupted. (Choice A) Activation of adenylate cyclase leads to the formation of cAMP and subsequent activation of protein kinase A. Protein kinase A phosphorylates intracellular proteins to produce its effects. (Choice B) Lipoxygenase is an enzyme responsible for the formation of leukotrienes from arachidonic acid. It is not directly involved in the phosphatidylinositol second messenger system. (Choice C) Phosphodiesterase is an enzyme that terminates the effects of ligands that act via cAMP or cGMP second messenger systems. It has no direct effect on the phosphatidylinositol second messenger system. (Choice D) The activity of phospholipase C would be unchanged if IP₃ were blocked because phospholipase C exerts its effect before IP₃ in the phosphatidylinositol second messenger system. Educational objective: After a ligand binds to a G protein-coupled receptor that activates phospholipase C, membrane phospholipids are broken down into diacylglycerol (DAG) and inositol triphosphate (IP₃). Protein kinase C is subsequently activated by DAG and calcium; the latter is released from the endoplasmic reticulum under the influence of IP₃. __________ References: G protein-dependent regulation of phospholipase C by cell surface receptors. (http://www.ncbi.nlm.nih.gov/pubmed/2155558) Role of inositol lipid breakdown in the generation of intracellular signals. State of the art lecture. (http://www.ncbi.nlm.nih.gov/pubmed/3013767)

A Research Scientist Develops an Agent That Specifically Blocks the Interaction