Problem 2 - Brenner and Stevens’ Pharmacology

Question

G protein-coupled receptors that activate an inhibitory \(\mathrm{G}_\alpha\) subunit alter the activity of adenylate cyclase to (A) increase the coupling of receptor to \(\mathrm{G}\) protein. (B) block the ligand from binding. (C) initiate the conversion of GTP to GDP. (D) generate intracellular inositol triphosphate. (E) decrease the production of cAMP.

Step-by-Step Solution

Answer

Option (E) decrease the production of cAMP.

Step 1: Understanding G Protein-Coupled Receptors (GPCRs)

G protein-coupled receptors are a large family of cell surface receptors that respond to various external signals. When a ligand binds to a GPCR, it activates an associated G protein by causing the exchange of GDP for GTP on the G protein's alpha subunit.

Step 2: Different G Protein Types

There are different types of G protein alpha subunits, including G_s, G_i, and G_q. The G_i (inhibitory) subunit causes a decrease in adenylate cyclase activity, thereby reducing cyclic AMP (cAMP) production.

Step 3: Function of Adenylate Cyclase

Adenylate cyclase is an enzyme that converts ATP to cyclic AMP (cAMP). cAMP serves as a second messenger that carries signals inside the cell.

Step 4: Identifying the Effect of G_i on Adenylate Cyclase

When an inhibitory G_i protein is activated by a GPCR, it inhibits adenylate cyclase, leading to a decrease in the production of cAMP.

Step 5: Analyzing Answer Choices

Review the provided options to determine which one aligns with the knowledge that the inhibitory G_i decreases cAMP production. - (A) Incorrect, because increased receptor-G protein coupling is not the primary effect. - (B) Incorrect, as blocking ligand binding is not related to G_i function. - (C) Incorrect, though GDP to GTP conversion is involved in G protein activation, not inhibition. - (D) Incorrect, this describes a pathway for G_q, not G_i. - (E) Correct, as it states the G_i effect of reducing cAMP production.

Key Concepts

adenylate cyclase

Adenylate cyclase is a crucial enzyme found on the inside surface of the cell membrane. It serves an essential role in the cellular signaling pathways. This enzyme is responsible for converting adenosine triphosphate (ATP) into cyclic AMP (cAMP), a process essential for transmitting signals inside cells. When activated, adenylate cyclase increases the levels of cyclic AMP, which acts as a second messenger. This second messenger is involved in regulating various physiological processes, such as glycogen breakdown and lipid metabolism. Adenylate cyclase can be regulated by signals originating from G protein-coupled receptors (GPCRs). GPCRs can activate or inhibit adenylate cyclase activity, depending on the type of G protein they are associated with. This means adenylate cyclase can either boost or reduce cAMP production based on the signals received from outside the cell.

cyclic AMP (cAMP)

Cyclic AMP (cAMP) is a pivotal second messenger in numerous biological processes. It is involved in the relay of signals from extracellular proteins, such as hormones and neurotransmitters, which bind to cell surface receptors. One of the key functions of cAMP is to activate protein kinase A (PKA), a crucial player in many signaling pathways. When cAMP binds to PKA, it triggers a cascade of events leading to the relaxation of heart muscles or the breakdown of glycogen in the liver, among other actions.cAMP levels in the cell can be modified by the activity of adenylate cyclase, which converts ATP into cAMP. When adenylate cyclase is inhibited, for instance by the inhibitory G protein alpha subunit (\( ext{G}_i \)), cAMP production drops, affecting downstream signaling pathways.

G protein alpha subunits

G protein alpha subunits are part of the larger heterotrimeric G proteins, which are key in transmitting signals from GPCRs to various intracellular targets. These subunits play a crucial role in determining the effect of GPCR activation on the cell.Three main types of alpha subunits are \( ext{G}_s \) (stimulatory), \( ext{G}_i \) (inhibitory), and \( ext{G}_q \). The \( ext{G}_s \) subunit activates adenylate cyclase, resulting in increased cAMP levels. On the other hand, the \( ext{G}_i \) subunit inhibits adenylate cyclase, decreasing cAMP production, thereby dampening the signals inside the cell. When a ligand binds to a GPCR, these alpha subunits can either exchange GDP for GTP (activating the signal) or, in the case of \( ext{G}_i \), inhibit pathways that lead to cAMP reduction. Understanding the specific alpha subunit type activated is key to predicting the cellular response to external signals.