C2.1.10 Mechanism of action of epinephrine (adrenaline) receptors Notes

Epinephrine Triggers Rapid Body Responses Through cAMP Signaling

1. Imagine you’re running a race. Your heart pounds, your breathing quickens, and energy surges through your muscles.
2. This rapid response is orchestrated by epinephrine (also known as adrenaline), a hormone that prepares your body for action.
3. But how does epinephrine trigger these changes so quickly?
4. The answer lies in a sophisticated communication system involving receptors, G proteins, and a second messenger called cyclic AMP (cAMP).

Epinephrine Activates the Fight-or-Flight Response via Adrenergic Receptors

1. Epinephrine plays a critical role in the fight or flight response, activating various physiological changes in response to stress or danger.
2. The action of epinephrine is mediated through specific receptors, known as adrenergic receptors, which are part of the G protein-coupled receptor (GPCR) family.

Step 1: Epinephrine Binds to Its Receptor

1. Epinephrine is a hormone secreted by the adrenal glands during stress or excitement.
2. It travels through the bloodstream and targets specific cells, such as those in the heart, liver, and muscles.
3. These target cells have specialized proteins called G-protein-coupled receptors (GPCRs) embedded in their plasma membranes.
4. When epinephrine binds to its receptor, it triggers a conformational change (a change in shape) in the receptor.
5. This change is the first step in transmitting the signal into the cell.

Step 2: Activation of the G Protein

1. Attached to the inner side of the plasma membrane is a G protein, which acts as a molecular switch.
2. It consists of three subunits: alpha (α), beta (β), and gamma (γ).
3. In its inactive state, the alpha subunit is bound to a molecule called GDP (guanosine diphosphate).
4. When the receptor changes shape, it interacts with the G protein, causing the GDP to be released and replaced by GTP (guanosine triphosphate).
5. This exchange activates the G protein, which then dissociates into two parts: the alpha subunit (now bound to GTP) and the beta-gamma dimer.

Step 3: Activation of Adenylyl Cyclase

1. The activated alpha subunit of the G protein moves along the plasma membrane and binds to an enzyme called adenylyl cyclase.
2. This enzyme is responsible for converting ATP (adenosine triphosphate) into cyclic AMP (cAMP), a critical second messenger.

Step 4: cAMP Amplifies the Signal

1. Once produced, cAMP diffuses through the cytoplasm and activates a protein called protein kinase A (PKA).
2. PKA is an enzyme that phosphorylates (adds phosphate groups to) other proteins, altering their activity.
3. This phosphorylation cascade leads to a variety of cellular responses, depending on the target cell:
   1. In liver cells, it activates enzymes that break down glycogen into glucose, increasing blood sugar levels.
   2. In heart cells, it enhances the contraction of heart muscles, increasing heart rate and blood flow.
   3. In muscle cells, it promotes the breakdown of glycogen to provide energy for muscle contraction.

Step 5: Termination of the Signal

The effects of epinephrine are temporary, and the signal must be turned off to restore normal cellular function. This is achieved through several mechanisms:

1. Hydrolysis of GTP: The GTP bound to the alpha subunit is hydrolyzed back to GDP, inactivating the G protein.
2. Degradation of cAMP: An enzyme called phosphodiesterase breaks down cAMP into AMP, stopping the activation of PKA.
3. Dissociation of Epinephrine: The hormone eventually detaches from the receptor, returning it to its inactive state.

cAMP Amplifies Epinephrine's Signal for a Rapid and Robust Response

1. The use of cAMP as a second messenger allows for signal amplification.
2. A single molecule of epinephrine can lead to the production of thousands of cAMP molecules, each of which can activate multiple PKA molecules.
3. This amplification ensures a rapid and robust response to the hormone.

Standardized Naming in Science Promotes Global Collaboration and Clarity

1. The dual naming of epinephrine and adrenaline highlights the importance of international cooperation in science.
2. While both terms are widely used, standardization ensures clarity and consistency in scientific communication.