Question

Epinephrine increases the heart rate and causes the bronchioles (airways) to dilate by using cyclic AMP as a second messenger. Suppose a drug increased the cyclic AMP in heart and bronchiolar smooth muscle cells; what effects would the drug have? Could you give a person intravenous cyclic AMP and duplicate the action of epinephrine? Explain.

Short answer

A drug that increases cyclic AMP levels in heart and bronchiolar smooth muscle cells would likely have similar effects as epinephrine, increasing heart rate and causing dilation of the airways. However, intravenous administration of cyclic AMP would not be a practical way to duplicate the action of epinephrine due to its poor cell membrane permeability, rapid degradation by phosphodiesterases, and potential for off-target effects.

Step-by-step solution

Understanding the role of cyclic AMP as a second messenger

Cyclic AMP (cAMP) acts as a second messenger in the signaling cascade initiated by the binding of epinephrine to its receptor on the target cells. Upon binding, the receptor activates an enzyme called adenylate cyclase, which converts ATP to cyclic AMP. The increase in cyclic AMP levels inside the cell causes the activation of protein kinase A (PKA), which in turn phosphorylates other proteins, leading to various cellular responses. In the case of heart cells, this cascade results in an increase in heart rate, while in bronchiolar smooth muscle cells, it causes dilation of the airways.

Effects of a drug that increases cyclic AMP

If a drug increases the cyclic AMP levels in heart and bronchiolar smooth muscle cells, it will likely have similar effects as epinephrine. In heart cells, an increase in cyclic AMP would lead to an increased heart rate, while in bronchiole smooth muscle cells, the increase in cyclic AMP would result in dilation of the airways. Thus, the drug would have the same physiological effects as epinephrine in these tissues.

Intravenous administration of cyclic AMP

Administering cyclic AMP intravenously may not be as effective as epinephrine in producing the desired responses in heart rate and bronchiole dilation for several reasons. Firstly, cyclic AMP is a highly polar molecule and would not easily cross the cell membrane to enter the target cells. Secondly, even if cyclic AMP could enter the cells, it could be rapidly degraded by intracellular phosphodiesterases, which breakdown cyclic AMP to maintain homeostasis. Lastly, the intravenous administration of cyclic AMP could possibly affect other tissues and organs that also utilize cyclic AMP as a second messenger, leading to unintended and potentially harmful side effects. In summary, while a drug that increases cyclic AMP levels in heart and bronchiolar smooth muscle cells would have similar effects as epinephrine, intravenous administration of cyclic AMP would not be a practical way to duplicate the action of epinephrine due to its poor cell membrane permeability, rapid degradation by phosphodiesterases, and potential for off-target effects.

Key concepts

Epinephrine Mechanism of Action

Epinephrine, commonly known as adrenaline, plays a critical role in the 'fight or flight' response by exerting effects on various tissues including the heart and lungs. When epinephrine binds to its receptors, known as adrenergic receptors, on the surface of target cells, it initiates a powerful cascade of events.

One pivotal player in this process is cyclic AMP (cAMP), which acts as a second messenger. The binding of epinephrine triggers the activation of an enzyme called adenylate cyclase, located on the inner surface of the cell membrane. This enzyme catalyzes the conversion of ATP to cAMP, resulting in an increase in the intracellular concentration of cAMP.

The elevated levels of cAMP then activate protein kinase A (PKA), which goes on to phosphorylate various target proteins within the cell. This phosphorylation leads to changes in cell function, such as increased heart rate and dilation of the bronchioles, which are vital adaptive responses during stress or vigorous activity.

Adenylate Cyclase Function

Adenylate cyclase serves as a fundamental component in the signal transduction pathways of many hormones and neurotransmitters. In the context of epinephrine's effect on cells, adenylate cyclase's principal function is converting ATP into cyclic AMP (cAMP).

This reaction is an essential step in the signaling cascade because cAMP acts as a second messenger, relaying the initial signal from epinephrine's binding on the cell surface deeper into the cell interior. Here, it ignites the activation of protein kinase A and other downstream effectors. The efficient role of adenylate cyclase guarantees a rapid and amplified response to the hormone, allowing the cells to respond swiftly to external signals.

Protein Kinase A Activation

Protein Kinase A (PKA) lies at the heart of many cellular processes, functioning as a regulatory enzyme that modulates various physiological reactions by phosphorylating proteins on serine and threonine residues.

The activation of PKA is intimately linked to the role of cAMP. As cAMP levels rise in response to signals like epinephrine, it binds to the regulatory subunits of PKA, causing a conformational change that releases the catalytic subunits. These catalytic subunits of PKA are now free to phosphorylate target proteins, causing alterations in their activity that contribute to the physiological effects such as increased cardiac output or smooth muscle relaxation in the bronchioles.

Physiological Effects on Heart Rate

The increase in heart rate is among the most notable effects when epinephrine interacts with cardiac cells. Upon activation by cAMP and subsequent PKA phosphorylation events, the heart muscle cells increase their rate and force of contraction.

This response is physiologically significant during stress or exercise, as it ensures that the body can supply enough oxygen and nutrients by increasing the circulation of blood. The heart achieves this elevated rate by modifying the activity of ion channels and calcium handling proteins within cardiac cells, thereby accelerating the pacemaker activity and enhancing the strength of myocardial contractility.

Bronchiole Smooth Muscle Dilation

Another essential effect of epinephrine is the dilation of bronchiole smooth muscle. This process, medically referred to as bronchodilation, is pivotal for increasing airflow to the lungs, enhancing oxygen uptake, and facilitating carbon dioxide release.

The activation of PKA in bronchiolar smooth muscle cells leads to the phosphorylation of proteins that reduce intracellular calcium concentrations, resulting in relaxation of the smooth muscle tissue. This cAMP-induced relaxation allows the airways to expand, aiding in easier and more effective breathing, particularly under conditions where the body's demand for oxygen is heightened.