Alpha/beta receptors in action
Slowly ascending 400 feet to the top of the first hill, you are assured that it was worth waiting in the long line for this roller coaster. Your heart beats fast as you grip the steering wheel tightly with your sweaty palms.
You scream as you speed up the first hill, turning and taking many sharp turns. When the ride ends, you walk off the roller coaster with a trembling hand, a pounding heart, and an overwhelming sense of adrenaline and excitement.
Situations similar to the above that cause fear, anxiety, danger, excitement, or stress will trigger our sympathetic nervous system to act on adrenergic receptors and trigger a fight or flight response.
There are 2 main types of adrenergic receptors: alpha and beta.
Alpha adrenergic receptors discussed earlier.
This post will now focus on the different types of beta adrenergic receptors and the effects they cause.
As with all EZmed topics, you will also learn simple content retention strategies.
So what are adrenergic receptors?
If you are coming herealpha adrenergic receptorblog post, you can skip to the next section below as this is for reference.
Adrenergic receptors are found on tissue and organ cells throughout the body and are the target of catecholamines such as epinephrine and norepinephrine.
These catecholamines are mainly influenced by:sympathetic nervous system.
When sympathetic activity increases, postganglionic sympathetic neurons release norepinephrine to adrenergic receptors in target tissues and organs.
In addition, sympathetic preganglionic neurons that terminate in the adrenal medulla cause the release of noradrenaline and epinephrine from the adrenal glands into the bloodstream.
Norepinephrine released from postganglionic sympathetic neurons and epinephrine and noradrenaline released from the adrenal medulla will bind to adrenergic receptors in target organs and trigger the sympathetic fight or flight response.
Activation of adrenergic receptors in the heart will modify itcardiac action potentialspacemaker cells and contractile myocytes to increase heart rate and cardiac contractility, which will improve cardiac output.
Activation of adrenergic receptors in the vessels leads to vasoconstriction and an increase in systemic vascular resistance. In addition to the increased cardiac output mentioned above, vasoconstriction will increaseBlood pressureto improve blood flow to vital organs.
Activation of adrenergic receptors will also lead to bronchodilation in open airways, pupil dilation to optimize vision and gluconeogenesis to increase glucose levels to meet the demands of increased metabolism during the fight or flight response.
Below is a reminder of the sympathetic events that occur prior to the activation of the adrenergic receptors discussed earlierautonomic nervous system.
This blog will now be a continuation and a more detailed discussion of adrenergic receptors, their location and the effects they cause.
It is worth noting that in the future there will be a similar post discussing cholinergic receptors from the parasympathetic side.
As discussed above, beta-adrenergic receptors are involved in triggering the sympathetic fight-or-flight response when catecholamines such as norepinephrine and epinephrine bind to them.
Although both norepinephrine and epinephrine can act on beta receptors, epinephrine has a greater affinity for beta receptors compared to norepinephrine, especially for beta2 receptors where there is little or no activity of norepinephrine. More on that later.
This is in contrast to what we have seen with alpha receptors, where norepinephrine has a higher affinity than epinephrine.
This makes sense when we think of norepinephrine and epinephrine as anti-stress drugs used to treat various medical conditionstypes of shock.
Epinephrine has quite a beta effect and some alpha while norepinephrine has quite an alpha effect and some beta.
Therefore, epinephrine has a greater effect on the heart/cardiac output and lungs/bronchodilation (beta receptors), while norepinephrine has a greater effect on the vessels/vasoconstriction (alpha receptors).
For this reason, epinephrine is given during anaphylaxis because it has a much higher affinity for beta2 receptors in the lungs, which causes bronchodilation and relief of respiratory distress.
General smooth muscle function
Now that we have a good understanding of the affinity for beta receptors, let's discuss the general effect that beta receptors have on involuntary smooth muscle when activated.
Activation of beta receptors leads to smooth muscle relaxation.
For example, one of the main sites of beta receptors is in the lungs, and their activation will lead to bronchodilation by relaxing smooth muscles.
This is in contrast to what we observed with alpha receptors, the activation of which led to smooth muscle contraction (vasoconstriction, urethral sphincter spasm, pylorus spasm, prostate spasm, iris dilator spasm, etc.).
Below are some tricks to help you remember the affinity of the receptors and the effect each receptor has on smooth muscle.
In terms of alpha receptors, think of alphas in the animal kingdom, which are dominant and powerful. This will keep you in mind that alpha receptors lead to smooth muscle contraction.
For beta receptors, consider betta fish.
Betta fish can be territorial and fight each other (to help you remember that beta receptors are involved in the fight-or-flight response). However, when left alone, betta fish are relaxed - this will keep you in mind that beta receptors lead to smooth muscle relaxation.
Types of beta receptors
Let's now discuss each of the beta receptors in more detail.
There are 3 main types of beta receptors: beta1, beta2 and beta3.
All beta receptors are coupled to Gs proteins that increase cAMP levels.
Beta1 receptors are pretty easy to remember as there are 2 main places to keep in mind: the heart and the kidneys.
When activated, the beta1 receptors in the heart will increase the heart rate and contractility of the heart.
The heart rate will increase by activating the beta1 of the SA node, the AV node and the conduction system of the heart.
It will increasephase 4 action potentialtilting of the pacemaker cells, causing more frequent depolarization.
Activation of Beta1 will also increase the contractility of the heartphase 2 of the action potentialcardiac myocytes, which increases stroke volume.
Remember that heart rate and stroke volume are two variables that determine cardiac output.
If both are elevated, cardiac output will increase. This will increase the increased cardiac outputBlood pressureand perfusion.
But wait, I thought we said beta receptors lead to muscle relaxation?
Remember, this involved smooth muscle, not the heart.
Beta1 receptors are also found in the kidneys, especially in the juxtaglomerular (JG) cells.
Activation will lead to the release of renin from the JG cells, which will initiate it renin-angiotensin-aldosterone system(RAAS).
The RAAS will then lead to the production of angiotensin II and all its downstream effects to improve blood pressure.
If you haven't checked ithypotensionpost, I highly recommend it as it will combine the synergistic effects of the sympathetic nervous system and the RAAS in raising blood pressure.
Beta2 receptors bind to Gs proteins such as beta1.
Increasing the level of cAMP in structures with beta2 receptors will lead to smooth muscle relaxation, as mentioned earlier.
Some of the main sites for β2 receptors include the lungs, gastrointestinal tract, bladder, uterus, pancreas, and blood vessels.
Since we know that beta2 receptors lead to smooth muscle relaxation, we now know that beta2 receptors in these places will do just that.
Activation of beta2 in the lungs will lead to smooth muscle relaxation and bronchodilation during the sympathetic response.
The relaxation of the smooth muscles of the stomach and intestines due to the activation of β2 will lead to a decrease in gastric contraction and a decrease in intestinal peristalsis.
This coupled with the alpha1 pyloric and anal sphincter stenosis seen at the alpha-adrenergic site will lead to reduced digestion during the sympathetic response.
The relaxation of the bladder wall by activating the beta2 receptor will lead to urinary retention and reduced urination.
We can also link this to the alpha1 urethral sphincter contraction we observed.
We see how alpha1 urethral sphincter contraction coupled with beta2 bladder wall relaxation will synergistically cause urinary retention and decreased urination.
The relaxation of the uterus after activation of the beta2 receptors will lead to the inhibition of labor.
Beta2 receptors are found in blood vessels and lead to vascular smooth muscle relaxation and vasodilation.
But wait, we learned in the alpha adrenergic post that alpha1 receptors are found in blood vessels and lead to vasoconstriction.
Don't we want vasoconstriction, not vasodilation, to increase peripheral vascular resistance and blood pressure during the sympathetic response?
Won't alpha1 and beta2 receptors on blood vessels cancel each other out?
Here's the answer.
The amount of alpha 1 and beta 2 receptors varies in blood vessels depending on the structure to which they supply blood.
Organs such as skin and the digestive tract are not as essential for immediate survival during the fight-or-flight response.
Therefore, the arterial supply to these non-essential organs will be greater with alpha1 receptors. This will constrict the vessels and reduce the blood supply to them, and redirect blood flow to other more important vital organs.
For example, the heart is an important structure during the sympathetic response.
It would be harmful if the coronary arteries consisted mainly of alpha1 receptors.
Vasoconstriction during the sympathetic response would result in decreased coronary flow and insufficient oxygen delivery to the heart.
As a result, coronary arteries express more β2 receptors compared to peripheral vessels to maintain some degree of vasodilation and blood flow to the heart.
Arterioles in skeletal muscle also express β2 receptors, and alpha1 receptors are attenuated to allow increased blood flow to skeletal muscle during the fight-or-flight response.
In conclusion, the number of alpha 1 and beta 2 receptors in blood vessels varies depending on the organ they supply.
In addition, the total number of alpha1 receptors far exceeds the number of beta2 receptors, which is why blood pressure ultimately rises during the sympathetic response.
Pancreas, liver, eye
Beta2 receptors are also found in the pancreas and liver, leading to increased insulin release and gluconeogenesis/glycogenolysis, respectively, to increase glucose and energy production during the fight or flight response.
Beta2 receptors are also found in the eye, which increases the production of aqueous humor.
Beta3 receptors are also associated with the Gs protein.
They are of less clinical importance.
They are located mainly in adipose tissue, and after activation, lipolysis occurs.
It has recently been shown that beta3 receptors can also be located in the bladder detrusor muscle, which together with beta2 receptors helps to relax the bladder.
This will be covered in more detail in future posts, however, it can be appreciated that beta-adrenergic receptors can be a useful drug target.
There are beta-blockers, some beta1-selective and some non-selective, that can help treat high blood pressure, arrhythmias, heart failure, essential tremor, glaucoma, etc.
Activation of beta-adrenergic receptors may also be clinically relevant.
For example, epinephrine is useful in anaphylaxis, where activation of the beta1 and beta2 receptors relieves respiratory distress by expanding the bronchi and helps maintain blood pressure.
Other depressants that have a higher affinity for beta receptors, such as dobutamine, could potentially be useful adjuncts in cases ofcardiogenic shock.
Specific beta2 agonists such as albuterol may also be useful in treating asthma or COPD to relievebreathing difficulties.
Pheochromocytoma is a tumor of the adrenal glands that causes elevated levels of adrenaline and norepinephrine, leading to overactivity of the sympathetic nervous system.
Anticholinergic toxicitywill lead to uninterrupted sympathetic activity by blocking the cholinergic receptor.
The use of cocaine, methamphetamines and stimulants can also induce compassion.
We hope this helped simplify beta-adrenergic receptors.
Beta adrenergic receptors are one of the two main adrenergic receptors, the other being alpha receptors.
They are involved in generating a sympathetic response when activated by catecholamines such as norepinephrine or epinephrine.
Both norepinephrine and epinephrine can act on beta receptors, however epinephrine generally has a higher affinity.
Beta1 receptors are found mainly in the heart and kidneys. They lead to increased fibrotropy/chronotropy and renin release, respectively.
Beta2 receptors lead to smooth muscle relaxation. They are found in the lungs, bladder, digestive tract, blood vessels, and uterus, respectively, and lead to bronchodilation, bladder wall relaxation/urine retention, bowel relaxation/digestion reduction, vasodilation, and labor inhibition, respectively.
Beta3 receptors are found in adipose tissue, which leads to lipolysis and the bladder, which leads to relaxation of the bladder.
There are drugs that can act as beta receptor antagonists or agonists, blocking or facilitating the sympathetic response.
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