Today, we are going to talk about two endogenous substances, extremely important for the homeostasis of our organism and for special situations, as we will see below.
You will certainly hear for the rest of your life talking about adrenaline and norepinephrine, especially in emergencies.
And we will see, today, how important they are to the functioning of our organism, and you will understand why it is worth studying very hard about these substances.
Before talking about the functions and effects of catecholamines, we need to know who produces them, what is their origin.
Catecholamines are essential substances to the adrenergic response in our body. And you can ask yourself, ” When do I need an adrenergic response?” .
There are so many situations, that we will talk in detail below. But what you have is a response to the stress generated, facing a situation of danger or fear.
Recalling that, physiologically we have both the sympathetic and parasympathetic nervous systems at work, but they are in balance.
In response to stress, the sympathetic system is exacerbated, mediated by catecholamines.
The norepinephrine , also known as norepinephrine, NOR, NA, NS is produced by the postganglionic sympathetic nerve endings and, to a lesser extent, by cells of the adrenal medulla.
In the CNS, specifically in the brain stem, a nucleus is located that has the main neurotransmitter to be released, noradrenaline, which is the locus coeruleus, which means “blue spot”, due to the pigmentation resulting from melanin granules, having been discovered in 1786 .
Already adrenaline , also called epinephrine, ADR or E, is produced by cells of the adrenal medulla.
When we are in a situation of stress or fear, for example, a stimulus is sent to the hypothalamus, which releases CRH, the Corticotrophin Releasing Hormone.
This hormone travels to the adenohypophysis, and stimulates the production of ACTH. ACTH in turn falls into the bloodstream and reaches the adrenal gland , stimulating the production of glucocorticoids, such as cortisol, and adrenaline.
In addition, the released glucocorticoids stimulate areas in the central nervous system to produce and release norepinephrine.
To act in our organism, like most substances present in our organism, catecholamines need to bind to specific receptors.
These receivers will vary depending on where they are. The action is systemic, with actions you may not even imagine.
The receptors to which catecholamines bind to exert their effects are alpha (α1 and α2) and beta ( β 1 and β 2) adrenergic drugs.
Let’s talk about the action in each of these receivers and where they are.
Catecholamines acting on α1 receptors
Do you remember the G protein-coupled receptors? This is one of them. The receptor is coupled to Gq protein.
Once activated, it activates Phospholipase C, promoting an increase in IP3 (inositol triphosphate) and DAG (diacylglycerol), and ultimately leading to an increase in calcium.
Both catecholamines (NOR and ADR), act on α1.
The receptor is present in the eyeball. One of the actions of the stimulation is the increase of calcium, leading to the contraction of the radial muscle of the iris and thus promoting mydriasis, that is, it promotes dilation of the pupil.
This occurs, physiologically in a stress or flight situation, in order to increase the field of vision.
In some situations, where it is necessary to promote mydriasis, as in fundus examination, it is common to use agonists, that is, a drug that produces sympathomimetic effects.
Because they are also present in blood vessels, another extremely important effect is vasoconstriction. They are present in skin vessels, mucous membranes and even in the vessels of abdominal viscera.
Vasoconstriction increases peripheral vascular resistance (PVR), thereby increasing blood pressure (BP = DC x PVR ). In addition, it also contracts the venous vessels, causing an increase in venous return.
The gastrointestinal tract also has α1 receptors, and the action of catecholamines at that location is to promote sphincter contraction, and thus reduces the deflation of the GIT, since once the sphincters close, the content present in the GIT cannot pass.
Our organism thinks about everything, because if you are running away from something, your energy is diverted to processes necessary to escape, in addition to preventing defecation at those times.
In the urinary system, the activation of α1 receptors also promotes sphincter contraction, but this time it is the bladder sphincter, as well as the ureter contraction. What happens? Reduces urination. And it makes perfect sense, doesn’t it !?
Imagine yourself in a situation of stress or flight … do you feel like urinating? Yes, there is not, because the body understands the situation, and prepares you to face it, and in situations like this you cannot stop to go to the bathroom, right !!?
Α1 receptors are also present in the respiratory system, where their action is to reduce bronchial secretion. That is, it increases the air passage.
It also acts on α1 of some glands. The sweat glands, for example, are stimulated to produce sweat, but it is a ‘different’ sweat, it is called adrenergic sweat, as it is more viscous, odorous and cold due to vasoconstriction, in addition to being preferably located on extremities, such as on the face , armpits, hands, feet and inguinal region.
The salivary glands are also activated, producing a thicker saliva, causing the sensation of dry mouth.
There is also piloerection, it gets “creepy”.
And an effect that you may not even imagine catecholamines can play by acting on α1 is ejaculation. That’s right !!
The prostate, the vas deferens and the seminal vesicles have receptors, and when activated they promote contraction of such structures, and thus the semen is propelled causing ejaculation.
He saw how two substances can cause so many effects, completely different, in the most diverse places of the organism. And we only saw the α1 effects. Many effects are yet to follow.
Catecholamines acting on α2 receptors
When catecholamines bind to α2 receptors, which are coupled to Gi protein, there is inhibition of adenylcyclase, reducing cAMP, and thus increasing the conductance to potassium (K + ).
Α2 effects can occur at the presynaptic terminal and at the postsynaptic terminal. The most important are presynaptic effects. But why?
When catecholamines act on α2 at the presynaptic terminal, they promote a negative modulation to the release of norepinephrine, promoting self-regulation of the release.
And the importance of this process is enormous, since it prevents you from having an adrenergic over-stimulation in the body.
The effects on α2 at the post-synaptic terminal are vasoconstriction and reduced insulin secretion by the pancreas.
Catecholamines acting on β adrenergic receptors
Beta-adrenergic receptors ( β1 and β 2) are also coupled to protein G, specifically to Gs. When activating Gs, activation of adenylcyclase occurs, which in turn increases cAMP.
This is the signaling cascade that occurs so that different effects can happen. We will see below the effects of the activation of the different receptors.
Catecholamines acting on β1 receptors
Β1 receptors are present in some important organs of our body. The way in which these receptors are activated has been described above.
The heart, an organ essential to life, has β1 receptors in both the contractile myocardium and the specialized myocardium. Upon turning on, a number of cardiac effects can happen.
One of these effects is the increase in inotropism (it is the force of the heart’s contraction). There is also an increase in heart rate, and thus the heart contracts more times per minute, pumping more blood, and thus increases cardiac output (DC = VS x FC).
The entire contraction process is triggered by a nervous stimulus, originated by the specialized myocardium. Since the heart is “accelerated”, this stimulus must also “accelerate”, which is why the effect of catecholamines on β1 receptors in the specialized myocardium is to increase the speed of conduction of the stimulus.
But with all this increase, in heart rate, driving, and inotropism, there is a great potential for arrhythmias to occur.
And we must not forget that once the heart rate and cardiac output have increased, there is also an increase in blood pressure (BP = DC x RVP).
Many effects occur in the heart, but it is not the only organ that has β1 receptors . The justaglomerular apparatus also has these receptors. But what is justaglomerular apparatus?
The justaglomerular apparatus is located in the kidneys, specifically in the nephrons. The renal corpuscle (renal glomerulus + Bowman’s capsule) has a vascular pole and a urinary pole. The justaglomerular apparatus is located at the vascular pole.
This device is composed of mainly afferent and efferent arterioles. Some cells in these arterioles undergo modification and become justaglomerular cells, secreting renin.
The cells of the macula densa (cells that arise from the wall of the distal tubule adjacent to the renal corpuscle), which monitor the concentrations of Na + and Cl – , and transmit the information to the justaglomerular cells.
And in the composition of the justaglomerular apparatus, we also have extraglomerular mesangial cells.
Now that you know what the justaglomerular device is, let’s see what catecholamines, with their sympathetic activity, can do. This device, as already mentioned, has β1 receptors .
When activated, justaglomerular cells are stimulated to increase renin secretion. When renin is secreted, SRAA (Renin Angiotensin Aldosterone System) is activated.
Renin is converted to angiotensin I, which in turn is converted to angiotensin II, which then promotes vasoconstriction, thereby increasing blood pressure. In addition, angiotensin II is converted to aldosterone, which increases absorption of Na + and H2O, and secretes K + .
That is, it increases the volume, also contributing to the increase in blood pressure.
You must be realizing how different effects are repeated even if by the action of catecholamines in different receptors, as occurs in relation to blood pressure, where several mechanisms act in order to increase it.
But continuing the effects of catecholamines on β1 , let’s talk about the gastrointestinal tract (TGI).
Catecholamines, acting in the TGI, promote reduced motility, thus reducing peristalsis, precisely for reasons that we have already discussed, the organism is preparing for escape activities.
Catecholamines acting on β 2 receptors
And now let’s talk about the sympathetic action of catecholamines when acting on β 2 receptors .
The signaling cascade occurs from the Gs protein, as previously mentioned.
One of the first things you should be aware of in relation to β 2 receptors is that the catecholamine that binds to it is adrenaline. Don’t forget that !! Noradrenaline has no affinity for this receptor.
And thinking about the effects that can be generated, we have the activation of β 2 promoting relaxation of vascular smooth muscle and thus promoting vasodilation.
Another muscle that has receptors is the bronchiolar smooth muscle, and by promoting relaxation of this muscle it causes bronchodilation, in order to increase the air flow.
The β 2 action also relaxes the uterine smooth muscle. Relaxes the bladder muscles (detrusor muscle) and thereby increases the volume capacity of the bladder.
Some metabolic effects may also be noticed in β 2 adrenergic activation , such as increased insulin release.
The eyeball also has β 2 receptors , and when activated, they relax the ciliary muscle, promoting accommodation of distance vision.
And now a very important effect that occurs in the pre-synaptic nerve termination when adrenaline binds to β 2, is the positive modulation of the release of noradrenaline by the termination, that is, it increases the release of NOR, which will perform all its functions. sympathetic effects systemically, on the receptors we talked about earlier (α1, α2, β 1).
There are many effects, as you may have noticed, in addition to being essential.
Knowing these actions is essential for understanding different clinical situations and for studying pharmacology, for example.
You will need to know the physiological action of sympathetic amines to be able to understand the role of each medication (such as a beta blocker, or an alpha agonist).
