alpha-1 (α₁) adrenergic are

G protein-coupled receptors G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large protein family, group of evoluti ...

(GPCRs) associated with the G_q

heterotrimeric G protein Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a Heteromer, heterotrimeric complex. The biggest no ...

. α₁-adrenergic receptors are subdivided into three highly homologous subtypes, i.e., α_1A-, α_1B-, and α_1D-adrenergic receptor subtypes. There is no α_1C receptor. At one time, there was a subtype known as α_1C, but it was found to be identical to the previously discovered α_1A receptor subtype. To avoid confusion, naming was continued with the letter D.

Catecholamine A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Cate ...

s like

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

(noradrenaline) and

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

(adrenaline) signal through the α₁-adrenergic receptors in the central and

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of Bilateria, bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside t ...

s. The crystal structure of the α_1B-adrenergic receptor subtype has been determined in complex with the inverse agonist (+)-cyclazosin.

Effects

The α₁-adrenergic receptor has several general functions in common with the α₂-adrenergic receptor, but also has specific effects of its own. α₁-receptors primarily mediate

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

contraction, but have important functions elsewhere as well. The

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

norepinephrine has higher affinity for the α₁ receptor than does the hormone

adrenaline Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

Smooth muscle

In smooth muscle cells of

blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...

s the principal effect of activation of these receptors is

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

. Blood vessels with α₁-adrenergic receptors are present in the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

, the sphincters of

gastrointestinal system The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

(

renal artery The renal arteries are paired arteries that supply the kidneys with blood. Each is directed across the crus of the diaphragm, so as to form nearly a right angle. The renal arteries carry a large portion of total blood flow to the kidneys. Up to ...

) and

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

. During the

fight-or-flight response The fight-or-flight or the fight-flight-freeze-or-fawn (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first describ ...

vasoconstriction results in decreased blood flow to these organs. This accounts for the pale appearance of the skin of an individual when frightened. It also induces contraction of the internal urethral sphincter of the

urinary bladder The bladder () is a hollow organ in humans and other vertebrates that stores urine from the Kidney (vertebrates), kidneys. In placental mammals, urine enters the bladder via the ureters and exits via the urethra during urination. In humans, the ...

, although this effect is minor compared to the relaxing effect of β₂-adrenergic receptors. In other words, the overall effect of sympathetic stimuli on the bladder is relaxation, in order to inhibit

micturition Urination is the release of urine from the bladder through the urethra in placental mammals, or through the cloaca in other vertebrates. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, ures ...

upon anticipation of a stressful event. Other effects on smooth muscle are contraction in: *

Ureter The ureters are tubes composed of smooth muscle that transport urine from the kidneys to the urinary bladder. In an adult human, the ureters typically measure 20 to 30 centimeters in length and about 3 to 4 millimeters in diameter. They are lin ...

Uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...

(when pregnant): this is minor compared to the relaxing effects of the β₂ receptor, agonists of whichnotably albuterol/salbutamolwere formerly used to inhibit premature labor. *

Urethral sphincter The urethral sphincters are two muscles used to control the exit of urine in the urinary bladder through the urethra. The two muscles are either the external sphincter muscle of male urethra, male or external sphincter muscle of female urethra, fe ...

Bronchioles The bronchioles ( ) are the smaller branches of the bronchial airways in the lower respiratory tract. They include the terminal bronchioles, and finally the respiratory bronchioles that mark the start of the respiratory zone delivering air to t ...

(although minor to the relaxing effect of β₂ receptor on bronchioles) *

Iris dilator muscle The iris dilator muscle (pupil dilator muscle, pupillary dilator, radial muscle of iris, radiating fibers), is a smooth muscle of the eye, running radially in the iris and therefore fit as a dilator. The pupillary dilator consists of a spokelik ...

Page 163 * Seminal tract, resulting in

ejaculation Ejaculation is the discharge of semen (the ''ejaculate''; normally containing sperm) from the penis through the urethra. It is the final stage and natural objective of male sexual stimulation, and an essential component of natural conception. ...

Neuronal

Activation of α₁-adrenergic receptors produces

anorexia Anorexia nervosa (AN), often referred to simply as anorexia, is an eating disorder characterized by Calorie restriction, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. Individuals wit ...

and partially mediates the efficacy of appetite suppressants like

phenylpropanolamine Phenylpropanolamine (PPA), sold under many brand names, is a sympathomimetic agent used as a decongestant and appetite suppressant. It was once common in prescription and over-the-counter cough and cold preparations. The medication is taken ...

and

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

in the treatment of

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

. Norepinephrine has been shown to decrease cellular excitability in all layers of the

temporal cortex The temporal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain. The temporal lobe is involved in pr ...

, including the

primary auditory cortex The auditory cortex is the part of the temporal lobe that processes auditory information in humans and many other vertebrates. It is a part of the auditory system, performing basic and higher functions in hearing, such as possible relations to ...

. In particular, norepinephrine decreases

glutamatergic Glutamatergic means "related to glutamate". A glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/aspartate) system in the body or brain. Examples include excitatory amino acid receptor agonist ...

excitatory postsynaptic potentials by the activation of α₁-adrenergic receptors. Norepinephrine also stimulates

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

release by binding α₁-adrenergic receptors located on serotonergic neurons in the raphe. α₁-adrenergic receptor subtypes increase inhibition in the olfactory system, suggesting a synaptic mechanism for noradrenergic modulation of olfactory driven behaviors.

Other

* Both positive and negative

inotropic An inotrope or inotropic is a drug or any substance that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular co ...

effects on heart muscle * Secretion from

salivary gland The salivary glands in many vertebrates including mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands ( parotid, submandibular, and sublingual), as well as hundreds of min ...

* Increase salivary

potassium Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...

levels *

Glycogenolysis Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase. Mechanis ...

and

gluconeogenesis Gluconeogenesis (GNG) is a metabolic pathway that results in the biosynthesis of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In verte ...

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

. * Secretion from

sweat gland Sweat glands, also known as sudoriferous or sudoriparous glands, , are small tubular structures of the skin that produce sweat. Sweat glands are a type of exocrine gland, which are glands that produce and secrete substances onto an epithelial s ...

s * Contraction of the urinary bladder urothelium and lamina propria * Na⁺ reabsorption from

** Stimulate

proximal tubule The proximal tubule is the segment of the nephron in kidneys which begins from the renal (tubular) pole of the Bowman's capsule to the beginning of loop of Henle. At this location, the glomerular parietal epithelial cells (PECs) lining bowman’s ...

NHE3 Page 787 ** Stimulate

basolateral Na-K ATPase * Activate

mitogenic A mitogen is a small bioactive protein or peptide that induces a cell to begin cell division, or enhances the rate of division (mitosis). Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen. The cell cycle Mitogens ac ...

responses and regulate growth and proliferation of many cells * Involved in the detection of mechanical feedback on the hypoglossal motor neurons which allow a long-term facilitation in respiration in response to repeated

apnea Apnea (also spelled apnoea in British English) is the temporary cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the ...

Signaling cascade

α₁-Adrenergic receptors are members of the

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

superfamily. Upon activation, a

, G_q, activates

phospholipase C Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role i ...

(PLC), which causes

phosphatidylinositol Phosphatidylinositol or inositol phospholipid is a biomolecule. It was initially called "inosite" when it was discovered by Léon Maquenne and Johann Joseph von Scherer in the late 19th century. It was discovered in bacteria but later also found ...

to be transformed into inositol trisphosphate (IP₃) and diacylglycerol (DAG). While DAG stays near the membrane, IP₃ diffuses into the cytosol and to find the IP₃ receptor on the endoplasmic reticulum, triggering calcium release from the stores. This triggers further effects, primarily through the activation of an enzyme Protein Kinase C. This enzyme, as a kinase, functions by phosphorylation of other enzymes causing their activation, or by phosphorylation of certain channels leading to the increase or decrease of electrolyte transfer in or out of the cell.

Activity during exercise

During exercise, α₁-adrenergic receptors in active muscles are attenuated in an exercise intensity-dependent manner, allowing the β₂-adrenergic receptors which mediate vasodilation to dominate. In contrast to α₂-adrenergic receptors, α₁-adrenergic-receptors in the arterial vasculature of skeletal muscle are more resistant to inhibition, and attenuation of α1-adrenergic-receptor-mediated vasoconstriction only occurs during heavy exercise. Note that only active muscle α₁-adrenergic receptors will be blocked. Resting muscle will not have its α₁-adrenergic receptors blocked, and hence the overall effect will be α₁-adrenergic-mediated vasoconstriction.

Ligands

; Agonists * Cirazoline (

vasoconstrictor Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

) * Methoxamine (

) * Synephrine (mild

) *

Etilefrine Etilefrine, sold under the brand name Effortil among others, is a sympathomimetic medication used as an antihypotensive agent to treat orthostatic hypotension. It is usually used oral administration, by mouth, but is also available as an injecti ...

( antihypotensive) *

Metaraminol Metaraminol, also known as metaradrine and sold under the brand name Aramine among others, is a sympathomimetic medication which is used in the prevention and treatment of hypotension (low blood pressure), particularly as a complication of an ...

( antihypotensive) *

Midodrine Midodrine, sold under the brand names ProAmatine and Orvaten among others, is an antihypotensive medication used to treat orthostatic hypotension (low blood pressure when standing) and urinary incontinence. It is taken oral administration, by m ...

( antihypotensive) *

Naphazoline Naphazoline is a medicine used as a decongestant, and a vasoconstrictor added to eye drops to relieve red eye. It has a rapid action in reducing swelling when applied to mucous membranes. It is a sympathomimetic agent with marked alpha adrener ...

(

decongestant A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine (the latter o ...

) *

Norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

(

) *

Oxymetazoline Oxymetazoline, sold under the brand name Afrin among others, is a topical decongestant and vasoconstrictor medication. It is available over-the-counter as a nasal spray to treat nasal congestion and nosebleeds, as eye drops to treat eye rednes ...

(

) *

Phenylephrine Phenylephrine, sold under the brand names Neosynephrine and Sudafed PE among others, is a medication used as a decongestant for uncomplicated nasal congestion in the form of a nasal spray or oral tablet, to dilate the pupil, to increase bloo ...

(

) *

Pseudoephedrine Pseudoephedrine, sold under the brand name Sudafed among others, is a sympathomimetic medication which is used as a decongestant to treat nasal congestion. It has also been used off-label for certain other indications, like treatment of lo ...

(

) *

Tetrahydrozoline Tetryzoline (International Nonproprietary Name, INN), also known as tetrahydrozoline, is a drug used in some over-the-counter eye drops and nasal sprays. Tetryzoline was patented in 1954, and came into medical use in 1959. Side effects Tetryzol ...

(

) *

Xylometazoline Xylometazoline, also spelled xylomethazoline, is a medication used to reduce symptoms of nasal congestion, allergic rhinitis, and sinusitis. It is used directly in the nose as a spray or drops. Side effects include trouble sleeping, irritati ...

(

)
Sdz-nvi-085
04195-17-7 ; Antagonists * Acepromazine (antipsychotic, secondary mechanism) *

Alfuzosin Alfuzosin, sold under the brand name Uroxatral among others, is a medication of the α1 blocker class. It is used to treat benign prostatic hyperplasia (BPH). As an antagonist of the α1-adrenergic receptor, it works by relaxing the muscles ...

(used in

benign prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, urinary retention, inability t ...

) * Arotinolol *

Carvedilol Carvedilol, sold under the brand name Coreg among others, is a beta blocker medication, that may be prescribed for the treatment of high blood pressure (hypertension) and chronic heart failure with reduced ejection fraction (also known as HFrEF ...

(used in

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF typically pr ...

; it is a non-selective beta blocker) *

Chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar d ...

(antipsychotic and powerful antihypertensive) *

Doxazosin Doxazosin, sold under the brand name Cardura among others, is a medication used to treat symptoms of benign prostatic hyperplasia (enlarged prostate), hypertension (high blood pressure), and post-traumatic stress disorder (PTSD). For high bloo ...

(used in

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

and benign prostatic hyperplasia) * Indoramin * Labetalol (used in

; it is a mixed alpha/beta adrenergic antagonist) * Moxisylyte *

Phenoxybenzamine Phenoxybenzamine (PBZ, marketed under the trade names Dibenzyline and Dibenyline) is a non-selective, irreversible alpha blocker. Uses It is used in the treatment of hypertension, and specifically that caused by pheochromocytoma. It has a slowe ...

Phentolamine Phentolamine, sold under the brand name Regitine among others, is a reversible nonselective α- adrenergic antagonist. Mechanism Its primary action is vasodilation due to α1 blockade. Non-selective α-blockers can cause a much more pronounced ...

(used in hypertensive emergencies; it is a nonselective alpha-antagonist) *

Prazosin Prazosin, sold under the brand name Minipress among others, is a medication used to treat high blood pressure, symptoms of an enlarged prostate, and nightmares related to post-traumatic stress disorder (PTSD). It is an α1 blocker. It is a les ...

(used in hypertension) * Quetiapine *

Risperidone Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder, as well as aggressive and self-injurious behaviors associated with autism spectrum disorder. It is t ...

* Silodosin * Tamsulosin (used in benign prostatic hyperplasia) *

Terazosin Terazosin, sold under the brand name Hytrin among others, is a medication used to treat symptoms of an enlarged prostate and high blood pressure. For high blood pressure, it is a less preferred option. It is taken by mouth. Common side effec ...

* Tiamenidine *

Tolazoline Tolazoline is a non-selective Competitive antagonist, competitive Alpha blocker#Classification, α-adrenergic receptor antagonist. It is a vasodilator that is used to treat spasms of peripheral blood vessels (as in acrocyanosis). It has also been ...

Trazodone Trazodone is an antidepressant medication used to treat major depressive disorder, anxiety disorders, and insomnia. It is a phenylpiperazine compound of the serotonin antagonist and reuptake inhibitor (SARI) class. The medication is taken or ...

* Trimazosin * Urapidil Various

heterocyclic A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

s and

antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

s are α₁-adrenergic receptor antagonists as well. This action is generally undesirable in such agents and mediates

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s like

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...

, and headaches due to excessive vasodilation.

References

External links

* {{Adrenergics Adrenergic receptors Exercise biochemistry

Effects

Smooth muscle

Neuronal

Other

Signaling cascade

Activity during exercise

Ligands

See also

References

External links