alpha-1 (α₁) adrenergic receptors 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 group of evolutionarily-related p ...

(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 heterotrimeric complex. The biggest non-structu ...

. 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) 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. Catechol can be either a free molecule or a ...

s like

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

(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 and ...

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

central Central is an adjective usually referring to being in the center of some place or (mathematical) object. Central may also refer to: Directions and generalised locations * Central Africa, a region in the centre of Africa continent, also known a ...

and

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

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 an involuntary non- striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit ...

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 synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neur ...

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 and ...

Smooth muscle

In smooth muscle cells of

blood vessel Blood vessels are the structures of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away from ...

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 ve ...

. 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 cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

, 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 GI tract contains all the major organs of the digestive system, in humans and ...

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

(

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 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 special ...

. During the

fight-or-flight response The fight-or-flight or the fight-flight-or-freeze response (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 desc ...

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 urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...

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

Ureter The ureters are tubes made of smooth muscle that propel urine from the kidneys to the urinary bladder. In a human adult, the ureters are usually long and around in diameter. The ureter is lined by urothelial cells, a type of transitional e ...

Uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...

(when pregnant): this is minor compared to the relaxing effects of the β₂ receptor, agonists of which - notably albuterol/salbutamol - were 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 male or female external urethral sphincter and the internal urethral sphincter. When either of th ...

Bronchioles The bronchioles or bronchioli (pronounced ''bron-kee-oh-lee'') 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 o ...

(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 spokelike ...

Page 163 *

Seminal tract The seminal tract is a part of the male reproductive system and consists of Seminiferous tubules ( Tubuli seminiferi recti, Rete testis, Efferent ducts), Epididymis ( Appendix), Vas deferens (Ampulla An ampulla (; ) was, in Ancient ...

, resulting in

ejaculation Ejaculation is the discharge of semen (the ''ejaculate''; normally containing sperm) from the male reproductory tract as a result of an orgasm. It is the final stage and natural objective of male sexual stimulation, and an essential compone ...

Neuronal

Activation of α₁-adrenergic receptors produces

anorexia Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...

and partially mediates the efficacy of appetite suppressants like

phenylpropanolamine Phenylpropanolamine (PPA) is a sympathomimetic agent which is used as a decongestant and appetite suppressant. It was commonly used in prescription and over-the-counter cough and cold preparations. In veterinary medicine, it is used to cont ...

and

amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

in the treatment of

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...

. 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 p ...

, 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 agonist, excitato ...

excitatory

postsynaptic potential Postsynaptic potentials are changes in the membrane potential of the postsynaptic terminal of a chemical synapse. Postsynaptic potentials are graded potentials, and should not be confused with action potentials although their function is to ini ...

s by the activation of α₁-adrenergic receptors. Norepinephrine also stimulates serotonin 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 is an agent 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 contraction. The term ''inotr ...

effects on

heart muscle Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate Muscle tissue, muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striat ...

* Secretion from

salivary gland The salivary glands in 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 minor salivary glands. Salivar ...

* Increase salivary

potassium Potassium is the chemical element with the symbol K (from Neo-Latin '' kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosp ...

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. Mechanism ...

and

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

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

. * 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 pole of the Bowman's capsule to the beginning of loop of Henle. It can be further classified into the proximal convoluted tubule (PCT) and the proximal straig ...

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 mechanism of action of a ...

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, BrE: apnoea, is the temporal 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 airways are (patency), there may ...

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 p ...

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) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...

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) *

Methoxamine Methoxamine is an α1-adrenergic receptor agonist, somewhat similar in structure to butaxamine and 2,5-DMA. It is no longer marketed. See also * Sertraline * Phenylephrine * Synephrine * Phentolamine * Midodrine Midodrine is a vasopres ...

( vasoconstrictor) *

Synephrine Synephrine, or, more specifically, ''p''-synephrine, is an alkaloid, occurring naturally in some plants and animals, and also in approved drugs products as its ''m''-substituted analog known as neo-synephrine. ''p''-Synephrine (or formerly Sympat ...

(mild vasoconstrictor) * Etilefrine ( antihypotensive) * Metaraminol ( antihypotensive) * Midodrine ( 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 adre ...

(

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 ...

) *

Norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

( vasoconstrictor) *

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 eyedrops to treat eye red ...

(

) *

Phenylephrine Phenylephrine is a medication primarily used as a decongestant, to dilate the pupil, to increase blood pressure, and to relieve hemorrhoids. In the United States, it was previously used orally as an over-the-counter decongestant to relieve na ...

(

) *

Pseudoephedrine Pseudoephedrine (PSE) is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It may be used as a nasal/sinus decongestant, as a stimulant, or as a wakefulness-promoting agent in higher doses. It was first charac ...

(

) * Tetrahydrozoline (

) * Xylometazoline (

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

Alfuzosin Alfuzosin, sold under the brand names Alfosoft and 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 relax ...

(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, inability to urinate, or loss ...

) *

Arotinolol Arotinolol (INN, marketed under the tradename Almarl) is a medication in the class of mixed alpha/beta blockers. It also acts as a β3 receptor agonist. A 1979 publication suggests arotinolol as having first been described in the scientific lite ...

* Carvedilol (used in

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...

; 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 di ...

(antipsychotic and powerful antihypertensive) *

Doxazosin Doxazosin, sold under the brand names Cardura among others, is a medication used to treat symptoms of benign prostatic hyperplasia (enlarged prostate) and hypertension (high blood pressure). For high blood pressure, it is a less preferred option ...

(used in hypertension and benign prostatic hyperplasia) *

Indoramin Indoramin (trade names Baratol and Doralese) is a piperidine antiadrenergic agent. It is an alpha-1 selective adrenoceptor antagonist with direct myocardial depression action; therefore, it results in no reflex tachycardia. It is also used in be ...

* Labetalol (used in hypertension; it is a mixed alpha/beta adrenergic antagonist) * Moxisylyte * Phenoxybenzamine * Phentolamine (used in

hypertensive emergencies A hypertensive emergency is very high blood pressure with potentially life-threatening symptoms and signs of acute damage to one or more organ systems (especially brain, eyes, heart, aorta, or kidneys). It is different from a hypertensive urgency ...

; it is a nonselective alpha-antagonist) *

Prazosin Prazosin is an α1 blocker medication primarily used to treat high blood pressure, symptoms of an enlarged prostate, and nightmares related to post-traumatic stress disorder (PTSD). It is a less preferred treatment of high blood pressure. Oth ...

(used in hypertension) *

Quetiapine Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its ...

* Risperidone * Silodosin *

Tamsulosin Tamsulosin, sold under the brand name Flomax among others, is a medication used to treat symptomatic benign prostatic hyperplasia (BPH) and chronic prostatitis and to help with the passage of kidney stones. The evidence for benefit with a ki ...

(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 effect ...

Tiamenidine Tiamenidine ( BAN, USAN, INN, also known as thiamenidine, Hoe 440) is an imidazoline compound that shares many of the pharmacological properties of clonidine. It is a centrally-acting α2 adrenergic receptor agonist ( IC50 = 9.1 nM). It ...

* Tolazoline *

Trazodone Trazodone, sold under many brand names, is an antidepressant medication. It is used to treat major depressive disorder, anxiety disorders, and difficulties with sleep. The medication is taken orally. Common side-effects include dry mouth, fee ...

Trimazosin Trimazosin is a sympatholytic alpha-1 blocker Alpha-1 blockers (also called alpha-adrenergic blocking agents or alpha-1 antagonists) constitute a variety of drugs that block the effect of catecholamines on alpha-1-adrenergic receptors. They a ...

* 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 chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness ...

s and

antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range o ...

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, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s like

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...

, and headaches due to excessive vasodilation.

References

External links

* {{Adrenergics Adrenergic receptors