Alpha adrenergic receptor

INTRODUCTION:
  • Alpha-1 adrenergic receptor is a G protein Coupled Receptor (GPCR) associated with the Gq, heterotrimeric protein.
  • More responsive to Norepinephrine than to epinephrine.
  • Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α1-adrenergic receptor in the central and peripheral nervous systems.
Types of alpha receptors:
  • α-adrenoceptors exist on peripheral sympathetic nerve terminals and are divided into two subtypes α1, and α2.
  • α1 is found mostly postsynaptically, whilst α2 although typically sited presynaptically, can also occur postsynaptically.
  • Alpha 1 adrenergic receptor consists of three highly homologous subtypes, including α1A, α1B, α1D- adrenergic.
α-Adrenoceptor Location
  • Alpha 1 receptors are located on:
  1. All vascular smooth muscle, although densities vary throughout the body
  2. GI & urinary sphincters
  3. Dilator muscle of the iris
  4. Arrector pili muscle of hair follicles
  5. On central and peripheral nervous system
α-Adrenoceptor function:
α1 receptor:
  • Specific actions of the α1 receptor mainly involve smooth muscle contraction.
  • It causes vasoconstriction in many blood vessels, including those of the skin, gastrointestinal system, kidney (renal artery) and brain.
  • Thus Dale's vasomotor reversal is due to Alpha blocker
  • Other areas of smooth muscle contraction are:
  1. Ureter
  2. Vas deferens
  3. Hair (arrector pili muscles)
  4. Uterus (when pregnant)
  5. Urethral sphincter
  6. Urothelium and lamina propria
  • Bronchioles (although minor relative to the relaxing effect of β2 receptor on bronchioles)
  • Blood vessels of ciliary body (stimulation causes mydriasis)
  • Further effects include glycogenolysis and gluconeogenesis from adipose tissueand liver, as well as secretion from sweat glands and Na+ reabsorption from kidney.
  • Antagonists may be used primarily in hypertension, anxiety disorder, and panic attacks.
  • Tamsolusin is Alpha 1 a blocker used for BHP without any effect on blood pressure
α2 receptor:
  • There are also α2 receptors on the nerve terminal membrane of the post-synaptic adrenergic neuron.
  • There are 3 highly homologous subtypes of α2 receptors: α2A, α2Β, and α2C.
  • Selective alpha 2 agoinst used in glaucoma Brimonidine
  • Drug with beta adrenergic blocking, with antioxidant, with calcium channel blocking, with alpha 1 antagonist activity is Carvedilol
  1. Specific actions of the α2 receptor include:
  2. Inhibition of insulin release in the pancreas.
  3. Induction of glucagon release from the pancreas.
  4. Contraction of sphincters of the gastrointestinal tract
  5. Negative feedback in the neuronal synapses - presynaptic inhibition of norepinephrine (NE) release in CNS
  6. Increased thrombocyte aggregation
Signaling Cascade:
  • Agonists and antigonists Alpha 1 agonists vasoconstrictive agents they are used to reduce edema and inflammation.
  • Naphazoline, phenylephrine and propylhexedrine.
  • Alpha 1 antagonists causes vasodilation and decreased peripheral resistance; therefore they are used in the treatment of hypertension (prazosin).
  • Treatment of benign prostatic hyperplasia.
  • Tamsulosin is a subtype-selective alpha 1A receptor that has more specificity toward smooth muscle in genitourinary tract.


Receptor Agonist potency order Selected action of agonist Mechanism Agonists Antagonists
α1: A, B, D† Norepinephrine > epinephrine >> isoprenaline Smooth muscle contraction, mydriasis,
vasoconstriction in the skin,
mucosa and abdominal viscera & sphincter contraction of the GI tract and urinary bladder
Gq: phospholipase C(PLC) activated, IP3,and DAG, rise in calcium (Alpha-1 agonists)
Noradrenaline
Phenylephrine
Methoxamine
CirazolineXy
lometazoline
Midodrine
Metaraminol
Chloroethylclonidine
(Alpha-1 blockers)
Acepromazine
Alfuzosin
Doxazosin
Phenoxybenzamine
Phentolamine
Prazosin
Tamsulosin(BHP)
Terazosin
Trazodone(TCAs)
Amitriptyline
Clomipramine
Doxepin
Trimipramine
Typical and atypical antipsychotics
Antihistamines
(H1antagonists)
Hydroxyzine
α2: A, B, C Epinephrine = norepinephrine >> isoprenaline
(however do consider that a bit of Norepinephrine was already used in a1,
thus giving
Epinephrine a relatively stronger affinity in a2)
Smooth muscle mixed effects, norepinephrine (noradrenaline) inhibition, platelet activation Gi: adenylate cyclaseinactivated, cAMP down (Alpha-2 agonists)
Agmatine
Dexmedetomidine
Medetomidine
Romifidine
Clonidine
Chloroethylclonidine
Brimonidine
Detomidine
Lofexidine
Xylazine
Tizanidine
Guanfacine
Amitraz
(Alpha-2 blockers)
Phentolamine
YohimbineIdazoxan
Atipamezole
Trazodone
Typical and atypical antipsychotics
Exam Question
  • Alpha 1a blocker used for BHP without any effect on blood pressure is Tamsolusin
  • Dale's vasomotor reversal is due to Alpha blocker
  • Prazosin, Indoramine & Idazoxan are alpha blocker
  • Clonidine is Alpha 2 receptor agonist
  • In a hypertensive patient with glaucoma Alpha blocker is given
  • Alpha agonist Hypotension,Hypertension , Nasal decongestant
  • Selective alpha 2 agoinst used in glaucoma Brimonidine
Don't Forget to Solve all the previous Year Question asked on Alpha adrenergic receptor