Alpha adrenergic receptor

INTRODUCTION:

• Alpha-adrenergic receptor –
  • Are G Protein-Coupled Receptor (GPCR) associated with Gq.
  • Heterotrimeric protein.
  • Generally, α-adrenoceptors exist on peripheral sympathetic nerve terminals.

TYPES:

• Divided into two subtypes α1 & α2.
• α1 – Mostly found postsynaptically.
  • Consists of three highly homologous subtypes – α1A, α1B, α1D.
• α2 – Typically sited presynaptically (also occur postsynaptically).

α-ADERNOCEPTOR LOCATION:

Alpha 1 receptors located on:

• All vascular smooth muscle (yet, varied densities throughout body).
• GI & urinary sphincters
• Dilator muscle of iris.
• Arrector pili muscle of hair follicles
• On central & peripheral nervous system.

Alpha 2 receptors located on:

• Some presynaptic terminals.
• Pancreatic Islets.
• Platelets.
• Ciliary epithelium.
• Smooth muscles.
• CNS neurons.

FUNCTIONS:

1. Alpha-1 receptor functions:

On smooth muscles:

Specific actions mainly smooth muscle contraction, including:

• Ureter.
• Vas deferens.
• Hair (arrector pili muscles).
• Uterus (when pregnant).
• Urethral sphincter.
• Urothelium and lamina propria.
• Bronchioles (although minor relative to relaxing effect of β₂ receptor on bronchioles).
• Blood vessels of ciliary body (stimulation causes mydriasis).

Causes vasoconstriction – 

• Mainly blood vessels of skin, GI system, renal artery & brain.
• Hence, Dale’s vasomotor reversal is due to Alpha blocker.

Other effects:

• Glycogenolysis & gluconeogenesis from adipose tissue & liver.
• Secretion from sweat glands.
• Na⁺ reabsorption from kidney.

Actions:

• Antagonists may be used primarily in hypertension, anxiety disorder, & panic attacks.
• Tamsulosin – Alpha 1 a blocker used for BHP without any effect on blood pressure

2. Alpha-2 receptor functions:

Difference between alpha-agonists & antagonists:

Alpha 1 agonists –

• Vasoconstrictive agents.
• Used to reduce edema and inflammation.
• Naphazoline, phenylephrine, and propylhexedrine.

Alpha 1 antagonists –

• Cause vasodilation.
• Decreases peripheral resistance.
• Used for hypertension (prazosin).
• Treatment of benign prostatic hyperplasia.

Receptor	Agonist potency order	Selected action of agonist	Mechanism	Agonists	Antagonists
α1: A, B, D†	Norepinephrine > epinephrine >> isoprenaline	Smooth muscle contraction. Mydriasis. Vasoconstriction in skin, mucosa & abdominal viscera. Sphincter contraction of GI tract & urinary bladder.	Gq: phospholipase C(PLC) activated, IP3 & DAG, rise in calcium	Noradrenaline Phenylephrine – Used as Mydriatic drug without cycloplegia. Methoxamine – Used in hypotension. Cirazoline Nasal decongestants: Naphazoline Oxymetazoline Xylometazoline Midodrine – Prodrug. Active form – desglymidodrine. Used for orthostatic hypotension. Metaraminol Chloroethylclonidine	(Alpha-1 blockers) Actions: Increases HDL & decreases LDL & TG. Causes smooth muscle relaxation, hence used for BHP. Drugs: Acepromazine Alfuzosin Doxazosin Phenoxybenzamine – Irreversible antagonist. Phentolamine & Tolazoline – Reversible antagonist. Prazosin – Treatment of Scorpion sting bite) Tamsulosin Used for BHP. Causes “Floppy iris syndrome” during cataract surgery. Terazosin Trazodone (TCAs) Amitriptyline Clomipramine Doxepin Trimipramine Typical and atypical antipsychotics Antihistamines (H1 antagonists) Hydroxyzine
α2: A, B, C	Epinephrine = norepinephrine >> isoprenaline (Epinephrine relatively stronger affinity in a2)	Smooth muscle mixed effects, norepinephrine (noradrenaline) inhibition, platelet activation	Gi: adenylate cyclase inactivated, cAMP down	Agmatine Dexmedetomidine – Pre-anesthetic medication Medetomidine Romifidine Alpha-methyldopa & Clonidine (Prodrug) Used for hypertension. Chloroethylclonidine. Topical application in Glaucoma: Brimonidine Apraclonidine. Others: Detomidine Lofexidine Xylazine Tizanidine – Muscle relaxant. Guanfacine Amitraz	(Alpha-2 blockers) Phentolamine Yohimbine Idazoxan Atipamezole Trazodone Typical and atypical antipsychotics

Don’t Forget to Solve all the previous Year Question asked on ALPHA ADRENERGIC RECEPTORS