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The Receptors Of Adrenergic
By Dr. Sara SamiYuzuncu Yil University
2015
Adrenergic Receptors• These are mainly 2 types
(α) Alfa
(β) Beta
(D) De
These are again subdivided into various types
How Many of them ????
Alpha (α) Beta (β)
Adenoreceptors
α 1 β3β 2β1α 2
α 2B α 2Cα 2A
α 1A α 1B α 1D
Adrenergic Receptors
• Adrenergic receptors (or adrenoceptors) are a class of G-protein coupled receptors that are the target of catecholamines
• Adrenergic receptors specifically bind their endogenous ligands– catecholamines (adrenaline and noradrenline)
– Increase or decrease of 2nd messengers cAMP or IP3/DAG
• Many cells possess these receptors, and the binding of an agonist will generally cause the cell to respond in a flight-fight manner.
– For instance, the heart will start beating quicker and the pupils will dilate
Differences - Adrenergic Receptors (αand β) !
• Alpha (α) and Beta (β)
• Agonist affinity of alpha (α):
– adrenaline > noradrenaline > isoprenaline
–Antagonist: Phenoxybenzamine
– IP3/DAG, cAMP and K+ channel opening
• Agonist affinity of beta (β):
– isoprenaline > adrenaline > noradrenaline
–Propranolol
– cAMP and Ca+ channel opening
Potency of catecholamines on Adrenergic Receptors
Adr NA
Iso
Iso Adr
NA
Log Concentration
Aortic strip contraction Bronchial relaxation
α β
Molecular Effector Differences – α -β
– α Receptors:• IP3/DAG
• cAMP
• K+ channel opening
– β Receptors:• cAMP
• Ca+ channel opening
Recall: Adenylyl cyclase: cAMP pathway
PKA Phospholamban
Increased Interaction with Ca++
Faster relaxation
Troponin
Cardiac contractility
OtherFunctionalproteins
PKA alters the functions of manyEnzymes, ion channels, transportersand structural proteins.
Faster sequestration of Ca++ in SR
PKc
Also Recall: Phospholipase C: IP3-DAG pathway
Beta receptors• All β receptors activate adenylate cyclase, raising the intracellular
cAMP concentration• Type β1:
– These are present in heart tissue, and cause an increased heart rate by acting on the cardiac pacemaker cells
• Type β2:– These are in the vessels of skeletal muscle, and cause
vasodilatation, which allows more blood to flow to the muscles, and reduce total peripheral resistance
– Beta-2 receptors are also present in bronchial smooth muscle, and cause bronchodilatation when activated
– Stimulated by adrenaline, but not noradrenaline– Bronchodilator salbutamol work by binding to and stimulating the
β2 receptors• Type β3:
– Beta-3 receptors are present in adipose tissue and are thought to have a role in the regulation of lipid metabolism
Differences between β1, β2 and β3
Beta-1 Beta-2 Beta-3
Location Heart and JG cells Bronchi, uterus,
Blood vessels,
liver, urinary tract,
eye
Adipose
tissue
Agonist Dobutamine Salbutamol -
Antagonist Metoprolol, Atenolol Alpha-methyl
propranolol
-
Action on
NA
Moderate Weak Strong
Clinical Effects of β-receptor stimulation• β1: Adrenaline, NA and Isoprenaline:
– Tachycardia
– Increased myocardial contractility
– Increased Lipolysis
– Increased Renin Release
• β2: Adrenaline and Isoprenaline (not NA)
– Bronchi – Relaxation
– SM of Arterioles (skeletal Muscle) – Dilatation
– Uterus – Relaxation
– Skeletal Muscle – Tremor
– Hypokalaemia
– Hepatic Glycogenolysis Hypoglcmia and hyperlactiacidemia
• β3: Increased Plasma free fatty acid – increased O2 consumption - increased heat production
Adrenergic receptors - alpha• Type α1
– Blood vessels with alpha-1 receptors are present in the skin and the genitourinary system, and during the fight-or-flight response there is decreased blood flow to these organs
– Acts by phospholipase C activation, which forms IP3 and DAG
– In blood vessels these cause vasoconstriction• Type α2
– These are found on pre-synaptic nerve terminals– Acts by inactivation of adenylate cyclase, cyclic
AMP levels within the cell decrease (cAMP)
adrenoceptorsClinical effects
• Eye -- Mydriasis
• Arterioles – Constriction (rise in BP)
• Uterus -- Contraction
• Skin -- Sweat
• Platelet - Aggregation
• Male ejaculation
• Hyperkalaemia
• Bladder Contraction
• α2 adrenoceptors on nerve endings mediate negative feedback which inhibits noradrenaline release
Differences between α1 and α2
Alpha-1 Alpha-2
Location Post junctional – blood vessels
of skin and mucous
membrane, Pilomotor muscle
& sweat gland, radial muscles
of Iris
Prejunctional
Function Stimulatory – GU,
Vasoconstriction, gland
secretion, Gut relaxation,
Glycogenolysis
Inhibition of transmitter
release, vasoconstriction,
decreased central symp.
Outflow, platelet
aggregation
Agonist Phenylephrine, Methoxamine Clonidine
Antagonist Prazosin Yohimbine
Molecular Basis of Adrenergic Receptors
Also glycogenolysis in liver
Inhibition of Insulin release and Platelet aggregationGluconeogenesis
Dopamine receptors• D1-receptors are post synaptic receptors
located in blood vessels and CNS
• D2-receptors are presynaptic present in CNS, ganglia, renal cortex
ADRENERGIC RECEPTORS