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The Receptors Of Adrenergic By Dr. Sara Sami Yuzuncu Yil University 2015

Adrenal antagonist agent

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Page 1: Adrenal antagonist agent

The Receptors Of Adrenergic

By Dr. Sara SamiYuzuncu Yil University

2015

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Adrenergic Receptors• These are mainly 2 types

(α) Alfa

(β) Beta

(D) De

These are again subdivided into various types

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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

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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

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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

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Potency of catecholamines on Adrenergic Receptors

Adr NA

Iso

Iso Adr

NA

Log Concentration

Aortic strip contraction Bronchial relaxation

α β

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Molecular Effector Differences – α -β

– α Receptors:• IP3/DAG

• cAMP

• K+ channel opening

– β Receptors:• cAMP

• Ca+ channel opening

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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

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PKc

Also Recall: Phospholipase C: IP3-DAG pathway

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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

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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

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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

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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)

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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

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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

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Molecular Basis of Adrenergic Receptors

Also glycogenolysis in liver

Inhibition of Insulin release and Platelet aggregationGluconeogenesis

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Dopamine receptors• D1-receptors are post synaptic receptors

located in blood vessels and CNS

• D2-receptors are presynaptic present in CNS, ganglia, renal cortex

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ADRENERGIC RECEPTORS

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