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