Talking about the Adrenal Receptors and its antagonist

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

2. Adrenergic Receptors
• These are mainly 2 types
(α) Alfa
(β) Beta
(D) De
These are again subdivided into various types

3. How Many of them ????
Alpha (α) Beta (β)
Adenoreceptors
α1
β3β2β1α2
α2B α2Cα2A
α1A α1B α1D

4. 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

5. Differences - Adrenergic Receptors (α
and 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

6. Potency of catecholamines on
Adrenergic Receptors
Adr NA
Iso
Iso Adr
NA
Log Concentration
Aortic strip contraction Bronchial relaxation
α β

7. Molecular Effector Differences – α -β
– α Receptors:
• IP3/DAG
• cAMP
• K+ channel opening
– β Receptors:
• cAMP
• Ca+ channel opening

8. Recall: Adenylyl cyclase: cAMP pathway
PKA Phospholamban
Increased
Interaction with
Ca++
Faster relaxation
Troponin
Cardiac
contractility
Other
Functional
proteins
PKA alters the functions of many
Enzymes, ion channels, transporters
and structural proteins.
Faster sequestration of
Ca++ in SR

9. PKc
Also Recall: Phospholipase C: IP3-DAG
pathway

10. 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

11. 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

12. 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

13. 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)

14. adrenoceptors
Clinical 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

15. 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

16. Molecular Basis of Adrenergic
Receptors
Also glycogenolysis in
liver
Inhibition of
Insulin release
and Platelet
aggregation
Gluconeogenes
is

17. Dopamine receptors
• D1-receptors are post synaptic receptors
located in blood vessels and CNS
• D2-receptors are presynaptic present in CNS,
ganglia, renal cortex

18. ADRENERGIC RECEPTORS