Adrenoceptors Flashcards
What receptors detect noradrenaline from the sympathetic nervous system?
Adrenoreceptors:
Alpha
Beta
what is the agonist potency order for the alpha adrenoreceptors comparing noradrenaline, adrenaline and isoprenaline?
Alpha 1:
Noradrenaline > adrenaline»_space; isoprenaline
Alpha 2:
Adrenaline > Noradrenaline»_space; Isoprenaline
what is the agonist potency order for the beta adrenoreceptors comparing noradrenaline, adrenaline and isoprenaline?
Beta 1:
isoprenaline > noradrenaline > adrenaline
Beta 2:
isoprenaline > adrenaline > noradrenaline
Beta 3:
isoprenaline > noradrenaline = adrenaline
what is the structure of adrenoreceptors?
All adrenergic receptors are part of the family of G proteincoupled receptors (metabotropic receptors)
Recruit intracellular proteins, known as G proteins, in order to produce their cellular effects
Integral membrane protein
Single polypeptide chain: 400 - 500 amino acids
Extracellular N-terminus, intracellular C-terminus
7 transmembrane α helices
Binding site buried within a cleft between the α helices
How do alpha 1 adrenoreceptors lead to downstream signalling?
- Noradrenaline binds to its alpha 1 receptor.
- A change takes place in the Gq-protein where GDP is converted to GTP.
- This leads to the alpha subunit of the G-protein dissociating from the beta-gamma complex.
- The alpha subunit can diffuse in the membrane to interact with its target protein phospholipase C.
- Phospholipase C acts on PIP2 membrane phospholipid which produces IP3 and DAG.
- IP3 binds to the IP3 receptors on the surface of the ER and opens Ca ion channels leading to Ca release.
How do alpha 2 adrenoreceptors lead to downstream signalling?
Noradrenaline binds to its alpha 2 receptor.
- A change takes place in the Gi-protein where GDP is converted to GTP.
- This leads to the alpha subunit of the G-protein dissociating from the beta-gamma complex.
- The alpha subunit can diffuse in the membrane to interact with its target protein adenyl cyclase.
- The Gi-protein inhibits adenyl cyclase
- which leads to decreased cAMP levels and thus less activity of PKA
- Hence decreased phosphorylation of intracellular proteins.
- Produces effects of inhibition of neurotransmitter release.
give an example of an alpha 2 adrenoreceptor antagonist?
Yohimbine - used for treatment of sexual dysfunction.
How do beta adrenoreceptors lead to downstream signalling?
Noradrenaline binds to the beta adrenoreceptors.
1. This recruits Gs-protein
2. The Gs (G-protein) is converted from its GDP to GTP form
3. The alpha subunit dissociates and goes to activate the protein adenyl cyclase.
4. This leads to:
increased cAMP levels
increased activity of PKA
increased phosphorylation of intracellular proteins.
Produces the effect of relaxation of smooth muscle.
How can we target organs for drugs?
The 5 adrenoreceptors act upon different organs.
What is the function of adrenoreceptors on the heart?
Beta 1 adrenoreceptors: SAN - increased heart rate AVN - increased conduction velocity Atria - increased contractility Ventricles - increased contractility and enhance automaticity.
what adrenoreceptors are found in blood vessels and what are their affects on the smooth muscle.
alpha 1 (2) - constriction Beta 2 - dilation
what adrenoreceptors are found in bronchi and what are their affects on the smooth muscle.
Beta 2 - dilation
what adrenoreceptors are found in GIT and what are their affects on the smooth muscle.
Alpha 1, alpha 2 - contraction of sphincters
Beta 2 - relax
what adrenoreceptors are found in uterus and what are their affects on the smooth muscle.
alpha 1 - contract
beta 2 - relax
what adrenoreceptors are found in bladder and what are their affects on the smooth muscle.
Beta 3
What would be the effect of agonists (noradrenaline, adrenaline and isprenaline) on the cardiovascular system?
Noradrenaline - increased peripheral resistance to increase blood pressure
What are some adrenoreceptors agonists
α1 - phenylephrine
α2 - clonidine
β1 - dobutamine
β2 - salbutamol - terbutaline - salmeterol
β3 -mirabegron
What are some adrenoreceptor antagonists?
α1 - prazosin - doxazosin
α2 - yohimbine - idazoxan
β1 - atenolol - metoprolol
β2 - butoxamine
What is the function of adrenaline as an adrenoreceptor agonist?
activates both the alpha and beta agonist
used in cardiac arrest (to help restore cardiac rhythm)
What is the function of Dobutamine as an adrenoreceptor agonist?
Selective B1 receptor agonist.
Used in cardiogenic shock (acute heart failure)
What is the function of Salbutamol as an adrenoreceptor agonist?
Selective B2 receptor agonist
Used in asthma
What is the function of Mirabegron as an adrenoreceptor agonist?
Selective B3 receptor agonist.
Treatment of overactive bladder syndrome (OAB)
What is the function of Phenylephrine as an adrenoreceptor agonist?
Selective alpha 1 receptor agonist
Used for nasal decongestion
What are some uses of alpha adrenoreceptor antagonists?
Hypertension
Benign prostatic hypertrophy
Phaeochromocytoma
What are some uses of beta adrenoreceptor antagonists?
Cariovascular (hypertension, angina)
Glaucoma
What are the adverse effects of Beta adrenoreceptors antagonists
Bronchoconstriction worsening of cardiac failure bradycardia heart block hypoglycaemia physical fatigue cold extremities bad dreams
