Adrenergic Receptors Notes

Adrenergic receptors

-injection of adrenaline has two kinds of effects

-vasoconstriction in certain vascular beds: rise in arterial pressure

-vasodilation in other tissues

-If animal is injected with ergot, adrenaline caused a fall in arterial pressure

-This showed there were two different receptors and are classified according to the potency of catecholamines.

A: noradrenaline > adrenaline > isoprenaline

B: isoprenaline > adrenaline > noradrenaline

Key location and effects of adrenoreceptors

Receptor stimulation:

AGONIST: An agent binding to a receptor and stimulates a response

With sympathetic a & b receptors : agonist may be referred to as

-sympathetic agonist

-sympathomimetic agent/agonist

-adrenergic receptor

-adrenoreceptor agonist

-the agonist can act directly or indirectly (or a combination of both)

-Direct action on receptor

-noradrenaline/adrenaline/isoprenaline

-Indirect action to release noradrenaline

-tyramine, ephedrine, amphetamine (displaces NA from the storage vesicles)

Noradrenline and adrenaline

-these are non selective adrenoreceptor agonists – activates alpha and beta receptors. There is also a danger of ventricular fibrillation

-noradrenaline is more potent that adrenaline in activating alpha1, beta1 receptors

-adrenaline is more potent than noradrenaline in activating a2 and b2 receptorss

-its use is limited to severe acute conditions

Anaphylactic shock: reverses bronchospasm Heart stimulation (negative as it leads the ventricular dysrhythmias)

Acute cardiac failure: heart stimulation, vasoconstriction (negative as it increases peripheral resistance, this increases the workload of the heart

Also applied with local anaesthetics: the vasoconstriction mediated by the adrenaline increases the time period and increases the concentration of the local anaesthetic in a certain place.

Limits blood loss: vasoconstriction

Effects of adrenaline on vascular smooth muscle- resistance arterioles

Systemic blood vessels: majority are alpha 1 receptors, greater affinity to noradrenaline than adrenaline. Activated receptor triggers Gq protein- IP3- calcium- smooth muscle contraction

Cutaneous blood vessels: abundance of alpha 2 receptors, greater affinity for adrenaline than noradrenaline. Receptor is coupled to Gi protein, inhibits adenylate cyclase, less cyclic AMP –less activated protein kinase A-fall in K_ATP conductance-depolarisation-vasoconstriction

Arterial vessels of the myocardium/skeletal muscle/liver: alpha receptors and beta receptors are both present but beta 2 receptors have higher affinity. Beta 2 receptors are coupled to Gs proteins, increase in cyclic AMP, increase activation of protein kinase A-vasodilatation. Moderate increase in adrenaline dilates skeletal muscle and constricts in excess.

Alpha 1 adrenergic agonists

Alpha 1 receptors:

coupled to Gq proteins activates phospholipase C- breaks down phosphotidyl 4,5 bisphosphates into IP3/DAG

IP3 binds to its IP3 receptors on SR-opening of calcium channels- increased calcium-increased contraction

-the increase in calcium activates calcium activated chloride channels-depolarising current-leads to a slow rising excitatory junction potential

-DAG activates TRP channels, depolarising current creates a slow rising excitatory junction potential. DAG and increased calcium also activate protein kinase C which contributes to calcium sensitisation

Key effects:

-vascular and uterine smooth muscle contraction

-GI smooth muscle relaxation – increase in calcium leads to activation of eNOS – increased NO

-Salivary secretion

-glycogenolysis

Drugs

Phenylephrine:

Counter acute hypotension, treat nasal decongestion (causes vasoconstriction of blood vessels in the nose, reduce inflammation, reduce mucus secretion) causes mydriasis (dilatation of the pupil-contraction of the radial muscle)-used in ocular examination

Adv: metabolised by...

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