Last updated on January 10, 2019 at 20:01
|Catecholamines||Selective α-receptor agonists||Selective β-receptor agonists|
|Non-subtype selective||α1 selective||α2 selective||Non-subtype selective||β2 selective|
In the previous topic we saw some indirectly acting sympathomimetics. Now we’re going to look at some directly acting ones.
Adrenergic receptors, or adrenoceptors are the receptors that catecholamines can bind to. Seven types are important: α1, α2, β1, β2, β3, D1 and D2.
They’re all G-protein coupled receptors. Recall that depending on the type of G-protein on the inside of the cell will the activity of the receptor be different. Gs-type G-protein activates adenylyl cyclase, Gi type inhibits it and Gq type activates phospholipase C.
α1 receptor has a Gq type G-protein, meaning that when an agonist binds to it will phospholipase C be activated. The result will be activation of protein kinase C.
α2 receptor has Gi type G-protein, meaning it reduces the activity of adenylyl cyclase and therefore reduces the level of cAMP in the cell and inhibits protein kinase A. Recall from the previous topic that α2 receptor is part of the negative feedback, so it makes sense that it is inhibitory.
All β receptors are Gs coupled, meaning that they activate adenylyl cyclase and therefore increase the level of cAMP and activates protein kinase A.
Hint: An easy way to remember the G-proteins of α and β receptors is to remember the mnemonic “qiss”, which sounds almost like “kiss”. α1 has Gq, α2 has Gi, β1 has Gs and β2 has Gs.
D1 and D2 are the receptors for dopamine. D1 is Gs coupled as well and therefore activates protein kinase A. D2 is Gi coupled and therefore inactivates protein kinase A. D1 activates vasodilation of renal, splanchnic, coronary and cerebral vessels.
Not written in the table is the fact that β1 receptors stimulate renin release.
Catecholamines in clinical practice
Noradrenaline is used for severe hypotension, also during shock. Noradrenaline has mainly α1 and β1 receptor effects.
Adrenaline is used in cardiac arrest and anaphylactic shock. Locally it’s used to prolong local anaesthetic action and to stop bleeding.
Dopamine is used to treat shock. It’s also used to maintain renal perfusion.
Dobutamine is a synthetic (not endogenous) catecholamine that has most activity on β1-receptors, making it the only important β1-agonist. It is used in cardiogenic shock, because of the increased heart rate and contractility elicited by β1-receptors.
Isoprenaline is also a synthetic catecholamine. It has most activity on β receptors and is used in shock, Adams-Stokes syndrome and heart block.
Selective alpha receptor agonists
Phenylephrine is an α1 selective agonist. It has a long duration of action. It’s used to induce mydriasis (without cycloplegia) and as a decongestant.
Naphazoline, oxymetazoline and xylometazoline are α-selective. They’re used as decongestants.
Pholedrine is used to treat hypotonia, but is not clinically relevant anymore.
All α2-selective agonists decrease blood pressure by acting on α2-receptors in the vasomotor centre in the medulla oblongata. They are:
- Methyl-DOPA (converted to methyl-noradrenaline)
Selective beta receptor agonists
Recall from the previous topic that ephedrine is an indirectly acting sympathomimetic, however has direct effects as well. It has some direct effects on β receptors. It’s used to treat nasal congestion and hypotension.
The selective β2 agonists are used to treat asthma and to relax the uterus. By relaxing the uterus can they prevent abortion or premature labour. They are:
17. Agents acting on the biosynthesis, storage, release and elimination of catecholamines
19. Adrenergic receptor antagonists