They are stimulated by the neurotransmitter acetylcholine, released at the nerve endings.
Hence along with the nicotinic receptors, they are called cholinergic receptors.
All the muscarinic receptors are G-protein coupled receptor types.
Unlike nicotinic receptors, showing response in milliseconds, muscarinic receptors respond in a few seconds to minutes.
Muscarinic Receptors types
There are five types of muscarinic receptors. They are divided based on their mechanism of response and their specific function.
The list of muscarinic receptors include
- M1 receptor
- M2 receptor
- M3 receptor
- M4 receptor
- M5 receptor
Of the five types M1, M2, and M3 are present in a significant proportion, while the other two are limited to nerve endings in the brain.
Further, the receptors M1, M3, M5 receptors work through the activation of the inositol phosphate pathway.
While the M2, M4 receptors inhibit adenylyl cyclase from reducing intracellular cyclic Adenosine Monophosphate (cAMP).
These receptors are located mainly in the central nervous system (CNS) in the regions like the cortex, hippocampus, striatum of the brain, and ganglionic cells.
The receptor is also called Gq muscarinic receptors as it is a Gq protein-coupled receptor.
They are also located in the peripheral neurons and the stomach parietal cells.
Functions of the M1 receptor
These receptors have excitatory effects in the CNS. They are primarily involved with the control of motor functions, learning, and memory,
In the stomach, they regulate gastric secretion under the influence of the vagus nerve.
These receptors mediate the release of histamine, which stimulates histamine (H2) receptors in the stomach to secrete hydrochloric acid.
M1 agonist and antagonist
This receptor is selectively stimulated by oxytremorine and antagonized by pirenzepine and telenzepine.
M2 receptors are majorly present in the heart and few visceral smooth muscles. They are also found in presynaptic terminals of central and peripheral neurons.
The function of M2 receptors
They have an inhibitory effect on the heart and also presynaptic neurons of central and peripheral neurons. This occurs due to the inhibition of calcium channels.
On the heart, their stimulation leads to a decrease in heart rate (bradycardia) and a reduction in contraction force.
Their actions are also responsible for analgesia and tremor in Parkinsonism.
M2 receptor agonist and antagonist
These are selectively stimulated by pilocarpine and antagonized by gallamine and methoctramine.
These receptors are primarily found in smooth muscles of the eye, blood vessels, intestine, and glands.
The glands include salivary glands, sweat glands, and those in the respiratory tract.
They control the constriction of the iris in the eye.
In the lungs, they are involved in bronchoconstriction.
They are also involved in dilating blood vessels by releasing nitric oxide, an endothelial relaxation factor.
On the glands, they enhance the secretion of the respective gland.
M3 receptor agonist and antagonist
These are selectively stimulated by bethanechol and antagonized by solifenacin and darifenacin.
They are thought to play a vital role in learning and drug abuse.
M4 receptor agonist and antagonist
Oxotremorine, an agonist for all the above receptors, is also a non-selective agonist for the M4 receptor. However, the selective antagonist is Ipratropium and Mamba toxin (a snake venom)
These are confined to the substantial nigra, striatum, hippocampus, midbrain pons medulla, cortex and cerebellum of CNS, and also the iris of the eye.
This receptor is thought to play an essential role in dopaminergic transmission in the brain. It also regulates salivary gland secretion and also pupillary constriction.
Agonists and antagonists
Acetylcholine, carbochol act as non-selective agonists. While atropine, oxybutynin act as a non-selective antagonist.
All the muscarinic receptors are G-protein coupled receptors.
They have minor differences among the mechanism of G-protein function, as mentioned above, for individual receptor types.