Category Archives: Cholinergic Receptors

Nicotinic M Receptors: The Beach is That Way

http://www.urbandictionary.com/define.php?term=which%20way%20to%20the%20beach

So, as you may have guessed, Nicotinic M (Nm) Receptors are famous for their role in skeletal muscle movement!  They are all over the motor end plates at the neuromuscular junctions of our skeletal muscles.  So they are in charge of receiving the signals, via acetylcholine binding, to depolarize and contract! Nm Receptors have had a long history of being messed with in different ways, and it’s pretty awesome.  But I digress…

These receptors are Ligand Gated Ion Channels.  Remember those?  If not, check out “Our Friends the Receptors” in the Basic Pharmacology section.  The coolest thing about this type of receptor is that ligands (like Acetylcholine, or ACh) bind to them directly.  That means there is no chain reaction that must occur (like the “second messengers” in GPCRs, think of that game called “Telephone“).  The receptor simply changes its shape, and certain ions are allowed to flow in or out.  Genius! But why is it so important to have this kind of receptor at the Neuromuscular Junction?

Ligand Gated Ion Channels are FAST.  We need these because muscles need to quickly depolarize and repolarize to maintain a contraction or get ready for the next contraction.

Drugs that affect these receptors at the neuromuscular junctions either enhance the amount of ACh available (cholinesterase inhibitors), compete with ACh for binding (nondepolarizing neuromuscular blockers), or block ACh completely (depolarizing neuromuscular blockers).

Receptors never cease to amaze me.  Humor me for a moment and watch your fingers type something.  Then imagine how fast those ion channels are receiving signals and getting to work.  Incredible!  Now imagine what would happen if all of them were suddenly blocked.  Besides how awful that would be, can you think of a good use for that trick?

Detailed view of a neuromuscular junction: 1. ...
Detailed view of a neuromuscular junction: 1. Presynaptic terminal 2. Sarcolemma 3. Synaptic vesicle 4. Nicotinic acetylcholine receptor 5. Mitochondrion (Photo credit: Wikipedia)

Muscarinic Receptors: Blood Vessels, Sweat*, and Tears**

Sit back and relax after a meal, recline and let your heart slow down, feel the warmth of your extremities…and secrete those fluids!

Ewwwwww…secretions!!  Diaphoresis, urination, vasodilation, lactation, and all kinds sweaty gooey things coming out and doing their thing!  In a very crude and stunted way, this is a main function of the parasympathetic nervous system. 

Muscarinic receptors are usually what we are talking about when we refer to anything “cholinergic”.  This is because their function works to balance the agonism of adrenergic (sympathomimetic!) receptors, thus allowing our body to essentially work “normally”.  So if you remember nothing else at all about muscarinic agonists (or “cholinergic drugs”), do remember the words REST and WET.  Now, to delve into more detail.  Woot!

There are 5 subtypes of muscarinic receptor, and they are all G Protein Coupled Receptors (if you don’t know what I’m talking about see “Our Friends the Receptors” in the basic pharmacology section).  Let’s make that easier and cut out the last two, because they are mostly in the CNS and the jury is still out on what exactly they do.  Actually, the jury is still out on almost every receptor type, but researchers have dedicated their work to studying them and make new discoveries every day!

Anyway, for our purposes there are 3 muscarinic subtypes: M1, M2, and M3.  I recommend remembering them as head, heart, and trunk.  While not entirely encompassing, it’s a start!

1.  M1:  Head.  These guys are in the CNS, on salivary glands, and surrounding your esophagus.  So they help regulate parasympathetic signals from the CNS, help to begin the digestive process (which starts with salivation!), signal the stomach to secrete digestive “juices”, and speed along signals to your organs.

2. M2:  Heart.  These are the important receptors that help regulate the conduction speed and contractile force of the atria in your heart.  They, too, are in the CNS and on the heart itself!  In the atria, they counter the effect of sympathetic stimulation by relaxing how hard those amazing atrial cardiomyocytes are pumping…Negative Inotropic! They also monitor signals from the CNS to ease up on the stimulation given to the AV node and slowing the conduction…Negative dromotropic!

3.  M3:  Trunk (and Eye…I know, this messes it up).  These guys are in the CNS, on the ciliary bodies in your eye (remember the little guys that control your pupil?), on your bronchioles, on your blood vessels, and all over your digestive system, from start to finish!  The most important thing to remember is that they help you digest by enhancing secretions from the salivary glands down to the colon.  Pretty amazing, huh?  In your lungs, they actually cause a bit of bronchoconstriction, which is why we have to be very careful using muscarinic agonists.  One of the coolest (IMHO) features of M3 receptors is how they affect the blood vessels.  I will nerd out on this in another post, so for now, just remember vasodilitation!  In the eyes, they cause myosis, or pupillary constriction.

Can you guess what the opthamologist drops in your eyes to make your pupils HUGE?

So there you go.  Secretions and rest (mostly). Here is a summary of what muscarinic receptors are in charge of:

1.  Secretions along the digestive tract

2. Reduced contractility and conduction of the atria

3. Vasodilitation

4. Myosis

5. Speeding along autonomic signals

6. Bronchoconstriction

There was a lot of information in this post!  I needed help too (one can only pack so much into the Rolodex), so I consulted the humongous bag of notes I have.  These notes came from two lecturers:

Robert Mouton at Concordia University, Austin, TX.  He is a cell biologist and incredible professor of pharmacology and physiology.

Dr. Sue Greenfield at Columbia University, New York, NY.  She is a nurse practitioner and PhD who has a vast clinical knowledge of drugs and has the amazing ability to put their use into simple terms!

*But…why didn’t we talk about sweat??  Well, as I was writing this, I realized that the simplest way to remember muscarinic drugs is by their parasympathetic activity.  So…diaphoresis is indeed a muscarinic activity, but it is modulated by the sympathetic nervous system.  I know, I know!!  It’s very complicated.  If I were you, I’d just remember that most things wet come from M receptors.

**But…why didn’t we talk about tears??  Lacrimation is one of those tricky things that happen via the CNS, more specifically the cranial nerves.  The “tear signal” from that good old cranial nerve VII is modulated by muscarinic receptors.  Again, don’t cry over it.  Just assume that wet is muscarinic and if you are very curious then look it up!

So I sacrificed complete accuracy for a good title.

Cholinergic Receptors: Sit Back and Relax!

Cholinergic receptors are part of the parasympathetic branch of the autonomic nervous system.  This branch is often referred to as “Rest and Digest”, and that’s all thanks to these cholinergic receptors!  They are named after their number one fan: the neurotransmitter Acetylcholine (ACh). Any drug that is a cholinergic agonist (often just called a “cholinergic”, although parasympathomimetic has a nice ring to it!) will mimic ACh, cause more ACh to be released, or prevent ACh from being cleared.

There are two main types of cholinergic receptor:  Muscarinic and Nicotinic.  We will get to the details of these later.  You may hear drugs called “muscarinic agonists” and the like.  Just know that this is referring to cholinergics of some sort.

There are a few important things to remember about cholinergic receptors:

1.  When activated, they are responsible for increasing secretions (like sweat, saliva, and digestive “juices”). Think WET.

2.  They work opposite, but in conjunction with,adrenergic receptors in the heart.  So when they are activated, they slow the heart rate and dilate the blood vessels.  To put it another way, adrenergics are the GAS, cholinergics are the BRAKES.  You never have them on at the same time, but you need both of them to get places!

3. Some of them are the receptors that receive the signal for muscle contractions at the neuromuscular junctions, among many other things!