May 05, 2015

Autonomic Receptors and Post-Receptor Mechanisms of Action

The autonomic nervous system regulates many of the internal organs through a balance of two aspects, or divisions. Along with the endocrine system, the autonomic nervous system is instrumental in homeostatic mechanisms in the body. The two divisions of the autonomic nervous system are the sympathetic division and the parasympathetic division. The sympathetic system is associated with the fight-or-flight response, and parasympathetic activity is referred to by the epithet of rest and digest. Homeostasis is the balance between the two systems. Most organs in the body are innervated by both divisions and usually they have antagonistic effects. For example, the heart receives connections from both the sympathetic and parasympathetic divisions. One causes heart rate to increase, whereas the other causes heart rate to decrease.

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This is a Question & Answer revision article designed for medical students and professionals preparing for the PLAB, MRCP or USMLE examinations. They are based on actual questions from these examinations. You may find more useful one of our many articles on Diseases & Conditions, Medical Syndromes, Health & Wellness or Home Remedies.
In this article:
Chemical signaling in the autonomic nervous system
MCQ exam: clinical scenario
MCQ exam: answer
MCQ exam: explanation

Chemical signaling in the autonomic nervous system

Where an autonomic neuron connects with a target, there is a synapse. The electrical signal of the action potential causes the release of a signaling molecule, which will bind to receptor proteins on the target cell. Synapses of the autonomic system are classified as either cholinergic, meaning that acetylcholine (ACh) is released, or adrenergic, meaning that norepinephrine is released. The terms cholinergic and adrenergic refer not only to the signaling molecule that is released but also to the class of receptors that each binds.

The cholinergic system includes two classes of receptor: the nicotinic receptor and the muscarinic receptor. Both receptor types bind to ACh and cause changes in the target cell. The nicotinic receptor is a ligand-gated cation channel, and when stimulated, always has an excitatory effect on the cell. The muscarinic receptor is a G protein–coupled receptor. There are several different muscarinic receptors in the body, some receptors are excitatory and some are inhibitory. The nicotinic and muscarinic receptors are named for, and differentiated by, other molecules that bind to them. Whereas nicotine will bind to the nicotinic receptor, and muscarine will bind to the muscarinic receptor, there is no cross-reactivity between the receptors. The situation is similar to locks and keys. Imagine two locks—one for a classroom and the other for an office—that are opened by two separate keys. The classroom key will not open the office door and the office key will not open the classroom door. This is similar to the specificity of nicotine and muscarine for their receptors. However, a master key can open multiple locks, such as a master key for the Biology Department that opens both the classroom and the office doors. This is similar to ACh that binds to both types of receptors. The molecules that define these receptors are not crucial—they are simply tools for researchers to use in the laboratory. These molecules are exogenous, meaning that they are made outside of the human body, so a researcher can use them without any confounding endogenous results (results caused by the molecules produced in the body).

The adrenergic system also has two classes of receptors, named the alpha (α)-adrenergic receptor and beta (β)-adrenergic receptor. Unlike cholinergic receptors, these receptor types are not classified by which drugs can bind to them. All of them are G protein–coupled receptors. There are two types of α-adrenergic receptors, termed α1 and α2, and there are three types of β-adrenergic receptors, termed β1, β2 and β3.

MCQ exam: clinical scenario

Concerning receptors and their mechanisms of action. The main autonomic receptor types and post-receptor mechanism may vary from one tissue to another.

Select the correct match of receptor / tissue / postreceptor mechanism for the following tissues:

a) M2 / heart / opening of ligand-gated calcium channels
b) Nm / skeletal muscle endplate / increased IP3 and diacylglycerol
c) Alpha-2 / smooth muscle and glands / decrease of cAMP
d) Beta-2 / smooth muscle / increased cAMP
e) Dopamine-1 / smooth muscle / increased IP3 and diacylglycerol

MCQ questions & answers on medicalnotes.info

MCQ exam: answer

The correct answer is D.

MCQ exam: explanation

M2 is found in the heart. But it does not work via ligand gated calcium channels. It works through the Gq protein leading to the pathway of IP3 and diacylglycerol.

Nm is found in skeletal muscle endplate. But it does not work via increased IP3 and diacylglycerol. It’s a ligand gated calcium channel.

Alpha-2 is not found in smooth muscles and glands. It works by inhibiting AMP cyclase via Gi protein.

Dopamine-1 is found in smooth muscles. But it works on Gs proteins, thus increasing cAMP instead of increasing IP3 and diacylglycerol. That leaves us with one answer, which is D.

Beta-2 is found in smooth muscles. It works on the Gs protein, increasing the cAMP levels

Reference(s)
1). Lumen: Module 13: The Autonomic Nervous System. Available online: https://courses.lumenlearning.com/austincc-ap1/chapter/divisions-of-the-autonomic-nervous-system/

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