Sympathetic and Parasympathetic Receptors

Introduction

The autonomic nervous system (ANS) plays a crucial role in regulating various physiological functions in the human body. It consists of two main divisions: the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS). These systems work in opposition to each other to maintain homeostasis. The effects of the ANS are mediated through specific receptors called sympathetic and parasympathetic receptors.

Contents

Sympathetic Receptors

Sympathetic receptors, also known as adrenergic receptors, are activated by the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). These receptors are divided into two main types: α (alpha) and β (beta) receptors, each with their own subtypes.

Alpha (α) Receptors

Alpha receptors are further classified into two subtypes: α1 and α2 receptors.

Alpha-1 (α1) Receptors

α1 receptors are located in the smooth muscles of blood vessels, eyes, and genitourinary system. They are also found in the heart and central nervous system (CNS). Activation of α1 receptors leads to:

Vasoconstriction (narrowing of blood vessels)
Pupillary dilation (widening of the pupils)
Contraction of smooth muscles in the genitourinary system
Increased heart rate and force of contraction

Drugs acting on α1 receptors

Agonists: Phenylephrine, Methoxamine
Antagonists: Prazosin, Doxazosin, Tamsulosin

Alpha-2 (α2) Receptors

α2 receptors are located in the CNS, platelets, and prejunctional nerve terminals. Activation of α2 receptors leads to:

Inhibition of neurotransmitter release
Platelet aggregation
Decreased sympathetic outflow from the CNS

Drugs acting on α2 receptors

Agonists: Clonidine, Guanfacine, Dexmedetomidine
Antagonists: Yohimbine, Atipamezole

Beta (β) Receptors

Beta receptors are further classified into three subtypes: β1, β2, and β3 receptors.

Beta-1 (β1) Receptors

β1 receptors are primarily located in the heart. Activation of β1 receptors leads to:

Increased heart rate (positive chronotropic effect)
Increased force of contraction (positive inotropic effect)
Increased conduction velocity (positive dromotropic effect)

Drugs acting on β1 receptors

Agonists: Dobutamine, Xamoterol
Antagonists (beta blockers): Atenolol, Metoprolol, Bisoprolol

Beta-2 (β2) Receptors

β2 receptors are located in the smooth muscles of the bronchi, blood vessels, and uterus. Activation of β2 receptors leads to:

Bronchodilation (relaxation of bronchial smooth muscles)
Vasodilation (widening of blood vessels)
Relaxation of uterine smooth muscles

Drugs acting on β2 receptors

Agonists: Salbutamol (Albuterol), Salmeterol, Formoterol
Antagonists: Butoxamine, ICI-118,551

Beta-3 (β3) Receptors

β3 receptors are located in adipose tissue. Activation of β3 receptors leads to:

Lipolysis (breakdown of fat)
Thermogenesis (heat production)

Drugs acting on β3 receptors

Agonists: Mirabegron, Amibegron
Antagonists: SR 59230A

Parasympathetic Receptors

Parasympathetic receptors, also known as cholinergic receptors, are activated by the neurotransmitter acetylcholine (ACh). These receptors are divided into two main types: muscarinic (M) and nicotinic (N) receptors.

Muscarinic (M) Receptors

Muscarinic receptors are G protein-coupled receptors (GPCRs) and are further classified into five subtypes: M1, M2, M3, M4, and M5.

M1 Receptors

M1 receptors are primarily located in the CNS, gastric glands, and salivary glands. Activation of M1 receptors leads to:

Increased cognitive function
Increased gastric acid secretion
Increased salivary secretion

Drugs acting on M1 receptors

Agonists: Xanomeline, Cevimeline
Antagonists: Pirenzepine, Telenzepine

M2 Receptors

M2 receptors are located in the heart, smooth muscles, and CNS. Activation of M2 receptors leads to:

Decreased heart rate (negative chronotropic effect)
Decreased force of contraction (negative inotropic effect)
Decreased conduction velocity (negative dromotropic effect)
Smooth muscle relaxation

Drugs acting on M2 receptors

Agonists: Bethanechol, Carbachol
Antagonists: Methoctramine, AF-DX 116

M3 Receptors

M3 receptors are located in the smooth muscles of the gastrointestinal tract, urinary bladder, and eyes. Activation of M3 receptors leads to:

Increased gastrointestinal motility
Contraction of the urinary bladder
Pupillary constriction (narrowing of the pupils)

Drugs acting on M3 receptors

Agonists: Pilocarpine, Carbachol
Antagonists: Darifenacin, Solifenacin

M4 and M5 Receptors

The functions of M4 and M5 receptors are not well understood, and they are primarily located in the CNS.

Nicotinic (N) Receptors

Nicotinic receptors are ligand-gated ion channels and are further classified into two subtypes: nicotinic acetylcholine receptors (nAChRs) and ganglionic nicotinic receptors.

Nicotinic Acetylcholine Receptors (nAChRs)

nAChRs are located in the neuromuscular junction and the CNS. Activation of nAChRs leads to:

Muscle contraction (at the neuromuscular junction)
Increased neurotransmitter release (in the CNS)

Drugs acting on nAChRs

Agonists: Nicotine, Varenicline, Cytisine
Antagonists: Tubocurarine, Pancuronium

Ganglionic Nicotinic Receptors

Ganglionic nicotinic receptors are located in the autonomic ganglia. Activation of these receptors leads to:

Increased sympathetic and parasympathetic outflow

Drugs acting on ganglionic nicotinic receptors

Agonists: Nicotine, Dimethylphenylpiperazinium (DMPP)
Antagonists: Mecamylamine, Trimethaphan

Dual Action Drugs

Some drugs act on both sympathetic and parasympathetic receptors, either as agonists or antagonists.

Epinephrine (Adrenaline)

Epinephrine is an endogenous catecholamine that acts as an agonist on both α and β receptors. Its effects depend on the dose and the type of receptors activated.

Norepinephrine (Noradrenaline)

Norepinephrine is another endogenous catecholamine that acts primarily on α receptors and, to a lesser extent, on β1 receptors.

Dopamine

Dopamine is an endogenous catecholamine that acts on dopamine receptors (D1-D5) and, at higher doses, on α and β receptors.

Atropine

Atropine is a muscarinic receptor antagonist that blocks the actions of acetylcholine on muscarinic receptors.

Clinical Implications

Understanding the functions and pharmacology of sympathetic and parasympathetic receptors is crucial for the management of various medical conditions. Some examples include:

Cardiovascular Diseases

Beta blockers (e.g., metoprolol, atenolol) are used to treat hypertension, angina, and arrhythmias by blocking the effects of norepinephrine and epinephrine on β1 receptors in the heart.
Alpha-1 receptor antagonists (e.g., prazosin, doxazosin) are used to treat hypertension and benign prostatic hyperplasia (BPH) by blocking the effects of norepinephrine on α1 receptors in blood vessels and the prostate.

Respiratory Diseases

Beta-2 receptor agonists (e.g., salbutamol, salmeterol) are used to treat asthma and chronic obstructive pulmonary disease (COPD) by inducing bronchodilation through activation of β2 receptors in the bronchial smooth muscles.
Muscarinic receptor antagonists (e.g., ipratropium, tiotropium) are used to treat COPD by blocking the effects of acetylcholine on muscarinic receptors in the bronchial smooth muscles, leading to bronchodilation.

Genitourinary Disorders

Muscarinic receptor antagonists (e.g., oxybutynin, tolterodine) are used to treat overactive bladder by blocking the effects of acetylcholine on M3 receptors in the urinary bladder, leading to decreased bladder contractions.
Alpha-1 receptor antagonists (e.g., tamsulosin, alfuzosin) are used to treat BPH by blocking the effects of norepinephrine on α1 receptors in the prostate, leading to relaxation of prostatic smooth muscles and improved urine flow.

Neurodegenerative Diseases

Cholinesterase inhibitors (e.g., donepezil, rivastigmine) are used to treat Alzheimer’s disease by increasing the availability of acetylcholine in the CNS, which activates muscarinic and nicotinic receptors and improves cognitive function.

Conclusion

Sympathetic and parasympathetic receptors play a vital role in regulating various physiological functions in the human body. Understanding the subtypes of these receptors and the drugs that act on them is essential for the effective management of a wide range of medical conditions. As research continues to uncover new insights into the functions and pharmacology of these receptors, novel therapeutic approaches may emerge, leading to improved patient outcomes and quality of life.

Table 1: Summary of Sympathetic Receptors

Receptor Type	Subtypes	Location	Effects of Activation	Agonists	Antagonists
Alpha (α)	α1	Smooth muscles (blood vessels, eyes, genitourinary system), heart, CNS	Vasoconstriction, pupillary dilation, increased heart rate and force of contraction	Phenylephrine, Methoxamine	Prazosin, Doxazosin, Tamsulosin
	α2	CNS, platelets, prejunctional nerve terminals	Inhibition of neurotransmitter release, platelet aggregation, decreased sympathetic outflow	Clonidine, Guanfacine, Dexmedetomidine	Yohimbine, Atipamezole
Beta (β)	β1	Heart	Increased heart rate, force of contraction, and conduction velocity	Dobutamine, Xamoterol	Atenolol, Metoprolol, Bisoprolol
	β2	Smooth muscles (bronchi, blood vessels, uterus)	Bronchodilation, vasodilation, relaxation of uterine smooth muscles	Salbutamol (Albuterol), Salmeterol, Formoterol	Butoxamine, ICI-118,551
	β3	Adipose tissue	Lipolysis, thermogenesis	Mirabegron, Amibegron	SR 59230A

Table 2: Summary of Parasympathetic Receptors

Receptor Type	Subtypes	Location	Effects of Activation	Agonists	Antagonists
Muscarinic (M)	M1	CNS, gastric glands, salivary glands	Increased cognitive function, gastric acid secretion, and salivary secretion	Xanomeline, Cevimeline	Pirenzepine, Telenzepine
	M2	Heart, smooth muscles, CNS	Decreased heart rate, force of contraction, and conduction velocity; smooth muscle relaxation	Bethanechol, Carbachol	Methoctramine, AF-DX 116
	M3	Smooth muscles (gastrointestinal tract, urinary bladder, eyes)	Increased gastrointestinal motility, contraction of the urinary bladder, pupillary constriction	Pilocarpine, Carbachol	Darifenacin, Solifenacin
	M4, M5	CNS	Not well understood	–	–
Nicotinic (N)	nAChRs	Neuromuscular junction, CNS	Muscle contraction, increased neurotransmitter release	Nicotine, Varenicline, Cytisine	Tubocurarine, Pancuronium
	Ganglionic	Autonomic ganglia	Increased sympathetic and parasympathetic outflow	Nicotine, DMPP	Mecamylamine, Trimethaphan

References

Brunton, L. L., Hilal-Dandan, R., & Knollmann, B. C. (Eds.). (2018). Goodman & Gilman’s: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education.
Katzung, B. G., & Trevor, A. J. (Eds.). (2018). Basic & Clinical Pharmacology (14th ed.). McGraw-Hill Education.
Rang, H. P., Ritter, J. M., Flower, R. J., & Henderson, G. (2019). Rang & Dale’s Pharmacology (9th ed.). Elsevier.
Whalen, K., Finkel, R., & Panavelil, T. A. (Eds.). (2019). Lippincott Illustrated Reviews: Pharmacology (7th ed.). Wolters Kluwer.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always seek the advice of a healthcare provider with any questions regarding a medical condition.