Membranes and Receptors - Autonomic Nervous System

Study Notes

Membranes and Receptors - The Autonomic Nervous System

The autonomic nervous system involves G-protein coupled receptors (GPCR) and ligand-gated channels.
Adrenergic receptors (α and β) and muscarinic receptors (M) are typically GPCRs.
Nicotinic receptors (N1 and N2) are ligand-gated channels.
Even-numbered adrenergic and muscarinic receptor subtypes tend to be inhibitory, while odd-numbered tend to be excitatory.
Nicotinic receptors are always excitatory.
Cholinergic receptors (cholinoceptors) include nicotinic and muscarinic receptors.
Nicotinic receptors are found in autonomic ganglia (sympathetic and parasympathetic) and neuromuscular junctions (somatic).
Muscarinic receptors are found on non-innervated blood vessels and post-ganglionic cholinergic endings in sympathetic nerves to sweat glands, and parasympathetic nerves to effector organs (e.g., cardiovascular system, respiratory system, eye, genitourinary tract, glands).
Cholinergic receptors are differentiated by their preferential activation by alkaloids like nicotine (from tobacco) and muscarine (from certain poisonous mushrooms).
Adrenergic receptors have subtypes α1, α2, β1, β2, and β3.
Each receptor subtype has different locations and functions in various tissues (e.g., heart, blood vessels, lungs, etc.).
The actions of agonists on adrenergic receptors vary.
Drugs can influence neurotransmission through various mechanisms, such as acting on cholinoceptors or affecting the enzymes involved in neurotransmitter degradation and synthesis.
Major drug classes used to manipulate autonomic function relate to cholinergic and adrenergic receptors.
These include nicotinic cholinoceptor antagonists, muscarinic cholinoceptor agonists, muscarinic cholinoceptor antagonists, and cholinesterase inhibitors.
Specific drugs have specific uses, including treatment of glaucoma, myasthenia gravis , COPD, etc.

Drugs Acting on Cholinergic Nerve Terminals

Nicotinic cholinoceptor antagonists (e.g., Tubocurarine, pancuronium) cause muscle paralysis during anesthesia.
Muscarinic cholinoceptor agonists (e.g., Pilocarpine) treat glaucoma.
Muscarinic cholinoceptor antagonists (e.g., Hyoscine butylbromide, Ipratropium bromide) treat bronchoconstriction in asthmatics.
Cholinesterase inhibitors (e.g., Neostigmine, pyridostigmine) treat myasthenia gravis..

Drugs Acting on Adrenergic Receptors

Selective β1 agonists (e.g., Dobutamine) treat heart failure.
Selective β2 agonists (e.g., Salbutamol, terbutaline) treat bronchoconstriction.
Selective α2 agonists (e.g., Clonidine) treat hypertension.
α-Antagonists (e.g., Phentolamine) treat peripheral vascular diseases.
Selective β-antagonists (e.g., Propranolol) treat hypertension and angina.

Clinically Relevant Drugs (Various categories)

Various drugs (e.g., a-methyl-tyrosine, Carbidopa, guanethidine, and bretylium) affect norepinephrine synthesis, release or uptake in the synaptic cleft.
Indirectly acting sympathomimetics (e.g., tyramine, amphetamines) are structurally related to norepinephrine but exert their effects via alternative methods.
Uptake 1 inhibitors (e.g., tricyclic antidepressants like amitriptyline) affect noradrenaline mechanisms.

Summary

Understanding the specific types of receptors and their related physiological functions are crucial for recognizing the role of drugs manipulating the autonomic nervous system.