Membranes and Receptors - Autonomic Nervous System

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.