29: Drug Action on Nicotinic Receptors Flashcards
Explain the process of ACh signaling.
ACh diffuses across the synaptic cleft and binds to cholinergic receptors on the postsynaptic membrane.
Name the two different types of cholinergic receptors.
Nicotinic receptors and muscarinic receptors.
Describe the characteristics of nicotinic receptors.
- respond to ACh and nicotine
- ionotropic ligand-gated ion channels
- excitatory
- fast synaptic transmission
- brain, autonomic ganglia, adrenal medulla, and neuromuscular junction
Describe the characteristics of muscarinic receptors.
- respond to ACh and muscarine
- metabotropic G-protein coupled receptors
- excitatory OR inhibitory
- slow metabolic response
- brain, heart, and smooth muscles
Rank the binding affinity to nicotinic receptors of ACh, nicotine, and muscarine.
Rank the binding affinity to muscarinic receptors of ACh, nicotine, and muscarine.
Describe signal transduction process of nicotinic receptors.
- form pores through the cell membrane of the post-ganglionic nerves by conformational change after activation by ACh or nicotine.
- Control influx of Na+, K+, or Ca2+ at synapses.
- Trigger membrane depolarization
- mediate the fast transmission of nerve impulses
Explain the structure of nicotinic receptors.
- 5 membrane domains
- 17 subunits
- 2 ligand binding sites must be occuplied to activate the receptor
What are the two subtypes of nicotinic receptors? Give examples.
Nn: neuronal type
* brain: (a7)5 or (a4)2(b2)3
* autonomic ganglia: (a3)2(b4)3
* adrenal medulla gland
Nm: muscular type
* neuromuscular junction in skeletal muscle: a1ga1b1e
Explain the difference of ACh binding sites for Nn and Nm nicotinic receptors.
Nn: neuronal type
* ACh binding sites at interface of a/b and a/a
Nm: muscular type
* ACh binding sites at interface of a/g and
a/e or a/d
Explain the physiological reaction of nicotinic receptor activation in the brain.
In brain - regulate neurotransmitter release from nerve terminals (neuronal development, learning and memory formation, and reward).
* synaptic excitation
Explain the physiological reaction of nicotinic receptor activation in the PNS (autonomic ganglia).
In PNS - transmit outgoing signal from the pre- to post-synaptic cells within the SNS and PNS.
* excitatory depolarization
Explain the physiological reaction of nicotinic receptor activation in the adrenal medulla.
In the adrenal medulla - release catecholamines (epinephrine and norepinephrine) into the bloodstream in preparation for fight/flight reactions.
* excitatory depolarization
Explain the physiological reaction of nicotinic receptor activation in the neuromuscular junction.
In the neuromuscular junction of skeletal muscle - primary receptors in muscle for motor nerve-muscle communication (for muscle contraction).
* excitatory depolarization
List the nicotinic receptor agonists.
- acetylcholine
- nicotine
- choline
- succinylcholine
- lobeline
- varenicline
- cytisine
What is the pharmacological use of nicotine?
A stimulatory alkaloid found in tabacco products that is often used for the relief of nicotine withdrawal symptoms and an aid to smoking cessation.
What is the pharmacological use of varenicline?
Partial agonist at nicotinic receptor Nn - aid for smoking cessation.
What is the pharmacological use of cytisine?
A strong agonist for the nicotinic receptor Nn - used for treatment of tobacco smoking cessation.
What is the pharmacological use of lobeline.
treatment in addictions
What is the pharmacological use of succinylcholine?
An agonist of muscular nicotinic Nm receptors as a depolarizing neuromuscular blocker - used as a short-term muscle relaxation agent in anesthesia and intensive care.
Name some nicotinic receptor antagonists: ganglionic blockers Nn.
- Hexamethonium
- Pentolinium
- Benzohexonium
- Pentamine
- Chlorisondamine
- Mecamylamine
- Pempidine
- Trimetaphan
Name some nicotinic receptor antagonists: neuromuscular blockers Nm.
- Rocuronium
- Rapacuronium
- Vecuronium
- Pancuronium
- Atracurium
- Doxacurium
- Cisatracurium
- Tubocurarine
Explain the function of the ganglionic blockers.
- block nicotinic receptors for outgoing signals to be transmitted from the presynaptic to the postsynaptic cells within the ganglia of the ANS.
- block both sympathetic (excitatory) and parasympathetic (inhibitory) stimulation of the heart.
- Nn receptor antagonist
Explain Hexamethonium’s drug action on nicotinic receptors.
Neuronal nicotinic receptor antagonist
* therapeutic indication: hypertension
