Neurotransmission and Drug Action in Synapse

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Questions and Answers

How does the activation of the sympathetic nervous system affect heart rate and force of contraction?

It increases both the rate and force of contraction of the heart.

What roles do the G-alpha subtypes Gi, Gs, and Gq play in GPCR signaling?

Gi decreases cAMP levels, Gs increases cAMP levels, and Gq activates phospholipase C.

Explain the effects of cholinergic synapses on the cardiovascular system.

Cholinergic synapses decrease heart rate and force of contraction, primarily through parasympathetic actions.

What pharmacological effect do β-blockers have on the heart?

β-blockers decrease heart rate and force of contraction by blocking β-adrenergic receptors. Signup and view all the answers

Describe how sympathetic and parasympathetic stimulation affects the eye.

Sympathetic stimulation dilates the pupil, while parasympathetic stimulation constricts the pupil and contracts the ciliary muscle. Signup and view all the answers

What is the primary neurotransmitter of the peripheral nervous system (PNS) and its significance?

Acetylcholine (ACh) is the primary neurotransmitter of the PNS, crucial for neuromuscular transmission and autonomic functions. Signup and view all the answers

Describe the process of acetylcholine biosynthesis.

Acetylcholine is synthesized in the presynaptic terminal from choline and acetyl CoA. Signup and view all the answers

Explain the role of norepinephrine in the sympathetic nervous system and its mechanisms of action.

Norepinephrine (NA) acts as the neurotransmitter at post-ganglionic sympathetic neurons, stimulating adrenergic receptors to mediate physiological responses. Signup and view all the answers

What impact does amphetamine have on norepinephrine signaling?

Amphetamine increases norepinephrine signaling by blocking its reuptake, leading to prolonged stimulation of post-synaptic neurons. Signup and view all the answers

Differentiate between nicotinic and muscarinic receptors in terms of their type and function.

Nicotinic receptors are ligand-gated ion channels involved in fast synaptic transmission, while muscarinic receptors are G-protein coupled receptors linked to slower signal transduction implications. Signup and view all the answers

What are cholinergic neurons responsible for secreting?

Cholinergic neurons secrete acetylcholine (ACh). Signup and view all the answers

What is the role of muscarinic antagonists?

Muscarinic antagonists block the action of acetylcholine at muscarinic receptors. Signup and view all the answers

Describe the effect of muscarine on heart rate.

Muscarine slows down the heart rate. Signup and view all the answers

What does the term 'mimetic' refer to in pharmacology?

'Mimetic' refers to substances that mimic or promote the action of specific neurotransmitters. Signup and view all the answers

Explain the action of nicotine at the neuromuscular junction.

Nicotine stimulates contraction of skeletal muscles at the neuromuscular junction. Signup and view all the answers

What is the primary mechanism of action of curare?

Curare blocks the actions of nicotine at the neuromuscular junction. Signup and view all the answers

What is the impact of tetanus toxin on synaptic function?

Tetanus toxin prevents the fusion of vesicles with the presynaptic membrane, increasing muscle contraction. Signup and view all the answers

How does nerve gas such as Sarin affect muscle contraction?

Sarin inhibits acetylcholinesterase, resulting in uncontrolled muscle contraction. Signup and view all the answers

What does the term 'lytic' indicate in pharmacological terminology?

'Lytic' indicates the inhibition or termination of the action of neurotransmitters. Signup and view all the answers

What are the historical contributions of 1905 in the study of ACh?

In 1905, nicotine and curare were identified for their actions at the neuromuscular junction. Signup and view all the answers

Study Notes

Pharmacological Agents and Drugs Acting on Synapses

Drugs and pharmacological agents act on synapses in the nervous system, affecting neurotransmission
The peripheral nervous system (PNS) is the focus of study, with its key neurotransmitters being acetylcholine (ACh) and noradrenaline (NA)

Neuromodulation of Synaptic Transmission

The nervous system is divided into the central nervous system (CNS) and the PNS
The PNS is further divided into the somatic nervous system and the autonomic nervous system
The autonomic nervous system is then divided into the sympathetic and parasympathetic nervous systems
Acetylcholine (ACh) is the main neurotransmitter in somatic nerves and pre-ganglionic fibres of the autonomic nervous system, along with post-ganglionic fibres in the parasympathetic nervous system
Noradrenaline (NA) is the neurotransmitter in post-ganglionic fibres of the sympathetic nervous system

Acetylcholine (ACh)

ACh is the key neurotransmitter in the peripheral nervous system, first identified by Dale in 1930
ACh acts at neuromuscular junctions, all preganglionic fibres and postganglionic fibers of the parasympathetic nervous system
ACh is synthesized in the presynaptic terminal from choline and acetyl-CoA
ACh's action is terminated by its degradation by acetylcholinesterase
1921, Otto Loewi discovered the release of a chemical messenger (Vagusstoff) from the vagus nerve impacting heart rate

Pharmacology of the ACh Synapse

1921 Loewi's showed stimulation of vagus causes heart slowing via release of a substance he named Vagusstoff
Acetylcholine (ACh) acts on two types of receptors: Nicotinic and Muscarinic
- Nicotinic receptors are ionotropic receptors, ligand-gated ion channels found in autonomic ganglia and neuromuscular junctions.
- Muscarinic receptors are metabotropic receptors, G-protein coupled receptors found in parasympathetic synapses with target organs like smooth muscle and cardiac muscle

Acetylcholine (ACh) Biosynthesis

ACh is synthesized from choline and acetyl-CoA in the presynaptic terminal

Noradrenaline (NA)

Noradrenaline (NA) is the main neurotransmitter at post-ganglionic sympathetic neurons.
NA is a catecholamine synthesized from tyrosine, with its action terminated by reuptake into the presynaptic terminal
NA receptors are of two major subtypes: alpha-adrenergic receptors and beta-adrenergic receptors. These receptors use cAMP as a second messenger.
The drug amphetamine affects NA synapses by blocking reuptake

Noradrenergic Synapse

Amphetamine blocks NA reuptake, increasing prolonged NA stimulation of postsynaptic neurons

Cholinergic Synapses

Cholinergic synapses use ACh for transmission
Two types:
- Ionotropic receptor (nicotinic) - ligand-gated ion channels responsible for muscle contraction.
- Metabotropic receptor (muscarinic) - G-protein coupled receptors affecting target organs like smooth muscle and cardiac muscle.

The Nicotinic Receptor

The alpha subunit of the nicotinic ACh receptor has four transmembrane domains (M1, M2, M3, M4) with extramembrane sequences above and below

The Cholinergic Synapse ((i) e.g. NMJ and (ii) Atrial cells parasympathetic)

The cholinergic synapse process of NMJ and atrial cells including ACh release, receptor binding, and subsequent depolarization/hyperpolarization and effects
Different types of ACh receptors (ionotropic and metabotropic) have differing signalling pathways

G Protein-Coupled Receptor (GPCR) Signaling

Ligand binding triggers G-protein activation
Activated G-protein activates or inhibits downstream effectors(enzymes) like adenylate cyclase or phospholipase C, creating cascades of intracellular responses.

G-alpha Subunit of GPCRs

G-alpha subunits (αs, Gi, Gq/11/12/13) are crucial for diversity in GPCR function, influencing different cellular processes.
They differentially affect downstream targets, like ion channels or enzymes

GPCR Signaling Pathways

GPCR signaling interacts with other signalling pathways, like those from hormones and growth factors.

Pharmacological Modulation of Cholinergic Synapses in the PNS

Drugs affecting these synapses include agonists that mimic ACh effects and antagonists that block them.

Effects of Autonomic Stimulation

Table providing sympathetic and parasympathetic effects on various organs (eye, heart, arterioles, lungs, gut, liver, and bladder)

Effect of β-blockers

Graph showing the effect of the beta-blocker drug oxprenolol on heart rate.

Terminology

Definitions for terms related to cholinergic neurotransmission, like cholinergic, cholinoceptor, muscarinic antagonist, mimetic (agonist), and lytic.

Pharmacology of the ACh Synapse: A Historical Prospective

Details about historical discoveries of ACh synapse's function

Targets for drug action at the cholinergic synapse

Detail about types of drugs that interact with different parts of the cholinergic synapse (pre-synaptic, synaptic, and post-synaptic inhibitors) and examples.

Muscarinic Receptor Subtypes

Description of 5 different types of Muscarinic receptors (M1 to M5) with their main location, functions and activation pathways.

Diversity of Muscarinic Receptor function

Description of different G proteins interacting with each subtype of muscarinic receptor

Drugs acting at Muscarinic Receptors

Description of drugs stimulating muscarinic receptors (parasympathomimetics) and inhibiting muscarinic receptors (parasympatholytics)

Drugs acting at Muscarinic Receptors Tables

Tables providing information about drug structures, receptor specificity, hydrolysis by AChE, and clinical uses

Effects of Muscarinic Agonists

Details about effects of muscarinic agonists, including cardiovascular effects, smooth muscle effects, gland effects, and central effects.

Clinical Use of Muscarinic Agonists and Antagonists

Main uses of muscarinic agonists (e.g., glaucoma treatment) and antagonists (e.g., topical treatment for pupil dilation)

Nice and easy way to remember!

Diagram summarising different subtypes of muscarinic receptors, location of the subtypes, and related agonists and antagonists.

Overview of neurotransmitters in the PNS

Diagram showing the pathways of different neurotransmitters (ACh, NA, adrenaline/epinephrine) in the peripheral nervous system.

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Description

Test your knowledge on the sympathetic and parasympathetic nervous systems, including the effects of neurotransmitters, GPCR signaling, and pharmacological agents like β-blockers. This quiz covers various aspects of neurotransmission, including receptor types and the impact of drugs on cardiovascular function.