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Neurotransmission in the
Autonomic Nervous System
(ANS)
Basic principles
Tibor Zelles
Dept. Pharmacology & Pharmacotherapy
Semmelweis University
9-25-2018
Evaluation only.
Created with Aspose.PowerPoint.
Copyright 2004 Aspose Pty Ltd.
Cell communication
Cell Signalling Biology - Michael J. Berridge - http://csb.portlandpresspublishing.com - 2019
Hierarchical neuronal systems:
- pathways of sensori perception & motor control – phasic actions
- synaptic contact
- myelinated axons (50 m/s)
- relay/projection neurons – Glu
- local circuit neurons (interneurons) - GABA/Gly
Nonspecific / Diffuse neuronal systems:
- sleeping-waking, attention, emotional states, appetite – tonic actions
- non-synaptic ‚contact’
- unmyelinated axons (0.5 m/s)
- monoamine transmitters (e.g. NA, DA, 5-HT)
Cellular organization of the brain
Hierarchical neuronal systems in the CNS
BG Katzung, 12th Ed.
Projection /
(interneurons)
BG Katzung, 13th Ed.
Diffuse neurotransmitter pathways in the CNSlargely modulate the function of the hierarchical pathways
Other similar systems (e.g. histamine & orexin)
Implicated in global
functions:
• Sleeping
• Waking
• Attention
• Appetite
• Emotional state
Basic steps in neurochemical transmission
• Synthesis
• Storage
• Release
• Reception/recognition
• Termination
• resides in the presynaptic terminal
• can be released
• synaptic mimicry:
- addition of the substance produces the same
effect as nerve stimulation
- antagonist blocks the response
Criteria for neurotransmitters
Steps involved in excitatory and inhibitory
neurotransmission
Goodman & Gilman’s, 12th Ed.
Types of neurotransmitters & neuromodulators
Rang & Dales’s, 8th Ed.
• Sympathetic
• Parasympathetic
• Enteric
The 3 divisions of the
Autonomic Nervous System (ANS)
ACh & NA as transmitters in the peripheral
nervous system
C, cervical; GI, gastrointestinal; L, lumbar; M, medullary; S, sacral; T, thoracic.
The autonomic nervous system (ANS)
The ANS in more detail
(only for home consumption for gourmets)
Goodman & Gilman’s, 12th Ed.
EPSPs and IPSPs in an autonomic ganglion cell
M2→ G → IK
M1 → Gq → PLC → [Ca2+]i → IK,Ca ↓
BG Katzung, 12th Ed.
The intestinal wall & the enteric nervous system (ENS)
EPAN/IPAN – Extrinsic/Intrinsic Primary Afferent Neuron; EN/IN – Excitatory/Inhibitory Neuron; EC – Entrochromaffin Cell;
SC/AC – Secretory/Absorptive Cell; NP - Neuropeptide BG Katzung, 12th Ed.
BG Katzung, 12th Ed.
BG Katzung, 12th Ed.
→ Aqueous humor secretion (Glaucoma)
β-blockers
BG Katzung, 12th Ed.
-agonists
M-antagonistsmydriasis
(eye
examination)
M-antagonists → cycloplegia (Uveitis; eye examination)
The logic of therapy in ANS pharmacology
(examples)
M-antagonists used for:
• Asthma bronchiale, COPD
The logic of therapy in ANS pharmacology
(examples)
• Urinary incontinence
• (Urinary retention – side effect)
BGKatzung, 9E
The logic of unwanted effects based on ANS
pharmacology - neuromuscular blocking drugs
nAChR inhibition in ganglia
Histamine release
BP
Bronchospasm
Cardiac mAChR inhibition
(increase of NA release, too)
Tachycardia
Cholinergic
junction
BG Katzung, 12th Ed.
LTX
+
-+ /pH
~5
.5
Mechanism of action of BTx
BoNT
motor neuron
ACh release
TeTx
Renshaw cell
Gly release
spastic paralysisflaccid paralysis
-
-+ /pH
~5
.5
MAO
Periferal DOPA
decarboxylase inhibitors[anti-Parkinson]
-MAO-A/BIs
-
COMTIs
COMT
Indirectly acting
sympathomimetics
α-methyl-DOPA
l-DOPA = levodopa[anti-Parkinson]
NA-ergic
junction
[anti-pheochromocytoma]
[antihypertensive]
[anti-Parkinson]
[antidepressant/anti-Parkinson]
[antihypertensive]
[nasal decongestants,
psychostimulants]
[antihypertensive]
[antihypertensive 2 agonists]
BG Katzung, 12th Ed.
Synthesis of DA, NA and A
Periferal DOPA
decarboxylase inhibitors
Metyrosine
α-methyl-DOPA
α-methyl-NA
-
-
Goodman & Gilman’s, 12th Ed.
Metabolism of catecholamines by catechol-O-
methyltransferase (COMT) & monoamine oxidase
(MAO)
BG Katzung, 12th Ed.
Types of ion channels and neurotransmitter
receptors in the nervous system
BG Katzung, 13th Ed.
Structure of nAChRs - ionotropic
mAChRs – metabotropic (mACh1,3,5 stimulatory,
mACh2,4 inhibitory)
Structure of and β adrenergic receptors -
metabotropic
Goodman & Gilman’s, 12th Ed.
Neuromodulation & co-transmission
[A] Postulated homotropic and heterotropic interactions between sympathetic and parasympathetic nerves. [B] Some of the known inhibitory and facilitatory influences on noradrenaline release from
sympathetic nerve endings. 5-HT, 5-hydroxytryptamine; A, adrenaline; ACh, acetylcholine; NA, noradrenaline; NO, nitric oxide; PG, prostaglandin; PGE, prostaglandin E.
Presynaptic regulation of transmitter release from
noradrenergic and cholinergic nerve terminals
Presynaptic inhibition
[A] Inhibitory effect of A on ACh release from postganglionic
parasympathetic nerves in the guinea pig ileum.
[B] NA release from mouse hippocampal slices in response
to trains of electrical stimuli
(α2 KO)
1, Uptake of precursors; 2, synthesis of transmitter; 3, uptake/transport of transmitter into vesicles; 4, degradation of surplus transmitter; 5, depolarisation by propagated action potential; 6, influx of
Ca2+ in response to depolarisation; 7, release of transmitter by exocytosis; 8, diffusion to postsynaptic membrane; 9, interaction with postsynaptic receptors; 10, inactivation of transmitter; 11,
reuptake of transmitter or degradation products by nerve terminals; 12, uptake of transmitter by non-neuronal cells; and 13, interaction with presynaptic receptors. The transporters (11 and 12) can
release transmitter under certain conditions by working in reverse. These processes are well characterised for many transmitters (e.g. acetylcholine, monoamines, amino acids, ATP). Peptide
mediators (see Ch. 19) differ in that they may be synthesised and packaged in the cell body rather than the terminals.
Basic steps in neurochemical transmission
sites of drug action
• Synthesis
• Storage
• Release
• Reception/recognition
• Termination
Goodman & Gilman’s, 12th Ed.
Goodman & Gilman’s, 12th Ed.
Goodman & Gilman’s, 12th Ed.
Thanks for your
attention
