Lecture 7 - Principles Of Chemical Transmission Flashcards
What are the 3 main types of chemical communication?
Endocrine (hormone) - insulin, adrenaline Paracrine (local hormone) - histamine, prostaglandin Neurotransmitters - acetylcholine, noradrenaline
What does the autonomic system consist of?
Sympathetic, parasympathetic and ENS
What does the autonomic system convey?
All the outputs from the CNS to the rest of body
What is the autonomic system outside of influence of?
Voluntary control
What are the main processes autonomic system regulates?
Contraction and relaxation of vascular and visceral smooth muscle All doctrine and certain endocrine secretions The heartbeat Energy metabolism (liver and skeletal muscle)
Otto Loewi and Vagustoff
One heart was connected to the vagus nerve Heart 1 was placed in a chamber that contained heart 2 Fluid from chamber heart 1 was allowed to flow into chamber heart 2. Electrical stimulation of the vagus nerve caused heart 1 to slow down Hypothesis: electrical stimulation of the vagus nerve released a chemical into fluid of chamber 1 that flowed into chamber 2
What are the criteria for the identification of a neurotransmitter?
The chemical must be produced within a neuron The chemical must be found within a neuron When a neuron is stimulated (depolarised) a neuron must release the chemical When a chemical is released, it must act on post-synaptic receptor and cause a biological effect
After a chemical is released, it must be inactivated. Inactivation can be through a reuptake mechanism or by enzyme that stops the action of chemical
What are efferent nerves?
Nerve that come out of the central nervous system
Parasympathetic
Long preganglionic fibres and short post ganglionic fibres
Sympathetic
Short preganglionic fibres and long post ganglionic fibres
What is ACH a neurotransmitter of?
Both parasympathetic and sympathetic branches of nervous system
Where does the difference and the ability to manipulate branches of ANS come between?
Post ganglionic fibre and target organs
What are the receptors for Adrenal Medulla and somatic in nature?
Nicotinic
Where are nicotinic receptors found in ANS?
Between pre and post ganglionic fibres
What are the target organ for parasympathetic fibres?
Muscarinic receptors
In sympathetic what is released?
Noradrenaline Adrenoceptor (alpha/beta)
What are the steps in neurotransmissiom?
- Uptake of precursors 2. Synthesis of neurotransmitter 3. Storage of neurotransmitter 4. Breakdown of surplus transmitter 5. Depolarisation by a propagated action potential 6. Influx of calcium in response to depolarisation 7. Release of transmitter by exocytosis 8. Diffusion to postsynaptic membrane 9. Interaction with postsynaptic membrane 10. Inactivation of transmitter 11. Reuptake of transmitter or degradation productions by nerve terminals 12. Uptake of transmitter by non-neuronal cells 13. Interaction with presunaptic receptors
What can presynaptic modulation of transmitter release be?
Heterotrophic or homotropic
What are the 2 presynaptic terminals?
Cholinergic and adrenergic
Heterotropic
A neurotransmitter is affecting the release of another neurotransmitter from a distinct remote site Noradrnergic neuron synapsid on a cholinergic neuron or neuron collateral synapsing on noradrenergic terminal
What does noradrenaline release have a negative regulatory effect upon?
ACH release
Homotropic
The neurotransmitter feeds back on the site on which it has been released Noradrenaline is released into synaptic cleft Noradrenaline also feed back via relevant noradrenergic receptors located presynaptically to damp down its own release (negative modulators effect)
Noradrenaline
Postganglionic sympathetic nerve endings Series of varicosities Acts on alpha and beta adrenoceptors
What are the current classification of noradrenaline?
Alpha 1 activates phospholipase C Alpha 2 inhibit adenylate cyclase Beta 1,2,3 stimulate adenylate cyclase
What is the synthesis and release of NA?
Stored in vesicles Presynaptic mechanism for regulation of NA release Action terminated by reuptake Subsequent metabolism: monoamine oxidase or catechol-O-methyl transferase
What enzyme is required to convert trypsin into DOPA?
Tryosine hydroxylase
What enzyme is required to convert DOPA to dopamine ?
DOPA decarboxylase
What enzyme is required to convert Dopamine into Noradrenaline ?
Dopamine B-hydroxylase
What enzyme is required to convert noradrenaline into adrenaline?
Phenylethanolamine N-methyltransferase
What is smooth muscle contraction mediated by?
Alpha1-adrenoceptor
What is smooth muscle relaxation mediated by?
Beta2-adrenoceptor
What is cardiac muscle ?
Ionotropic and chronotropic effect Mediated by: beta1-adrenoceptor
What is carbohydrate metabolism mainly mediated by?
Beta-1 adrenoceptor
What is lipid metabolism mediated by?
Beta3 adrenoceptor
What are nerve terminals mediated by?
Alpha2-adrenoceptor. Effect us inhibitory Basis of action of the antihypertensive clonidine
What are B-adrenoceptor antagonist main uses?
Cardiovascular disease
Synthesis of NA
Alpha-methyl-tyrosine
Reserpine
Blocks noradrenaline accumulation in vesicles Depleted NA store Effective in hypertension but may cause severe depression
How do you interfere with pre-synaptic release modulation?
Alpha 2 selective agonist
What are the 2 different types of activity of exogenous ACH Dale established?
Muscarinic - parasympathetic stimulation Nicotinic - stimulation of autonomic ganglia
What are muscarinic receptors?
G protein coupled receptors and 5 molecular subtypes known Either activate phospholipase C or inhibit adenylate cyclase
What are the different receptors of muscarinic?
M1 receptors (neural) M2 receptors (cardiac) M3 receptors (glandular/smooth muscle)
What are effects of muscarinic agonist (parasympathetic activation)?
Bradycardia Vasodilation Smooth muscle contraction Sweating Salivation
What are peripheral actions mainly mediated by?
Action on M2 and M3 receptors
What are the clinical use of muscarinic agonist?
Glaucoma and GI hypotonia
What are Muscarinic Antagonist referred to as?
Parasympathytics
What are the main peripheral effects of Muscarinic Antagonist?
Inhibition of secretion Tachycardia Mydriasis Smooth muscle relaxation Inhibition of gastric acid secretion Excitatory effect on CNS
Neuromuscular
Blepharospasm Spasticity Facial wrinkles Pain conditions (headache and musculoskeletal)
Autonomic
Sialorrhea Hyperhidrosis Urological disorder Gastrointestinal disorders
What is used In myasthenia gravis?
Neostigmine and physostigmine
