Discuss the role and general mechanism of action of CNS neurotransmitters
Role: cause excitation of of postsynaptic cells by depolarising or hyperpolarising the postsynaptic membrane
General mechanism: neurotransmitter interacts with postsynaptic membrane > rapid, temporary opening of ion channels > ions diffuse through the postsynaptic membrane according to their ion concentration gradients > change in the postsynaptic membrane potential (de- or hyperpolarises depending on the direction of the ions)
Describe distribution concerning neurotransmitters (Ach)
Distributed throughout the CNS; high concentrations in the cerebral cortex, thalamus, basal nuclei, and hippocampus
Describe synthesis and clearance (disposal) concerning neurotransmitters (Ach)
Synthesis occurs in nerve endings. After release, Ach is rapidly hydrolysed by acetylcholinesterase into choline and acetate
Describe the degradation enzymes concerning neurotransmitters ( Ach)
Acetylcholinesterase
Describe receptors regarding neurotransmitters (Ach)
Cholinergic receptors which are subdivided into nicotinic and muscarinic receptors
Describe intracellular (postsynaptic) effects (actions/functions) regarding neurotransmitters (Ach)
Somatic (nicotinic ) Autonomic ganglia (nicotinic) Adrenal medulla (nicotinic)
Myasthenia gravis: auto-immune nicotinic receptor dysfunction at skeletal muscle NMJ (treat w/ acetylcholinesterase inhibitors)
Parkinson’s disease: dopamine- Ach imbalance (relative Ach excess). Treat w/ laevo- DOPA
Describe distribution of NA
At most sympathetic postganglionic endings
Describe the synthesis and clearance (disposal) of NA
Secreted by adrenal medulla formed by tyrosine hydroxylation and decarboxylation. Some tyrosine formed from phenylalanine, but most from dietary origin.
NA removed from the synaptic cleft by binding to postsynaptic receptors or presynaptic receptors, reuptake into presynaptic neurons or catabolism
Describe the degradation enzyme of NA
MAO (on the outside surface of mitochondria by oxidation) and COMT ( methylation)
Describe the receptors of NA
Alpha receptors: prevalent in vascular system
alpha 1a, alpha 1b, and alpha 1d increase IP3 and DAG
alpha 2a, alpha 2b, and alpha 2c decrease cAMP
Beta receptors: prevalent in cardio-respiratory system ( and involved in nutrient metabolism)
beta 1, beta 2, and beta 3 increase cAMP
Describe the intracellular (postsynaptic) effects (actions/functions) of NA
Effects of alpha and beta adrenergic receptor stimulation - autonomic sympathetic postganglionic target organs; also CNS and metabolic effects
Central effects - stimulation of RAS and wakefulness, aggression and nutrition. NA deficiency leads to depression
Describe the distribution of dopamine
In the sympathetic ganglia, hypothalamus, limbic system, neocortex, and retina
Describe the synthesis and and clearance of dopamine
Synthesis: intermediate in NA synthesis
Clearance: active reuptake
Describe the degradation enzymes of dopamine
MAO and COMT
Describe the receptors of dopamine
D1: stimulates cAMP and especially influences peripheral vessels
D2: decreases cAMP and influences vomiting centre in hypothalamus
D3: in limbic areas (emotion)
D2 and D4: affinity for certain antipsychotic drugs
Describe the intracellular (postsynaptic effects) (actions/functions) of dopamine
Low doses exogenous dopamine: bind to D1 receptors and cause splanchnic and renal vasodilation
Higher doses of exogenous dopamine: beta 1 effects (positively inotropic)
Very high doses of exogenous dopamine: alpha 1 effects - vasoconstriction with an increase in BP
Dopamine deficiency due to the degeneration of dopaminergic neurons, causes Parkinson’s disease (D2 receptors)
Schizophrenia: increased D2 receptor number / increase in their sensitivity
Dopamine inhibits prolactin secretion
Describe the distribution of serotonin
Hypothalamus, limbic system, cerebellum, SC, retina, GIT, and blood platelets
High [ ] in the brainstem
Describe the synthesis and clearance (disposal) of serotonin
Synthesis: tryptophan > 5-OH-tryptophan >serotonin (5-OH- tryptamine) > melatonin
* Serotonin inactivated by MAO catalyses to 5-OH indol-acetic acid (5HIAA)
Clearance: active uptake- serotonin increased in carcinoid syndrome ( a benign tumor of the small insteine that causes facial flushing, diarrhoea and cramps)
Describe the synthesis and clearance (disposal) of serotonin
Synthesis: tryptophan > 5-OH-tryptophan >serotonin (5-OH- tryptamine) > melatonin
* Serotonin inactivated by MAO catalyses to 5-OH indol-acetic acid (5HIAA)
Clearance: active uptake- serotonin increased in carcinoid syndrome ( a benign tumor of the small insteine that causes facial flushing, diarrhoea and cramps)
Describe the synthesis and clearance (disposal) of serotonin
Synthesis: tryptophan > 5-OH-tryptophan >serotonin (5-OH- tryptamine) > melatonin
* Serotonin inactivated by MAO catalyses to 5-OH indol-acetic acid (5HIAA)
Clearance: active uptake- serotonin increased in carcinoid syndrome ( a benign tumor of the small insteine that causes facial flushing, diarrhoea and cramps)
Describe the synthesis and clearance (disposal) of serotonin
Synthesis: tryptophan > 5-OH-tryptophan >serotonin (5-OH- tryptamine) > melatonin
* Serotonin inactivated by MAO catalyses to 5-OH indol-acetic acid (5HIAA)
Clearance: active uptake- serotonin increased in carcinoid syndrome ( a benign tumor of the small insteine that causes facial flushing, diarrhoea and cramps)
Describe the synthesis and clearance (disposal) of serotonin
Synthesis: tryptophan > 5-OH-tryptophan >serotonin (5-OH- tryptamine) > melatonin
* Serotonin inactivated by MAO catalyses to 5-OH indol-acetic acid (5HIAA)
Clearance: active uptake- serotonin increased in carcinoid syndrome ( a benign tumor of the small insteine that causes facial flushing, diarrhoea and cramps)
Describe the degradation enzymes of serotonin
MAO
Describe the receptors of serotonin
5HT1: Decrease in cAMP
5HT2: Increase in IP3 - also occur presynaptically (autoreceptors)
5HT3: Increase in cAMP - ligand-controlled Na+ ion channel; stimulation causes nausea and vomiting ( area postrema in hypothalamus)
