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Neurotransmitters M.Prasad Naidu MSc Medical Biochemistry, Ph.D.Research Scholar
Neurotransmitters is a chemical substance or chemical messenger (within brain) that is secreted by neurons and that allow communication between nerve cells to produce physiological response such as muscle contraction. • Neurotransmitters are chemical substances secreted by neurons and they convey messages from one neuron to a target cell. • At the target cells, the neurotransmitters may alter ion flow (depolarise or hyperpolarise), or they may alter the cellular metabolism. • The transmitter substances carry out the actual passage of a signal across a synapse.
Neurotransmitters are the principal signal molecules that mediate their actions via receptors that can function as ion channels. The neuron • The neuron is the structural and functional unit of the nervous system. • Neurons function by the production, propagation and transfer of nerve impulses. • The functional components of a neuron consists of - the cell body (perikaryon) having the nucleus (karyon) and those organelles that maintain the cell. - the processes extending from the cell body which consists of axon and dendrites.
Synapses • A Synapse is a site of functional contact between neurons that facilitate transmission of impulses from one (presynaptic) neuron to another (postsynaptic) neuron or effector (target) cells such as muscle and gland cells. • Synapse is a site of neuron-to-neuron or neuron-to-effector cell communication. • A typical Synapse contains presynaptic bouton or knob, synaptic cleft and postsynaptic membrane.
Classification of neurotransmitters • Class Amine – • Examples are epinephrine, norepinephrine, dopamine and serotonin (5-hydroxytryptamine). • Class Amino acid and amino acid derivatives – • Examples are glutamate, aspartate, glycine, histamine and GABA. • Class Purines – • Examples are adenosine, ATP. • Class Gas – • Examples are nitric oxide • Class Miscellaneous
Examples are acetylcholine • Acetyl choline • Acetylcholine • The first chemical neurotransmitter identified was acetylcholine. • Synthesis and storage • Release and action • Reuptake and degradation • Acetylcholine receptors – muscarinic and nicotinic acetylcholine receptors. • Cholinergic agonists are nicotine, muscarine and α-latrotoxin.
Cholinergic antagonists are atropine (and related compound scopolamine), botulinus toxin, α-bungarotoxin and d-tubocurarine (muscle relaxant).
Catecholamines • The principal catecholamines are norepinephrine (noradrenaline), epinephrine (adrenaline) and dopamine. • Synthesis • Storage • Release • Receptors and action • Reuptake and degradation • Functions of catecholamines
Serotonin • Serotonin also called 5-hydroxytryptamine (5-HT). • Storage and release • Reuptake and degradation • Functions
GABA (Gamma Aminobutyric Acid) • Synthesis • Receptors and action • Reuptake and degradation • Functions of GABA
Histamine • Synthesis and receptors • Functions • Degradation
Glycine • Glycine is the inhibitory neurotransmitter in the spinal cord. • Receptors and action • Reuptake and degradation • Functions of glycine
Glutamate • Glutamate is the excitatory amino acid neurotransmitter in the brain. • Receptors and action • Reuptake and degradation • Functions
Nitric oxide (NO) • Nitric oxide also has been identified as a neurotransmitter. • Synthesis • Degradation • Functions
Clinical importance • Acetylcholine agonists with acetylcholinesterase inhibitors have significant medical application in the treatment of disorders such as - glaucoma by increasing the tone of the muscles of accomodation of the eye. -myasthenia gravis -in terminating the effects of neuromuscular blocking agents such as atropine.
Myasthenia gravis – auto antibodies form to nicotinic type acetylcholine receptors which destroy some receptors and compete with acetylcholine to bind to the surviving receptors. • Treatment may include administration of acetylcholine esterase inhibitors (e.g., pyridostigmine, neostigmine) to prolong activity of acetylcholine at motor end plates. • Alzheimer’s disease – tacrine used in treatment of alzheimer’s disease is a long-acting cholinesterase inhibitor.
Catecholamines • β – blockers, such as atenolol, are used to treat hypertension and chest pain (angina) in ischaemic heart disease because they antagonise the stimulatory effects of catecholamines on the heart. • β2 – receptor agonists such as salbutamol which stimulates β – receptor of lungs, are used to produce bronchial dilation in asthma without stimulating β1 – receptor in the heart. • D2 – receptors (of dopamine) antagonist such as phenothiazines and haloperidol are used as a antipsychotic drugs.
Parkinson’s disease • Treatment may involve administration of • Drugs such as deprenyl that inhibit the degradation of dopamine and other biogenic amines by monoamine oxidase type B • L-dopa that can cross the blood-brain barrier and serve as a substrate for dopamine biosynthesis in striatal cells.
GABA • The anxiolytic drugs like diazepam and barbiturate, sleep inducing and an anticonvulsant drug used in the treatment of epilepsy, exert their soothing effects by potentiating the binding of GABA to GABA-A receptors.
Serotonin • Depression • Treatment may include administration of tricyclic anti-depressants that inhibit uptake of both noradrenaline and adrenaline into brain cells, or other antidepressants such as fluoxetine (prozac) that preferentially inhibit serotonin uptake inhibitors of monoamine oxidase A that convert serotonin to an inactive aldehyde may also be used.
Histamine • H1 – receptors antagonists such as diphenhydramine are used in the treatment of allergic responses and for asymptomatic treatment of upper respiratory disorders. • H2 – receptors antahonists such as ranitidine or cimtidine are used in the treatment of peptic ulcers. • H2 – receptor inhibitors have no effect on allergy.