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SITI NUR BAIZURY BT HASSAN 10-3-96 Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target

cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane in the axon terminal, on the presynaptic side of a synapse. They are released into and diffuse across the synaptic cleft, where they bind to specific receptors in the membrane on the postsynaptic side of the synapse.They can be divided according to their chemical structure which are amino acid, monoamines and peptides.

Differences between neurotransmitter and neurohormones

NEUROTRANSMITTER Endogenous chemicals that transmit signals from a neuron to a target cell across a synapse packaged into synaptic vesicles clustered beneath the membrane in the axon terminal, on the presynaptic side of a synapse. Examples: acetylcholine, GABA or dopamine.

NEUROHORMONE Any hormone produced and released by neuroendocrine cells into the blood.

secreted into the circulation for systemic effect and also have a role of neurotransmitter or other roles as autocrine (self) or paracrine (local) messenger.

Examples: TRH (Thyrotropin releasing hormone), dopamine or epinephrine.

neurohormones

neurotransmitter

Mechanism of action

1. The action potential in the presynaptic cell is transmitted to the postsynaptic cell via a chemical signal, which, in turn, triggers an action potential in the postsynaptic cell. 2. When the action potential of the presynaptic cell reaches the terminal bulb, it triggers the opening of voltage-gated calcium channels in the plasma membrane. 3. Calcium ions flow into the presynaptic cell. 4. The elevated intracellular concentration of calcium triggers the fusion of synaptic vesicles with the plasma membrane of the terminal bulb. The synaptic vesicles reside in the terminal bulb, filled with neurotransmitters. 5. When they fuse with the plasma membrane, the neurotransmitters are released into the synaptic cleft. 6. Extracellular neurotransmitters bind to specific receptors in the plasma membrane of the postsynaptic cell. 7. Upon the binding of neurotransmitter to its receptor, an action potential is triggered in the postsynaptic cell .Release of neurotransmitters usually follows arrival of an action potential at the synapse, but may also follow graded electrical potentials. Low level "baseline" release also occurs without electrical stimulation. Some neurotransmitters are commonly described as "excitatory" or "inhibitory". The only direct effect of a neurotransmitter is to activate one or more types of receptors. The effect on the postsynaptic cell depends, therefore, entirely on the properties of those receptors

Few examples of important neurotransmitter actions: Glutamate:

fast excitatory synapses in the brain and spinal cord. It is also used at most synapses that are "modifiable", i.e. capable of increasing or decreasing in strength. Excess glutamate can overstimulate the brain and causes seizures. Modifiable synapses are thought to be the main memory-storage elements in the brain. Excessive glutamate release can lead to excitotoxicity causing cell death.

GABA:

fast inhibitory synapses in virtually every part of the brain. Many sedative/tranquilizing drugs act by enhancing the effects of GABA. Correspondingly glycine is the inhibitory transmitter in the spinal cord. Acetylcholine:

transmitter at the neuromuscular junction connecting motor nerves to muscles. The paralytic arrow-poison curare acts by blocking transmission at these synapses. Acetylcholine also operates in many regions of the brain, but using different types of receptors, including nicotinic and muscarinic receptors.

Dopamine:

more than one functions in the brain; this includes regulation of motor behavior, pleasures related to motivation and also emotional arousal. It plays a critical role in the reward system; people with Parkinson's disease have been linked to low levels of dopamine and people with schizophrenia have been linked to high levels of dopamine. Serotonin

is a monoamine neurotransmitter. Most is produced by and found in the intestine (approximately 90%), and the remainder in central nervous system neurons. It functions to regulate appetite, sleep, memory and learning, temperature, mood, behaviour, muscle contraction, and function of the cardiovascular system and endocrine system. It is speculated to have a role in depression, as some depressed patients are seen to have lower concentrations of metabolites of serotonin in their cerebrospinal fluid and brain tissue.

Substance P

undecapeptide responsible for transmission of pain from certain sensory neurons to the central nervous system. It also aids in controlling relaxation of the vasculature and lowering blood pressure through the release of nitric oxide. There are two types of Neurotransmitter receptors: ligand-gated receptors or ionotropic receptors and G protein-coupled receptors or metabotropic receptors

IONOTROPIC transmembrane molecules that can open or close a channel that would allow smaller particles to travel in and out of the cell Not opened (or closed) all the time. They are generally closed until another neurotransmitter binds to the receptor.

METABOTROPIC do not have a channel that opens or closes but are linked to another small chemical called a Gprotein.

Ligand binds,receptor activates GProtein.Once activated, the G-protein itself goes on and activates another molecule secondary messenger. Take a longer times depending on the number of steps (secondary messengers), required to produce a response

Act very quickly. As soon as a ligand binds to them, they change shape and allow ions to flow in. Ligand doesnt stay in place very long and channel closes back very quickly.

Wider range of responses.

Functional Classification of Neurotransmitters Neurotransmitter effects may be excitatory (depolarizing) and/or inhibitory (hyperpolarizing) Determined by the receptor type of the postsynaptic neuron GABA and glycine are usually inhibitory Glutamate is usually excitatory Acetylcholine-Excitatory at neuromuscular junctions in skeletal muscle Gaseous neurotransmitter Nitric oxide Nitric oxide (NO) plays important roles in the brain in general and in neuroendocrine functions in particular.

Nitric oxide serves as a neurotransmitter between nerve cells, part of its general role in redox signaling. Unlike most other neurotransmitters that only transmit information from a presynaptic to a postsynaptic neuron, the small, uncharged, and fat-soluble nitric oxide molecule can diffuse widely and readily enters cells. Thus, it can act on several nearby neurons, even on those not connected by a synapse. At the same time, the short half-life of NO means that such action will be restricted to a limited area, without the necessity for enzymatic breakdown or cellular reuptake. NO is also highly reactive with other free radicals, lipids, and proteins. NO-cGMP cascade is involved in learning and memory through the maintenance of longterm potentiation (LTP). Nitric oxide is an important non-adrenergic, non-cholinergic (NANC) neurotransmitter in various parts of the gastrointestinal tract. It causes relaxation of the gastrointestinal smooth muscle. In the stomach it increases the capacity of the fundus to store food and fluids. Carbon Monoxide Carbon monoxide used to cement memories in the hippocampus of the brain and that established memories might be erased when carbon monoxide is absent. Carbon monoxide might protect against excess neuronal activity, dampening nerves that are firing too much. In this way, it could counter some of the adverse effects of nitric oxide, Dr. Snyder said. For example, nitric oxide seems to cause damage in strokes, when nerve cells are stimulated to fire repeatedly. Carbon monoxide, he said, could counter that effect. In large concentrations, carbon monoxide is a poison. It binds so tightly to the heme chemical group at the heart of hemoglobin molecules that it prevents oxygen from binding. In the presence of carbon monoxide, red blood cells are unable to carry oxygen to body tissues. But it was this very ability of carbon monoxide to bind to heme that gave the researchers a clue to the gas's normal role in transmitting nerve signals. http://www.nytimes.com/1993/01/26/science/carbon-monoxide-gas-is-used-by-brain-cells-asa-neurotransmitter.html
http://web.williams.edu/imput/synapse/pages/III.html http://en.wikipedia.org/wiki/Neurohormone

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