Neurotransmitters

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1 SEMINAR ON NEUROTRANSMITTER RECEPTOR MECHANISM PRESENTED BY: AAFTAB ANWAR DEPARTMENT OF PHARMACOLOGY LUQMAN COLLEGE OF PHARMACY,GULBARGA

What are neurotransmitter? : 

What are neurotransmitter? Neurotransmitter are the chemical substance synthesized by nerve cell which transfer the information from pre synaptic to post synaptic neuron. 2

Neurotransmitters : 

3 Neurotransmitters Properties of neurotransmitters: 1) They should be synthesized in the presynaptic neuron 2) They should be Localized to vesicles in the presynaptic neuron 3) They should be Released from the presynaptic neuron under physiological conditions 4) They should be rapidly removed from the synaptic cleft by uptake or degradation 5) Presence of receptor on the post-synaptic neuron. 6) They should be Binding to the receptor elicits a biological response

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6 Neurotransmitters found in the nervous system EXCITATORY Acetylcholine Aspartate Dopamine Histamine Norepinephrine Epinephrine Glutamate Serotonin INHIBITORY GABA Glycine

Acetylcholine synthesis: : 

7 Acetylcholine synthesis: In the cholinergic neurons acetylcholine is synthesized from choline. This reaction is activated by cholineacetyltransferase As soon as acetylcholine is synthesized, it is stored within synaptic vesicles.

Release of acetylcholine from presynaptic neurons: : 

8 Release of acetylcholine from presynaptic neurons: 1)When the nerve impulse (Action potential) moves down the presynaptic axon to the terminal bulb the change in the membrane action potential causes the opening of voltage gated calcium channels open allowing Ca+2 ions to pass from the synaptic cleft into the axon bulb. 2)  Within the bulb the increase in Ca+2 concentration causes the synaptic vesicles that contain acetylcholine to fuse with the axonal membrane and open spilling their contents into the synaptic cleft.

Binding of acetylcholine to the postsynaptic receptors: : 

9 Binding of acetylcholine to the postsynaptic receptors: The postsynaptic membrane of the receptor dendrite has specific cholinergic receptors toward which the neurotransmitter diffuses. Binding of acetylcholine trigger the opening of ion channels in the postsynaptic membrane initiating action potential that can pass in the next axon. Acetylcholine receptors: Acetylcholine receptors are ion channels receptors made of many subunits arranged in the form [(α2)(β)(γ)(δ)]. When Acetylcholine is not bounded to the receptors, the bulky hydrophobic leu side close the central channels preventing the diffusion of any ions. Binding of two acetylcholine molecules to the receptors will rotate the subunits in which the smaller polar residues will line the ion channel causing the influx of Na+ into the cell and efflux of K+ resulting in a depolarization of the postsynaptic neuron and the initiation of new action potential.

Removal of Acetylcholine from the synaptic cleft: : 

10 Removal of Acetylcholine from the synaptic cleft: In order to ready the synapse for another impulses: 1)      The neurotransmitters, which are released from the synaptic vesicles, are hydrolyzed by enzyme present in the synaptic cleft “Acetylcholinestrase” giving choline, which poorly binds to acetylcholine receptors.   Acetylcholine + H2O Choline + H+ acetate 2)      The empty synaptic vesicles, which are returned to the axonal terminal bulb by endocytosis, must be filled with acetylecholine.

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11 Other Neurotransmitters:

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Summary:

Receptor : 

Receptor It is defined as the sensing elements in system of chemical communication that co-ordinates the function of all different cell in the body. It situated inside or at surface of effecter cell , agonist combine them to initiate response. 13

Receptors are macromolecular component of cell which regulate the critical function like-enzyme activity,permeability,transport processes. : 

Receptors are macromolecular component of cell which regulate the critical function like-enzyme activity,permeability,transport processes. 14

Receptor mechanism : 

Receptor mechanism Administration of drug produce it effect on physiological system of body. Most of the drug act by associating with specific macromolecule that alters biochemical/biophysical activities. The broad concept behind this is “RECEPTOR”. 15

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16 LIGAND : Attaches selectively to particular receptor or sites that indicates only affinity without regard to functional change. When agonist bind with receptor several process takes place- Receptor activation in to functional response called transducer mechanism. Depending upon transducer mechanism and pharmacology they have , receptor are divided, 1)Ion channel linked receptor 2)G-protein coupled receptor 3)Enzyme linked receptor

Ion channel linked receptor : 

Ion channel linked receptor Also known as inotropic receptor. These are surface membrane protein with a similar structure to that of ion channel but incorporating a ligand binding site. These are receptor with fast transmitter acting at synapse in milliseconds. EX-nicotinic Ach receptor,GABAA receptors. 17

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18 These are transmit signal across plasma membrane by transmembrane conductance of ion. They enclosed ion selective channel (Na,k,ca, or cl) within their molecule.

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19 GATING: Voltage gated channels It is sub divided by following-

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2. ligand-gated calcium channels 3.Calcium release channels 4.Store operated calcium channels 20

G- Protein Coupled Receptor : 

G- Protein Coupled Receptor They called G-proteins because of their interaction with guanine nucleotide GTP and GDP. It consist of 3 subunits alpha, beta and gamma Molecular Structure:- GPCRs consist of single polypeptide chain up to 1100 residues. They have characteristic 7 transmembrance alpha helices similar to ion channels. 21

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22 Classification

REFRENCES : 

REFRENCES THE PHARMACOLOGICAL BASIS OF THERAPEUTICS BY : GOODMAN & GILMAN’S PHARMACOLOGY BY : H.P.RANG & M.M.DALE WWW.GOOGLE.COM 23

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24 THANK YOU