生理學(xué)教學(xué)課件：24-nervous system-2

1、 Neurotransmitter & Receptor PUMC & CAMS Xue Gao Ways of Neurons Communication u Definition: Endogenous signaling molecules that are synthesized & liberated by presynaptic neuron into the synaptic cleft, then combine with receptor in postsynaptic neuron or effector cell, cause a specific biological

2、effect u Neuromodulator: Synthesized & liberated by presynaptic neuron to modulate the effect of neurotransmission Neurotransmitter Characters that a classical neurotransmitter must be n Synthesized by presynaptic neurons n Released into synaptic cleft n Combine with receptors located at postsynapti

3、c neuron n Removed in a specific way n Have specific Agonist & Antagonist Some substances e.g. CO & NO act as neurotransmitter Classification of neurotransmitter u Small-molecule, rapidly acting transmitters p Class I: Acetylcholine p Class II: Amines Norepinephrine, Epinephrine, Dopamine, Serotonin

4、, Histamine p Class III: Amino Acids GABA, Glycine, Glutamate, Aspartate p Class VI: NO, CO u Large-molecule, slowly acting transmitters p Neuropeptide u Small-molecule transmitter: p In most cases, they are synthesized in the cytosol of presynaptic terminal p Most often the effect is to increase or

5、 decrease conductance through ion channels p The transmitter are continually recycled & used over and over again u Large-molecule transmitter: They are synthesized as integral part of large protein molecules by ribosomes in the neuronal cell body The transmitter vesicles are transported all the way

6、to the tip of nerve fiber by axonal streaming of the axonal cytoplasm at a very slow rate The vesicles is autolyzed & is not reused Synaptic Vesicles p One neuron axon terminal may contain two or more kinds of neurotransmitter in different synaptic vesicles that can be distinguished using the electr

7、on microscope Neurotransmitter Co-existence PK (Dale Principle) Neurotransmitter Co-existence Neurotransmitter co-existence n Definition: Proteins on the cell membrane or in the cytoplasm that could bind with specific neurotransmitters & alter the behavior of postsynaptic neurons or effector cell Re

8、ceptor uAgonist: A substance that mimics a specific neurotransmitter, is able to attach to that neurotransmitters receptor & thereby produces the same action that the neurotransmitter usually produces uAntagonist (Blocker): A substance that bind to but do not activate receptors, thereby blocking the

9、 actions of neurotransmitter Ligand of receptor u Receptor quantity & affinity can be changed in different condition p Up-regulation p Down-regulation Regulation of Receptor Western blot p According to the “l(fā)igand” p According to the “l(fā)ocation”: Membrane (transmembrane) receptor Cytoplasmic receptor

10、 Nuclear receptor Receptor Classification p According to -“Mechanism of Receptor Activation” Receptor Classification u Ion Channel-linked Receptor u G Protein-Coupled Receptor u Enzyme-linked Receptor (6 known types) Presynaptic Receptor (Autoreceptor) Ion Channel-linked Receptor Receptor directly c

11、ontrols channel Fast reaction G Protein-Coupled Receptor u Receptor indirectly controls channel (Second Messenger System) u 1st Messenger: Neurotransmitter u 2nd Messenger: p cAMP/cGMP p IP3 p DAG p Ca2+ u Slow & Prolonged Reaction G Protein-Coupled Receptor Some Important Transmitters u Acetylcholi

12、n u Catecholamines p Dopamine p Norepinerphrine p Epinephrine u Amino Acids p Glutamate (+) p GABA ( -amino butyric acid) (-) Acetylcholine (Ach) Ach Synthesis Choline+ Acetyl CoAAch + CoA Choline Acetyltransferase Ach - Distribution u Peripheral Nervous System (PNS): p Neuro-Muscular junction: Moto

13、r neuron innervated the skeletal muscles p Preganglionic neurons of autonomic NS p Postganglionic neurons of parasympathetic NS p Few postganglionic neurons of sympathetic NS u Central Nervous System (CNS) - Widespread u Muscarinic Receptors: M Receptor -Subtype: M1M5 u Nicotinic Receptors: N Recept

14、or -Subtype: N1 & N2 Ach Receptors (Cholinergic Receptor) n - Subtype: M1M5 - G Protein-Coupled Receptor - Parasympathetic target organs - Some sympathetic target organs (Sweat glands, Sympathetic vasodilator nerve) - Antagonist: Atropine Muscarinic Receptors: M Receptor Muscarine-like action u Inhi

15、bition of cardiac activity u Constriction of bronchial smooth muscle, gastrointestinal smooth muscle, bladder detrusor muscle u Increasing of digestive gland & sweat gland secretion u Dilation skeletal muscle vessel Ach -Heart Effect Muscarine-like action n -Subtype: N1, Neuronal type N2, Muscle typ

16、e - Ion Channel-linked Receptor - Distribution: N1:Autonomic postganglia N2: Neuromuscular junction (Motor Endplate membrane） - Antagonist: Tubocurarine Nicotinic Receptors: N Receptor Na+ inflow k+ outflow Nicotin-like Action The Life Cycle of Ach Henry Hallett Dale Otto Loewi for their discoveries

17、 of Ach as neurotransmitter” 1936 Nobel Prize in Medicine u Dopamine u Norepinerphrine u Epinephrine Catecholamines Synthesis CNS CNS & PNS CNS Dopamine (DA) u Receptor: D1D5 u All are G Protein-Coupled Receptor u Mainly involved in Somatic movement， emotion，cardiovascular activity，et al Epinephrine

18、 u Mainly involved in cardiovascular activity Norepinephrine (NE) n Found both in PNS & CNS n PNS: -Postganglionic neurons of sympathetic nerve nCNS: -Regulation of General Behavior, e.g. Cardiovascular Activity, Body Temperature All receptors are G Protein-Coupled Receptor Constriction of Vessel &

19、uterus Relaxation of small intestine Relaxation of Vessel & uterus, small intestine, bronchial Exciting Cardiac activity Excitatory Amino Acid u Glutamate / Glutamic Acid (Glu) Glutamate Synthesis Amino Acid Neurotransmitter Glutamate Receptor Ion Channel-linked Receptor G-protein Linked Receptor EA

20、ATs： Excitatory Amino Acid Transporters VGLUTs： Vesicular Glutamate Transporters xCT： Glutamate- Cystine exchanger Glutamate Transporters NMDA Receptor Ca2+/Na+ u Mg+ is voltage-dependant blocker u Quantity & location at the postsynaptic membrane is relative stable u Induce Slow & Prolonged postsyna

21、ptic membrane depolarization reaction u Ca2+ is the main inflow ion Characters of NMDA Receptor Na+/Ca2+ n Na+ is the mail inflow ion n Induce Fast Postsynaptic Membrane Depolarization Reaction n Have the property of desensitization quickly n Quantity & location at the postsynaptic membrane is unfix

22、ed Characters of AMPA Receptor Wandering Receptor AMPA receptor q AMPA receptors can move between an intracellular pool and the neuronal surface by the processes of exocytosis and endocytosis q AMPA receptors can also move by lateral diffusion in the plasma membrane until they are captured and immob

23、ilized by putative anchoring proteins concentrated in postsynaptic regions q AMPA receptors are also immobilized by increases in intracellular calcium levels Way of AMPA-R Wondering Chinese Restaurant Syndrome MSG: Monosodium Glutamate Reaction Process of Ionotropic Glutamate Receptor Synaptic Plast

24、icity u Definition: Repeated activity of synapse may induce the long term change of synaptic morphology & function or synaptic transmission efficiency l iGluRs may be involved in long term synaptic plasticity, including: p Long term potential (LTP) p Long term depression (LTD) u Definition: is a lon

25、g-lasting enhancement in “amplitude of postsynaptic potential” (synaptic strength) u LTP is widely considered one of the major cellular mechanisms that underlies “l(fā)earning & memory” Long Term Potential (LTP) -(NMDAR/AMPAR & LTP) LTP mechanism n Definition: is a long lasting reduction in synaptic strength n LTD is thought to result mainly