NEUROTRANSMITTERS AND THEIR RECEPTORS

Introduction

In this post we will be discussing about various different types of Neurotransmitters and their Receptors.

 Receptors

1.Ligand Gated- Ionotropic Receptor
2. Metabotropic- G-Protein Coupled Receptor

Some Important Terms 

1.Neurotransmitters(NT)- Excitation or Inhibition of post-synaptic terminal 
1a. Small Molecule NT - Glutamate, GABA, Glycine, Acetylcholine, Nor Epinephrine, Epinephrine, Dopamine, Serotonin.
1b. Large Molecule NT- Substance P, Enkephalin, Vasopressin

2.Neoromodulators- chemicals released released by neurons, modify the effect of neurotransmitters.
3.Auto Receptor- Presynaptic Receptor
4. IPSP-Inhibitory Post Synaptic Potential
5. EPSP - Excitatory Post Synaptic Potential
6. AMPA
7. NMDAR- N-Methyl D- Aspartate Receptor
8. IP3-Ionositol Triphosphate 
9. DAG-diacylglycerol

GABA

Major inhibitory neuron in the brain.

1.  GABA(A)                                          
  • CNS                                                  
  • ionotropic receptor                                        
  • causes increased Chloride in post synaptic membrane                           
  • causes IPSP                                                                                                       

2.  GABA(B)                                          
  • CNS                                                  
  • GPCR
  • causes increased IP3,DAG in post synaptic membrane                           
  • Increase K+, Decrease Ca++                                                                                                       

3.GABA(C)   
  • Retina                                                   
  • ionotropic receptor                                        
  • causes increased Chloride in post synaptic membrane                           
  • causes IPSP                                                                                                       

Agonists of GABA- Benzodiazepines, Barbiturates, Phenobarbital, enhance GABA(A) and inhibit AMPA

Glutamate

Main excitatory NT in brain and spinal cord.

Receptors-
1. Ionotropic- AMPA( increase Na+, Decrease K+)
                       NMDAR(increase Na+, Decrease K+, increase Ca++)     

2. Metabotropic- 

mGluR1-                              Increase IP3,DAG 
                                             Decrease K+, increase Ca++ 
mGluR5-                               Increase IP3,DAG 
                                              Decrease K+, increase Ca++ 
mGluR2, mGluR3-               decrease cAMP ,
                                              Increase K+, decrease Ca++ 
mGluR4,mGluR6, mGluR7-decrease cAMP ,
                                              decrease Ca++ 

#Glycine binding to NMDAR is essential for Glutamate binding.
#NMDAR blocked by Mg2+ , removed by AMPA 
# EPSP induced activation is slow for NMDAR
#In hippocampus NMDAR increase involved in memory
#Dysregulation of brain levels of mGluR5 has been linked to neurological disorders including schizophrenia, major depression disorder and autism.

Acetylcholine(Ach)

location- Neuromuscular Junction, in autonomic ganglia, postganglionic parasympathetic nerve target organ junctions and some post ganglionic sympathetic nerve target junctions.
Released by all neurons that exit CNS.

Receptors-
1. Nicotinic(Ionotropic) Receptors- increase Na+ in postsynaptic membrane
    Neuromuscular Junction(Nm) and CNS and autonomic ganglia(Nn)

2.Muscuranic Receptor
    M1,M4,M5- CNS
    M3-glands and smooth muscles
    M2- heart
    M1-also on autonomic ganglia

   M1,M3,M5-Increase IP3,DAG-- increase Ca2+
   M2,M4-decrease cAMP---increase K+ 


Nor Epinephrine(NE) and Epinephrine(E)

  • most sympathetic postganglionic endings(NE)
  • Epinephrine is methyl derivative of NE 
  • NE and E - Adrenal Medulla
  • E is not in sympathetic postganglionic endings
Receptors--
1.Alpha Adrenoreceptors (GPCR)
   Alpha1-heart , smooth muscles ---increase IP3, DAG--decrease K+
   Alpha2-CNS,pancreatic islets nerve terminals-- decrease cAMP-- decrease Ca++, increase K+

2.Beta Adrenoreceptors(GPCR--increase cAMP, decrease K+) 
   Beta 1- heart, JG cells 
   Beta 2-Bronchial , vascular smooth muscles
   Beta 3-adipose tissue 


Glycine

  • both excitatory and inhibitory
  • binds to NMDAR to make it more sensitive to Glutamate
  • Glycine mediates direct inhibition in the brainstem and spinal cord -- increase Chloride
  • Antagonist-- Strychnine
  • there 3 kinds of neurons in spinal cord that mediate inhibition-- release GABA, release Glycine , release both.

Dopamine

  • nigrostriatal pathway
  • mesocortical system- reward behavior and addiction in psychiatric disorders such as schizophrenia.
Receptors---
1. D1 like-- D1 and D5 (increase cAMP)
2. D2  like--D2, D3,D4(decrease cAMP)


Serotonin(5HT- 5 Hydroxy Tryptamine)

  • blood platelets, Gastro intestinal tract(enterochromaffin cells and myenteric plexus)
  • midline raphe nuclei-project to hypothalamus, limbic system, neocortex, cerebellum, spinal cord.
  • Receptors except 5-HT3 are GPCR
  • 5-HT3 present in GI tract and Area Postrema 
  • 5-HT4 present in GI tract - secretion and peristalsis.


N0(Nitric Oxide)

  • secreated by endothelium of blood vessels- Endothelium Derived Relaxing Factor(EDRF) Arginine------>NO
  • activates Guanylyl Cyclase 
  • not stored in vesicles
  • involved in synaptic plasticity

CO(Carbon monoxide)

  • diffusible gas
  • formed in CNS neurons and entire nervous system via degradation of heme by heme oxygenase.
  • can be intracellular messenger like NO.
  • role in olfaction, pain, long term potentiation.
  • endotoxin induced arginine vasopressin  release. 

Neuropeptide Y

  • Brain and ANS
  • GPCR---> inhibit adenyl cyclase, increase  Ca++
  • increases food intake, periphery vasoconstriction
  • acts on postganglionic sympathetic  nerve to reduce the release of NE 

Somatostatin

  •  Receptor in various parts of the brain.
  • Growth hormone inhibiting hormone(GHIH) in Hypothalamus, pancreas -inhibit insulin
  • All GPCR ---> inhibit adenyl cyclase

Substance P

  • Receptors -- Neurokinin Receptors NK1-NK3
  • all GPCR
  • Substance P is mediator at first synapse in pain transmission pathway in dorsal horn
  • in nigrostriatal pathway also

Opioid Peptides

  • Brain and GI tract contains receptors that bind morphine.
  • Enkephalins in nerve endings and GI tract and brain and function as synaptic transmitters.
  • found in substantia gelatinosa  .
  • Receptors - mu, kappa, delta (all are GPCR -- inhibit adenyl cyclase)

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