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)

Comments

Post a Comment

Popular posts from this blog

Blood Grouping in Humans, Uses, Disorders- Erythroblastosis fetalis

Image
What do we mean by blood grouping? The surface of RBC contains certain antigens. It is these antigens on the basis of which the blood groups are decided.   Different types of Blood Grouping ABO blood grouping- chromosome 9 (it has four different types of blood groups- A,B,AB,O) (AB blood group is a very good example of Co-dominance). Rh Antigen-If Rh antigen present then it is Rh +ve , and if absent then it is Rh -ve MN blood grouping-  chromosome 4 Duffy antigen- chromosome 1, first blood system antigen to be localized. Bombay blood group-Chromosome 19. Another antigen present on the RBC is the H antigen. H antigen is necessary for the expression of A,B antigens on the RBC surface. O blood group has got only the H antigen. Now if this antigen is also absent the surface RBC then it is known as the Bombay blood group.  Landsteiner's Law I - If an antigen is present on the RBC corresponding antibody must be absent in the plasma.      eg- A person with A blood...
Read more

Principles of Cardio-Pulmonary Resuscitation

Image
 How To Give CPR? INDICATIONS OF CPR 1.Cardiopulmonary Arrest: Cessation of breathing or beating of heart or both.   AIM OF CPR To provide oxygenated blood to all the organs of the body till the normal physiological function of the heart or lungs or both is regained. Plan For CPR The above plan should be performed in order Circulation, Airways, Breathing(mnemonic-CAB). Plan For CPR(for infants 0-1 year) All the procedure remains same, except the compressions should be made with two fingers of a hand. Compressions should be made at the site of the sternum 2-3 cm deep. Cardiopulmonary Resuscitation For Oneself If you feel any discomfort and sudden deep pain in the chest and inner border of the left hand(this is the most common site of pain in Myocardial infarction, other sites can be lower jaw, neck, lower back), strong voluntary coughing is advised. A breath and a strong forceful cough, alternately repeated after every 3s.   
Read more

Epilepsy

Image
    Postictal Period- Time after seizure for normal neurological function to resume. Aura- Precede Partial Seizures and include abnormal sensations.  What to do when someone undergoes a seizure? The following points should be taken into consideration- 1. STAY CALM & NEVER try to resist seizures of the patient. 2. Make the patient lie down and turn the person on one side. 3. Remove any sharp objects from the vicinity 4. Put a pen or something in between the teeth of the patient so that he/she doesn't bite his/her tongue. 5. Put a pillow/folded t-shirt/folded sweater below the head of the patient. 6. Remove patient's glasses if wearing one. 7.Do not give anything to eat or drink until he/she fully alert.. 8. Don't leave his/her side until the person regains consciousness.  9. Talk to the person and comfort him/her. 10. Remove anything tight around the neck so that the person can breathe freely. 11. Seek medical help.
Read more