Muscarinic Receptors:Organ Bath

Cholinergic muscarinic receptors
1. Prejunctionally
2. Postjunctionally
ACH muscurinic Receptors
1. Plasma membrane receptors
2. Mediate signal transduction coupling
  1. Heterotrimeric guanine nuecleotide binding protiens (G-proteins)
Five Subtypes
1. M4
2. M3
  1. Mediates all contactile responses in vitro.
  2. Act via a variety of secondary messagers
    1. Cause direct smooth muscle contraction
  3. Activates phospolipase C (PLC)
    1. Via Gq protiens
3. M2
  1. 75% Population share.
    1. Pig detrusor muscle
4. M5
5. M1
Similar 3 dimentional structures
1. Single protein seven transmembrane domains
  1. Linked by 3 intracellular and three extra cellular loops
Antagonist
1. Drug that block/partilly block a response
  1. Competative anatagonist binds reversibily to the same receptor as the agonist
2. Dose Response Curve
  1. Fixed concentration of antagonist will be shifted to the right
3. Not completly selective
  1. Tool for discriminating muscarinic receptor subtypes in a given tissue
4. Obtaining affinity constant (pK) or affinity estimates (pA2)
  1. For Currently available antagonist to generate an affinity profile of these drugs at functional muscarinic receptors
    1. To find pK2 and pA2 for specific receptor antagonist, concentration-response curve
      1. to a muscarinic receptor agonist in absence and presence of specific receptor
        Postjunctional contractile responses of muscle tissue at each concentration are measured to find plateau
        between agaonist and magnitude of the effect produced is : concentration-response/dose response relationship.
      2. pKb = log (CR1)- LOG [B]
        CR= Concentration ratio
        extent of shitf in the concentration -response curve in presence of an antagonist.

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Muscarinic Receptors:Organ Bath

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	Created by David Bone about 10 years ago