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ISORECEPTORS & CRYPTIC RECEPTOS

Dr. Tamseela Mumtaz

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Iso receptors

  • Isoreceptors are structurally and functionally distinct receptors for the same hormone
  • Such receptors have different tissue distributions, second messengers and functions
  • All the receptors in a single class recognize same natural hormone, other ligands must be used to distinguish among them

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example

  • Nicotine preferentially binds to acetylcholine receptors on skeletal muscle, whereas muscarine is more specific to those receptors in the parasympathetic nervous system
  • These receptors are named based on their agonist
  • Iso receptors are very common but some hormones have only one receptor such as insulin except for slight variation in glucosylation

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Why would one hormone have multiple receptors ?��

  • Isoreceptors allow hormone to have widely diverse, even opposite, effects in different tissues.
  • Adrenergic receptors provide an excellent example

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  • Catecholamins, like other hormones have numerous actions that are related to single overall function
    • Flight or fight response
    • Smooth muscle contract
      • bladder sphincter to prevent voiding
      • Mesenteric arterioles to shift blood to the skeletal muscle

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    • Smooth muscle relax
      • In the air way to increase oxygenation
      • In the intestine to deffered digestion
    • Effect on metabolism
    • Cardiovascular activity

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    • THESE DIVERSE ACTIONS WOULD BE DIFFICULT TO ELICIT WITH A SINGLE RECEPTOR AND A SECOND MESSENGER

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The Catecholamines: Mechanism of Signaling�

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  • Binding to β1 and β2 ;
    • Stimulates G-proteins coupled to adenylate cyclase.
  • Binding to α2 ;
  • - Inhibits adenylate cyclase.
  • Binding to α1
    • Is coupled to phospholipase C,
    • Increases Phosphoinsitol, DAG and Ca2+

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Pharmacological importance of isoreceptors

  • Isoreceptors can also extend dose response of a system
    • Fat cell contain β1, β2 and β3 adrenergic receptors, all of which mediate lipolysis
    • Their hormone responsiveness is different
      • β1AR is most sensitive
      • β3AR is least sensitive
    • These isoreceptors allow the fat cell to respond to a wide range of catecholamine concentrations

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Cryptic Receptors

  • Number of receptors increase suddenly without an obvious explanation……

WHY????

HOW?????

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Cryptic Receptors

  • Receptors already exist in some latent form incapable of hormone binding…… that’s why called cryptic receptors

Inducing factors is

  • Stimulating the conversion of latent receptors to overt one

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Mechanism

  • Several possible mechanism
      • Receptor undergo conformational changes by
        • Phosphorylation
        • Sulfhydryl modification
        • Cleavage

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Examples

    • The GnHR receptors can be unmasked by
      • Phosphorylation
      • deglycosylation

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  • The neuropeptide Y1 receptor can be exposed by sulfhydral modification
  • Insulin receptors can be debunk by cleavage

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Phosphorylation of GnRH

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Cleavage of insulin

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  • Perturbation of the environment of receptors can also increase the total number of binding sites in the absence of protein synthesis
  • Detergents, phospholipases, phospholipid methylation and cholesterol sequestering reagents can induce the phenomenon.

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  • Energy depletion can lead to appearance of additional receptors
  • These membrane proteins may represent a ready reservoir of receptors for rapid cellular response

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References

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