Spare receptor

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SPARE RECEPTOR/ RECEPTOR RESERVE C VELMURUGAN, M.PHARM ( Ph.D ), Department of pharmacology, Sri krishna Chaithanya College of Pharmacy, Madanapalle , Chittoor-517325.

Spare receptor/Receptor reserve :

Spare receptor/Receptor reserve Receptors are said to be "spare" for a given pharmacologic response when the maximal response can be elicited by an agonist at a concentration that does not result in occupancy of the full complement of available receptors. Or Max response elicited by [agonist] that doesn’t occupy all avail receptors Spare receptors are not qualitatively different from non spare receptors. They are not hidden or unavailable, and when they are occupied they can be coupled to response. Each cell have a receptor reserve. Receptor reserve is dependent on the tissue and the used drug. A high spare receptor concentration makes the system more sensitive for low ligand concentrations Partial agonists can become full agonist if a receptor reserve exists

Spare receptor/Receptor reserve :

Spare receptor/Receptor reserve A responding cell with four receptors and four effectors. Here the number of effectors does not limit the maximal response, and the receptors are not spare in number. Consequently, an agonist will occupy 50% of the receptors, and half of the effectors will be activated, producing a half-maximal response (ie, two receptors stimulate two effectors). Now imagine that the number of receptors increases 10-fold to 40 receptors but that the total number of effectors remains constant. Most of the receptors are now spare in number. As a result, a much lower concentration of agonist suffices to occupy two of the 40 receptors (5% of the receptors), and this same low concentration of agonist is able to elicit a half-maximal response.

Spare receptor-Dose effect curve :

Spare receptor-Dose effect curve 100 0 0 Effect Ligand concentration (log scale) spare fraction no spare receptors spare receptors

Spare receptor-Receptor occupancy curve .:

Spare receptor-Receptor occupancy curve . Effect (%) Receptor saturation (%) spare fraction no spare receptors spare receptors 100 100 0 0

DRUGS BEHAVIOR IN THE PRESENCE OF SPARE RECEPTORS:

DRUGS BEHAVIOR IN THE PRESENCE OF SPARE RECEPTORS Agonists apparent higher potency Competitive antagonists apparent lower potency irreversible antagonists apparently competitive, until higher concentrations are reached Partial agonists higher efficacy > full agonists

Spare receptors - full agonist :

Spare receptors - full agonist Adrenergic receptor in myocardium 10% of receptor occupied by adrenaline produce more response (force of contraction)

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Results in different tissue sensitivities to same agonist Different tissues have different spare receptors for same agonist agonist full efficacy in one tissue, partial efficacy in another PHYSIOLOGY OF SPARE RECEPTORS

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Logarithmic concent-response curves for a single agonist acting on the same receptor subtype in tissues with different proportions of spare receptors (A, B, C, and D)  muscle contraction in vitro. Note all tissues show same max response to drug (intrinsic activity). The agonist shows highest potency (lowest EC50) at tissue with greatest proportion of spare receptors (A), and lowest potency at tissue with lowest proportion of spare receptors (D).

Spare receptors - full agonist Vs competitive antagonist :

Spare receptors - full agonist Vs competitive antagonist Acetylcholine and atropine on muscuranic receptor Acetylcholine receptor in skeletal muscle (Nm) botulinium toxin from clostridium will not affect the Ach response [musle twitch(spasmodic muscle contraction)] in skeletal muscle upto 50% of receptor occupied.

Spare receptors – agonist Vs irreversible antagonist:

Spare receptors – agonist Vs irreversible antagonist Some receptor antagonists bind to the receptor in an irreversible . The antagonist's affinity for the receptor may be so high, the receptor is unavailable for binding of agonist. The antagonists in this class produce irreversible effects because after binding to the receptor they form covalent bonds with it. After occupancy of some proportion of receptors by such an antagonist, the number of remaining unoccupied receptors may be too low for the agonist (even at high concentrations) to elicit a maximal response. If spare receptors are present, however, a lower dose of an irreversible antagonist may leave enough receptors unoccupied to allow achievement of maximum response to agonist, although a higher agonist concentration will be required

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Spare receptors - Partial agonist F u l l r e s p o n c e S p a r e r e c e p t o r s F u l l a g o n i s t W e a k r e s p o n c e P a r t i a l a g o n i s t F u l l r e s p o n c e

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