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Related Experiment Videos

Spare cholinergic receptors in the urinary bladder

G F Anderson, B H Marks

    The Journal of Pharmacology and Experimental Therapeutics
    |June 1, 1982
    PubMed
    Summary

    Carbachol elicits mechanical responses in rabbit detrusor muscle at much lower concentrations than those required for calcium uptake or receptor binding. This suggests a significant muscarinic receptor reserve in the bladder.

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    Area of Science:

    • Pharmacology
    • Physiology
    • Urology

    Background:

    • Detrusor muscle contraction is mediated by muscarinic receptors.
    • Understanding the concentration-response relationship of agonists is crucial for bladder function studies.

    Purpose of the Study:

    • To investigate the concentration-effect relationships of carbachol on rabbit detrusor muscle.
    • To compare carbachol's effects on mechanical response, calcium uptake, and muscarinic receptor binding.

    Main Methods:

    • Studied carbachol's concentration-effect curves for mechanical response and 45Ca uptake.
    • Utilized lanthanum-residual wash out method for calcium uptake.
    • Performed [3H]quinuclidinyl benzilate (QNB) binding assays with Scatchard analysis on muscle homogenates.

    Main Results:

    • EC50 for mechanical response was 0.27 microM; for 45Ca uptake, it was 12.7 microM.
    • [3H]QNB binding revealed a KD of 0.074 nM and receptor density of 47.2 fmol/mg protein.
    • Carbachol displacement of [3H]QNB had an EC50 of 135 microM and a Ki of 42 microM.

    Conclusions:

    • Mechanical response requires significantly lower carbachol concentrations than 45Ca uptake or receptor occupancy.
    • A substantial muscarinic receptor reserve (approximately 150-fold) exists in the rabbit detrusor muscle.

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