EFFECTS OF ACUTE AND CHRONIC BOTULINUM TOXIN TREATMENT ON RECEPTOR NUMBER, RECEPTOR DISTRIBUTION AND TISSUE SENSITIVITY IN RAT DIAPHRAGM

  • 1 January 1977
    • journal article
    • research article
    • Vol. 200  (2) , 343-351
Abstract
Tritiated .alpha.-bungarotoxin was used to determine the number and distribution of acetylcholine receptors in innervated, denervated and botulinum toxin-treated muscles. Innervated hemidiaphragms bound approximately 2.3 .times. 1011 molecules of .alpha.-bungarotoxin; binding sites were restricted to the end-plate region. Neither acute denervation nor acute poisoning with botulinum toxin altered the number or distribution of .alpha.-bungarotoxin binding sites. In chronically denervated hemidiaphragms, there was an increase in .alpha.-bungarotoxin binding sites (maximum about 5.7 .times. 1012); these sites were distributed across the muscle surface. In chronically poisoned hemidiaphragms, there was also an increase in the number (maximum about 4.7 .times. 1012) and distribution of binding sites. Chronic denervation and chronic botulinum toxin treatment both produced supersensitivity to acetylcholine. At maximal sensitivity, the respective ED50 values were: denervated muscle, 1.1 .times. 10-6 M; botolinum toxin-treated muscle, 5.0 .times. 10-6 M. The combination of denervation plus botulinum toxin treatment did not have additive or synergistic effects on .alpha.-bungarotoxin binding (4.9 .times. 1012 molecules/hemidiaphragm) or on tissue sensitivity to acetylcholine (ED50 = 2.1 .times. 10-6 M). Denervation and botulinum toxin apparently have rather similar effects on the number and distribution of acetylcholine receptors in rat hemidiaphragm.

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