The effects of acute and chronic botulinum toxin treatment on receptor number, receptor distribution and tissue sensitivity in rat diaphragm.

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 x 10(11) 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 x 10(12); these sites were distributed across the muscle surface. In chronically poisoned hemidiaphragms, there was also an increase in the number (maximum about 4.7 x 10(12)) 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 x 10(-6) M; botulinum toxin-treated muscle, 5.0 x 10(-6) M. The combination of denervation plus botulinum toxin treatment did not have additive or synergistic effects on alpha-bungarotoxin binding (4.9 x 10(12) molecules/hemidiaphragm) or on tissue sensitivity to acetylcholine (ED50 = 2.1 x 10(-6) M). It is concluded that denervation and botulinum toxin have rather similar effects on the number and distribution of acetylcholine receptors in rat hemidiaphragm.

• Authors: L L Simpson
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 200 Issue 2 Pg. 343-51 (Feb 1977) ISSN: 0022-3565 [Print] United States
• PMID: 839441 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Bungarotoxins
• Receptors, Cholinergic
• Botulinum Toxins
• Acetylcholine

Topics

• Acetylcholine (metabolism, pharmacology)
• Animals
• Binding Sites (drug effects)
• Botulinum Toxins (metabolism, pharmacology)
• Bungarotoxins (metabolism)
• Diaphragm (drug effects, innervation, metabolism)
• In Vitro Techniques
• Male
• Muscle Contraction (drug effects)
• Muscle Denervation
• Muscles (drug effects, innervation, metabolism)
• Neuromuscular Junction (drug effects)
• Rats
• Receptors, Cholinergic (drug effects, metabolism)
• Time Factors