Effects of aminoglycoside antibiotics on the neuromuscular junction: Part I.
The effects of aminoglycoside antibiotics (AGA) including streptomycin (SM), kanamycin (KM), gentamicin (GM), dibekacin (DKB), amikacin (AMK) and sisomycin (SISO), on the neuromuscular junction were studied by in vivo and in vitro experiments. In in vitro experiments, no effect of AGA on rat phrenic nerve diaphragm preparations was observed, but the use of the antibiotics at a high concentration exerted a slight blocking effect on the neuromuscular junction. The blocking effect of SISO and DKB on the neuromuscular junction was marked. These antibiotics were definitely found to compete with eserine in terms of the blocking effect on the neuromuscular junction, but did not compete with calcium chloride. In in vitro experiments with frog sciatic nerve and musculus sartorius preparations, DKB and SISO exerted a blocking effect on the NMJ, inducing the disappearance of action potentials and the appearance of endplate potentials (EPPs). In in vitro experiments with the preparations from Rana catesbiana frogs, SM, GM, DKB and SISO exhibited an inhibiting effect on the release of acetylcholine (ACh), a chemical neurotransmitter in neuromuscular junction, resulting in a decrease in the frequency of miniature endplate potentials (mEPPS). In in vivo experiments with rabbit sciatic tibialis anterior muscle preparations, SM, GM, DKB and SISO exerted a blocking effect on the neuromuscular junction. From the facts that the effect was augmented by the use of magnesium chloride combined with these antibiotics and that the antibiotics competed with calcium chloride and potassium chloride in terms of the blocking effect on the neuromuscular junction, the effects seemed to be due to the inhibition of ACh release.(ABSTRACT TRUNCATED AT 250 WORDS)
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Yamada
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Kuno
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Iwanaga
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001905:Botulinum Toxins / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D015636:Magnesium Chloride; D008297:Male; D009045:Motor Endplate / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D010791:Phrenic Nerve / Q000187:drug effects; D010830:Physostigmine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D011898:Ranidae; D051381:Rats; D011919:Rats, Inbred Strains
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D015636:Magnesium Chloride; D011189:Potassium Chloride; D010830:Physostigmine; D001905:Botulinum Toxins; D008274:Magnesium; D000109:Acetylcholine; D002118:Calcium