Effects of Aminoglycoside Antibiotics on Cholinergic Autonomic Nervous Transmission

Abstract

The effects of eight aminoglycoside antibiotics, gentamicin, neomycin B, ribostamycin, dibekacin B, kanamycin A, streptomycin, tobramycin and amikacin, and two non-aminoglycoside antibiotics, tetracycline and ampicillin, on cholinergic autonomic nervous transmission were studied using isolated guinea-pig ileum preparation. The aminoglycoside antibiotics blocked the transmurally elicited twitches of the ileum in a concentration-dependent manner. The blocking effect of aminoglycosides was biphasic, i.e., an initial reduction followed by a spontaneous partial recovery. Dibekacin was the most potent parasympathetic inhibitor, followed by neomycin B, tetracycline, gentamicin, streptomycin, kanamycin A, tobramycin, ribostamycin, and amikacin. Ampicillin had no blocking effect. The tested antibiotics did not affect acetylcholine (ACh)-induced contraction of the ileum, except for high concentrations of neomycin B, gentamicin, and streptomycin. The three antibiotics shifted the dose-response curves for ACh to the right without affecting the maximal contraction. Naloxon, yohimbine, hexamethonium and choline chloride failed to eliminate the blocking effect of the antibiotics on twitches of the ileum induced by transmural stimulation. However, increase of the extracellular Ca ion concentration virtually abolished the blockade. Dibekacin blocked the evoked but not the spontaneous release of ACh and shifted the dose-response curve of CaCl2-dependent transmurally elicited contractions of the ileum to the right. These results suggest that the site for the block of aminoglycosides is mainly the cholinergic nerve terminal, where they reduce the available Ca ions required for the release of ACh.