Among a variety of adverse effects of antibiotics reported, the neuromuscular blockade, frequently occurred in aminoglycosides, polymyxins, lincomycin and tetracyclines, is one of a serious clinical problem.
The effects of antibiotics on somatic neuromuscular transmission have been extensively studied, however, only limited reports are available on the neuroeffector transmission in gastrointestinal smooth muscle.
Since no one hypothesis accounts successfully for the antibiotics induced gastrointestinal disturbance, alteration of motility, which causes proliferation of Clostridium difficile, is considered one of plausible factors in antibiotic-associated colitis.
Present study was undertaken to investigate the mode of action of antibiotics on the gastrointestinal muscles in guinea pig with special reference to calcium and acetylcholine release.
Guinea pig, weighing 400~700g, was sacrificed and the ileum was isolated. The ileal strip was placed in temperature controlled (37℃) muscle chamber containing Tyrode´s. solution and recorded its motility with Grass Polygraph (Model 7) via force displacement transducer (FT. 03, Grass).
The ileal motility was elicited by acetylcholine, histamine or electric field stimulation, and the effect of antibiotics and/or calcium or phentolamine was observed.
The result obtained are as follows:
1. Acetylcholine (10^7M to 10^6M) and histamine (10^7M to 3 x 10^6M) evoked dose dependent increase in contractile tons of isolated guinea pig ileum.
2. Acetylcholine-induced ileal motility was profoundly. inhibited by colistin, tetracycline, erythromycin and cephaloridine in decreasing order but penicillin, cephalexin, streptomycin and kanamycin were less effective in inhibiting the ileal motility.
3. Histamine-induced ileal motility was strongly inhibited by colistin, cephaloridine, erythromycin, tetracycline and penicillin in decreasing orders, but cephalexin had no influence on the ileal motility.
4. Electric field stimulation-induced ileal motility was completely blocked by tetrodotoxin (5x10-6M) or atropine (10-6M).
5. Colistin, streptomycin and kanamycin markedly suppressed the electric field stimulatc-
dileal motility, but inhibition by pencillin and cephaloridine was less significant.
6. Calcium at high concentration abolished the suppre3sion of intestinal motility by strepto-
mycin but phentolamine was little effective on the antibiotics-induced inhibition of the motility. From these results it is suggested that kanamycin and streptomycin inhibit intestinal
motility by causing inhibition of calcium-dependent acetylcholine release, however, the effects of cephaloridine, erythromycin, tetracycline and Colistin are non-specific and penicillin inhibits only histamine response.
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