INFLUENCE OF ANTIBIOTICS ON THE MECHANICAL RESPONSES OF GUINEA-PIG ILEUM TO ACETYLCHOLINE AND HISTAMINE

INFLUENCE OF ANTIBIOTICS ON THE MECHANICAL RESPONSES OF GUINEA-PIG ILEUM TO ACETYLCHOLINE AND HISTAMINE ¹

Andy Petroianu ²

Júlio Weinberg ³

Petroianu, A. & WEINBERG, J. - Influence of antibiotics on the mechanical responses of guinea-pig ileum to acetylcholine and histamine. . Acta Cir. Bras 13 (3):00-00, 1998.

SUMMARY: The side effects of antibiotics have been extensively described during the last decades, however, their role on digestive motility must be better investigated. Following a line of research, the influence of penicillin, chloranfenicol tetracycline and gentamicine on longitudinal smooth muscle responses to acetylcholine and histamine were studied on guinea-pig ileum. There were no differences between the responses before and after the addition of each antibiotic. Further investigations must be performed in order to find a possible influence of antibiotics on digestive motility.

SUBJECT HEADINGS: Ileum. Motility. Agonists. Smooth muscle. Antibiotics. Acetylcholine. Histamine. Penicillin. Chloranfenicol. Tetracycline. Gentamicine.

INTRODUCTION

During the first decades of the present century, Alvarez and other investigators established some patterns of spontaneous gastrointestinal motility. More recently, many authors demonstrated that several physiologic agonists and pharmacological drugs induce to and/or modify the digestive motility ^2,6 .

Enteric disturbances like cholics and diarrhea are frequently observed in patients using antibiotics. A possible effect of those drugs on bowel responses to physiologic agonists may be related to such symptoms. Considering that acetylcholine (Ach) and histamine (His) are two of the most important digestive agonists ^1,7 , and that penicillin, chloranfenicol, tetracycline and gentamicine are routinely used in the clinical practice, these mediators and antibiotics were assessed in the present paper. This investigation is part of a line of research related to the answer of isolated digestive smooth muscle to physiologic agonists in presence or not of surgical procedures and/or drugs ^3,4,5 .

METHOD

Seromuscular ileal longitudinal strips from 40 adult guinea-pigs of both sexes (34 females and 6 males), with a weight range between 640 and 830 (710 ± 49) grams were investigated. The ileal layer (30 x 2 mm) was mounted in an organ chamber perfused with aerated Tyrode’s solution (NaCl - 8.0 g/l, KCl - 0.2 g/l, CaCl₂ - 0.2 g/l, MgCl₂ - 0.1 g/l, NaH₂PO₄ - 0.05 g/l, NaHCO₃ - 1.0 g/l and glucose - 1.0 g/l) at 37 ^oC ² . Each strip was connected to an auxotonic lever (vertical shift = 4 mm / 100 mg) in order to obtain chemographic records of its mechanical activity.

During the first 30 minutes, the strip was left in rest. No drug or agonist was added to the organ chamber and the nutritive solution was renewed every ten minutes. Then, cumulative dose-response assays were performed with the agonists. Each strip was submitted to two assays with either Ach or His. Following the first assay, a 30 minutes interval was observed before the second assay with the same agonist, to allow complete relaxation of the smooth muscle. During this interval, the nutritive solution was replaced every ten minutes. In each second assay, one single dose of one of the antibiotics listed below was added to the organ chamber immediately before the cumulative addition of the agonist ^3,4,5,8,9 .

Each antibiotic was assayed in ten different ileal strips: five with Ach and five with His. The antibiotics and their final concentrations in the bath solution were: penicillin (penicilina G potássica cristalina - Squibb, Brasil - 100 units / ml), chloranfenicol (cloranfenicol - Vital-Brazil, Brasil - 13 µg / ml), tetracycline (cloridrato de oxitetraciclina - Pfizer, Brasil - 2.5 µg / ml) and gentamicine (sulfato de gentamicina - Schering, Brasil - 9 µg / ml). The drug concentrations were equivalent to the probable extracellular drug concentration found in a 70 kg patient receiving the mean usual clinical dose.

The affinity of the muscle strips for the agonists was calculated through median effective dose (ED-50) from the line adjusted to the experimental data by the least square method ^8,9 . Comparison between each two assay groups of ileal strips for each antibiotic were made using paired t test, with P < 0.05 as the level of significance.

RESULTS

Guinea-pig ileal strips responded to Ach and His. This answer was in a dose-dependent way. The results of the ED-50 for both agonists are shown in Table I.

There were no differences between the control values and those found in presence of each antibiotic.

Table I
- Calculated ED-50 (mean ± standard error of mean in the control group and after addition of antibiotics, in guinea-pig isolated ielum.

	A n t i b i o t i c s	A g o ni s t s
	Acetylcholine (x 10-7 M)	Histamine (x 10-7 M)
Control	2.94 ± 0.64	2.23 ± 0.37
Penicillin	1.39 ± 0.47	0.87 ± 0.02
Chloranfenicol	1.59 ± 0.21	0.60 ± 0.08
Oxytetracycline	0.69 ± 0.11	1.58 ± 0.69
Gentamicine	3.90 ± 1.05	1.98 ± 0.70

DISCUSSION

Ach and His are potent ileal neurotransmitters. Several drugs induce alterations in bowel motility. These disturbances may produce abdominal discomfort, vomiting and diarrhea. Antibiotics may act on smooth muscle motility and provoke mechanical disturbances. Antagonism between calcium and aminoglycosides or tetracycline are well established in the literature ^1,2,6 . However, we were not able to find any effect of the four studied antibiotics on isolated ileal muscle responses to Ach or His.

CONCLUSION

Based on the present investigation, penicillin, chloranfenicol, tetracycline and gentamicine does not seem to affect the mechanical response of ileum to Ach and His, in vitro . We must emphasize that this is a preliminary study and further investigations are necessary to establish a possible effect of antibiotics on the motility of small bowel.

REFERENCES

1. Elmqvist, D.; Josephson, J.O. - The nature of neuromuscular block produced by neomicine. Acta Physiol. Scand., 54: 105-110, 1962.

2. Morais, I.P.; Conrado, A.P.; Kurtz, G.S. - Competitive antagonism between calcium and aminoglycoside antibiotics on guinea-pig intestinal smooth muscle. Arch. Int. Pharmacodyn., 231: 317-327, 1978.

3. Petroianu, A. & Weinberg, J. - Motility of isolated mammalian gastric fundus. Comp. Biochem. Physiol., 85C: 57-59, 1986.

4. Petroianu, A.; Lázaro da Silva, A.; Barbosa, A.J.A. - Gastric fundus morphology and motility after subtotal gastrectomy and gastroduodenal anastomosis in the dog. Med. Sci. Res., 17: 291-293, 1989.

5. Petroianu, A. - The influence of therapeutic drugs on the mechanical responses of the gastric fundus to acetylcholine.

6. Pittinger, G. & Adamsson, R. - Antibiotic blockade of neuromuscular functions. Ann. Rev. Pharmacol., 12: 169-184, 1972.

7. Stubbins, J.F.; Hudgins, P.M. - Sulfhydryl group reagents. Experientia, 27: 669-670, 1971.

8. Van Rossum, J.M. - Cumulative dose-response curves. Arch. Int. Pharmacodyn., 143: 299-330, 1963.

9. Vane, J.R. - A sensitive method for assay of 5 hydroxitryptamine. Br. J. Pharmacol., 12: 344-349, 1957.

PETROIANU, A. & WEINBERG, J. - Influência de antibióticos na resposta mecânica de íleo isolado de cobaia a acetilcolina e histamina. Acta Cir. Bras 13 (3):00-00, 1998.

RESUMO: Os efeitos colaterais dos antibióticos têm sido extensivamente descritos nas últimas décadas, entretanto o seu papel na motilidade digestiva precisa ser melhor pesquisada. Seguindo uma linha de trabalho, avaliou-se a influência da penicilina, do cloranfenicol, da tetraciclina e da gentamicina na resposta muscular lisa longitudinal do íleo de cobaia a acetilcolina e histamina. Não foram encontradas diferenças entre as respostas antes e após a adição de cada um dos antibióticos. Outras investigações necessitam ser realizadas com o objetivo de se verificar uma possível influência dos antibióticos na motilidade digestiva.

DESCRITORES: Íleo. Motilidade. Agonistas. Musculatura lisa. Antibióticos. Acetilcolina. Histamina. Penicilina. Cloranfenicol. Tetraciclina. Gentamicina.

CORRESPONDENCE TO :

Prof. Andy Petroianu

Avenida Afonso Pena, 1626 - apto. 1901

30130-005 Belo Horizonte, MG

PHONE / FAX : [phone]

Accepted for publication march, 1998.

1.Work performed at Departmen of Physiology, Biophisics and Pharmacology of the Biological Sciences Insitut of the Federal University of Minas Gerais. Research supported by CNPq, FAPEMIG and PRPq-UFMG

Work performed at Departmen of Physiology, Biophisics and Pharmacology of the Biological Sciences Insitut of the Federal University of Minas Gerais. Research supported by CNPq, FAPEMIG and PRPq-UFMG

2. Professor of the Department of Surgery of the Medical School of the Federal Unviersity of Minas Gerais, Free Docent of the da Escola Paulista de Medicina - UNIFESP, Free Docent of the Medical School of Ribeirão Preto – University of São Paulo, Research I of CNPq

3. Professor of the Department of Physiology, Biophisics and Pharmacology of the Biological Sciences Institut of the Federal University of Minas Gerais

Publication Dates

• Publication in this collection
  19 Nov 1998
• Date of issue
  July 1998