Fluoroquinolone‐Induced Motor Changes in the Guinea‐Pig Isolated Ileum

Abstract

Abstract:The effects of norlloxacin and enoxacin were examined on spontaneous motor activity in the guinea-pig isolated ileum. Micromolar concentrations of both compounds caused a biphasic response consisting of relaxation followed by transient contraction. Relaxation to noriloxacin, which was unaffected by phentolamine, propranolol and hyoscine (each at 1 pM), was partially sensitive to tetrodotoxin (1 pM). This indicates that the response is partly mediated by nonadrenergic non-cholinergic (NANC) inhibitory nerves, and partly related to a direct action on the smooth muscle. Apamin (0.1 pM) and suramin (300 pM) inhibited norfloxacin-induced relaxations to an extent similar to that of tetrodotoxin. Conversely, NG-nitro-L-arginine (300 pM) was ineffective. In the presence of theophylline (100 pM) and 3-isobutyl-lmethylxanthine (1 0 pM), norfloxacin caused relaxation less effective than when added alone. Based on this observation, the NANC component of the relaxation apparently depends on ATP release, whereas the direct component might be due, at least in part, to phosphodiesterase inhibition. Norfloxacin-induced contractions were neurogenic and cholinergic in nature. They were reduced by indomethacin or S-ketoprofen (both at 0.01-1 pM) and suramin (300 pM), suggesting involvement of local prostaglandin production probably induced by ATP release. Previous findings revealed that norfloxacin acted as a non-competitive antagonist at enteric GABAA receptors. In this study the same property was shared by enoxacin against the contractile response to 3-aminopropane sulphonic acid (3-APS), a GABAA receptor agonist. In conclusion, fluoroquinolones exert inhibitory and excitatory effects in the guinea-pig ileum. These are mediated by ATE prostaglandin and acetylcholine release that might underlie, at least in part, the alterations of gastrointestinal motility observed after fluoroquinolone administration. Furthermore, isolated intestinal preparations might be useful to predict the GABAA-antagonist potential of this class of compounds.

Modulatory effect of three antibiotics on uterus bovine contractility in vitro and likely therapeutic approaches in reproduction

“…In agreement with the previous studies of other fluoroquinolones [36,51], we believe that enrofloxacin acts even in the uterus such as GABA A antagonist, blocking the ATP-dependent potassium channels [36][37][38]41,[50][51][52]. In support of this, the stimulatory action of enrofloxacin on uterine contractility, measured in our experiment, was higher in the luteal phase, the concentration of the GABA A receptor in uterine tissue [70].…”

“…In addition, fluoroquinolones induce the release of PGF2a in guinea-pig ileum [38], which are responsible for cholinergic transmission in the myenteric plexus [53,54]. Moreover, in vitro studies on rat's myometrium have reported that danofloxacin has a biphasic dose-related effect on uterine contractility induced by oxytocin.…”

“…Other studies on smooth muscles of different organs and animal species have reported that fluoroquinolones act as antagonists of the GABA receptor by blocking the ATP-dependent potassium channels [36][37][38]41,[50][51][52]. In addition, fluoroquinolones induce the release of PGF2a in guinea-pig ileum [38], which are responsible for cholinergic transmission in the myenteric plexus [53,54].…”

“…Moreover, the antibiotics, such as penicillins and quinolones, can also affect the oxidative state of the organism and the production of reactive oxygen species [30][31][32][33][34]. Several studies have reported that antibiotic therapy is able to directly modulate the contractility of smooth muscles [35][36][37][38][39] also. However, this effect is subject to changes attributed to the species, tissue, or organ under examination [38][39][40][41].…”

“…Several studies have reported that antibiotic therapy is able to directly modulate the contractility of smooth muscles [35][36][37][38][39] also. However, this effect is subject to changes attributed to the species, tissue, or organ under examination [38][39][40][41]. For example, the erythromycin is able to stimulate the contraction of smooth muscle cells of the stomach and duodenum, probably by acting on the receptors of motilin [42,43] and moreover, seems to determine an increase in the amplitude and frequency of contraction even in rat's myometrium; the effect probably mediated by histamine H 1 receptors and calcium channels [44].…”