Effects of Trimebutine (TMB) on Spontaneous Electrical Activity and on Junction Potentials Evoked by Parasympathetic Nerve Stimulation in Cat and Rabbit Colon

Abstract

Most of the drugs which affect intestinal motility increase the activity of excitatory or inhibitory nerves controlling smooth muscle contractions (i.e. cholinergic or adrenergic nerves). TMB being a drug which modulates colonic motility, we have attempted to determine the modifications of electrical activity underlying the motor effects of this drug. The experiments have been carried out on cat colon and on rabbit proximal colon, on anaesthetized animals and in vitro. Electrical activity was recorded with extracellular pressure electrodes. Parasympathetic efferent nerve fibres were excited by stimulation of the pelvic nerves in the cat, and the vagus nerves in the rabbit. The effects of TMB remained unaffected by adrenergic blocking agents (phentolamine, propranolol, guanethidine) excluding any participation of sympathetic nerves. The action of TMB (0.5 to 2mg/kg in vivo; 10⁻⁶ to 10⁻⁵ Min vitro) consisted in vivo as well as in vitro of an initiation or of an increase of spike potential activity lasting 10–20 minutes (8 animals). Spike activity was potentialized by atropine (0.1mg/kg for the cat; 2 to 3mg/kg for the rabbit; 10⁻⁶M in vitro for both species). Moreover, in the cat under atropine, spike activity became cyclical, i.e. bursts of spikes were interrupted by periods of electrical silence. In the cat, TMB induced a significant decrease in the excitatory junction potential (EJP) amplitude (9 animals). In order to record inhibitory junction potentials (IJPs) without EJPs, experiments were performed under atropine. Under these conditions, TMB induced rhythmic variations in the amplitude of IJPs for 30 to 40 minutes (2 animals). In the rabbit under TMB, EJPs were enhanced (7 animals), whereas IJP amplitude was decreased (6 animals). These variations were statistically significant. All the effects of TMB on spontaneous activity as well as on junction potentials are very similar to those observed, in a previous work, with morphine and enkephalins (1). The effects of TMB were antagonized by naloxone (2mg/kg in vivo 10⁻⁶M in vitro). These results strongly suggest that the action of TMB would be mediated through opiate receptors presumably located on intramural neurones (1). Thus it can be hypothesized that the atropine-resistant excitatory effects of TMB on spike activity would be due to an activation of intramural non-cholinergic excitatory neurones.