Effects of Enkephalins and Morphine on Spontaneous Electrical Activity and on Junction Potentials Elicited by Parasympathetic Nerve Stimulation in Cat and Rabbit Colon

Abstract

The effects of Leu‐enkephalin, Met‐enkephalin and morphine on excitatory junction potentials (e.j.ps) and inhibitory junction potentials (i.j.ps) elicited by stimulation of efferent parasympathetic nerves were studied in cats and rabbits, anaesthetized and in vitro. Enkephalins (0.008 mg/kg in vivo and 10−6m in vitro) enhanced e.j.p. amplitude in rabbit proximal colon and decreased it in rabbit distal colon and in cat colon. Enkephalins decreased i.j.p. amplitude in all the three models. Morphine (0.2 mg/kg in vivo and 10−6m in vitro) had the same effects as enkephalins on e.j.ps. In contrast, morphine decreased i.j.p. amplitude in rabbit proximal and distal colon and increased it in cat colon. Enkephalins and morphine induced (especially in the cat) spike activity which was potentiated by atropine (0.1 mg/kg in vivo or 10−6m in vitro). All the effects of enkephalins and morphine were antagonized by naloxone (0.2 mg/kg in vivo or 10−6m in vitro). These results suggest that the facilitatory effects of enkephalins and morphine on e.j.ps of rabbit proximal colon are due to the absence of opiate receptors on the excitatory nerve pathway and to a removal of inhibition by blockade of the non‐adrenergic, non‐cholinergic inhibitory pathway. Enkephalinergic intramural neurones may modulate the activation of either excitatory or inhibitory pathways in intramural reflexes.

Effects of morphine on electrical activity of the rectum in man.

“…These results are in keeping with those obtained on cat colon by Blanquet et al (1982). In addition, the increase in motility observed immediately after morphine administration in dog small intestine in vivo and rat colon in vitro remained unchanged when atropine was present (Plant & Miller, 1926;Gillan & Pollock, 1980).…”

“…As previously shown in the cat (Blanquet et al 1982), the spiking activity produced by morphine often exhibits periodicity. In man, a cyclical increase in pressure induced in the sigmoid colon by morphine has also been noted (Painter & Truelove, 1964).…”

“…However, the possibility that the thoracolumbar sympathetic centre innervating the rectum (Netter, 1962) may participate cannot be excluded, since none of the patients had a complete lesion of this centre. Nevertheless, it may reasonably be hypothesized that similar effects to those demonstrated in animals (Blanquet et al 1982) may also take place at the periphery in man. Morphine cannot have had any direct effect on smooth muscle cells since it failed to excite an aganglionic rectum in a patient with Hirschsprung's disease.…”

“…Opiates modify gut motility by acting on the central nervous system (see Porreca, Galligan & Burks, 1986) as well as on the enteric nervous system (Paton, 1957; Wood, 1980;Blanquet, Bouvier & Gonella, 1982; see also North, 1982). In various species, enkephalinergic innervation has been detected in the intramural nervous system of various portions of the gut (Furness, Costa, Franco & Llewellyn-Smith, 1980;Schultzberg, Hokfelt, Nilsson, Terenius, Rehfeld, Brown, Elde, Goldstein & Said, 1980;Bouvier, Kirschner & Gonella, 1986).…”

[Met5]enkephalin acts via δ‐opioid receptors to inhibit pelvic nerve‐evoked contractions of cat distal colon

“…Enkephalin-like immunoreactivity has been shown within both sacral preganglionic neurones (Glazer & Basbaum, 1980) and neurones ofthe colonic myenteric plexus (see above). Furthermore, enkephalins inhibit pelvic nerve-evoked excitatory postsynaptic potentials in parasympathetic colonic neurones (Kennedy & Krier, 1987a,b) and excitatory junction potentials in this tissue (Blanquet et al, 1982). Thus, endogenous enkephalins may be important modulators of motor activity of the colon.…”