Effect of Drugs and Electrical Field Stimulation on Circular Muscle Strips From Human Lower Oesophagus

Abstract

SUMMARYSphincteric muscle from human lower oesophagus may be identifiable in vitro by its ability to develop a very high level of tone (sustained resting tension). Circular muscle strips from human lower oesophagus generally behave in a similar manner to strips from the opossum oesophagus with respect to development of tone, responses to electrical field stimulation and responses to a variety of drugs. Pharmacological analysis of responses to field stimulation in strips from the region of the oesophago-gastric junction suggests that thF typical biphasic response (relaxation followed by an after-contraction) is mediated by nerves which are neither adrenergic nor cholinergic. Of the substances examined only vasoactive intestinal peptide (VIP) cannot be excluded as a possible candidate for the role of inhibitory transmitter. The mechanism producing the after-contraction is not clear but it would seem unlikely that this is simply a rebound contraction. The after-contraction can be blocked independently of the relaxation by a variety of agents and is potentiated by metoclopramide.

Regionally dependent neuromuscular functions of motilin and 5‐HT4 receptors in human isolated esophageal body and gastric fundus

“…Together, these data indicate the potential for superior prokinetic activity of prucalopride in the esophagus. Similar activities have previously been reported for non‐selective 5‐HT 4 receptor agonists such as metoclopramide (which potentiated the after‐contractions in human isolated LES circular muscle) and in vivo with the 5‐HT 4 agonist and 5‐HT 2B antagonist tegaserod (which reduced postprandial acid exposure and the number of reflux episodes and transient LES relaxations in patients with abnormal acid exposure, without affecting LES pressure) but not mosapride or cisapride (which had little‐or‐no ability to increase esophageal motor function in patients with GERD). The reasons for the differences in activities between the different 5‐HT 4 receptor agonists are unclear, but in contrast to the selective activity and relatively high intrinsic activity of prucalopride for the 5‐HT 4 receptor, the marked variations in intrinsic activities of these compounds at the 5‐HT 4 receptor and their varied abilities to affect other receptors, means it is difficult to use these data to draw conclusions about the true role of the 5‐HT 4 receptor.…”

Evidence for involvement of nitric oxide in the non‐adrenergic non‐cholinergic (NANC) relaxation of human lower oesophageal sphincter muscle strips

“…The response to EFS was as previously reported (McKirdy & Marshall, 1985) with a predominant relaxation. This relaxation was resistant to 5 /M-guanethidine and to 1 uM-atropine (Fig.…”

“…High concentrations of carbachol also reduce or abolish any component of contraction in the response to EFS (see Fig. 4B, McKirdy & Marshall, 1985).…”

“…Four strips of circular muscle were taken from each specimen. Each strip was set up for isometric recording and subjected to electrical field stimulation (EFS; 0.3 ms pulses at 10 Hz for 5 s) as described in detail previously (McKirdy & Marshall, 1985).…”

Proceedings of the Physiological Society, 18‐19 April 1986, Sheffield Meeting: Poster Communications

“…We have re-examined the effects of catecholamines on human oesophago-gastric junction (OGJ), choledocho-duodenal junction (CDJ), ileo-caecal junction (JCJ) and internal anal junction (IAJ) removed at surgery. Sphincteric muscle has been tentatively identified by its development of tone (sustained resting tension) and a prominent relaxation to electrical field stimulation (EFS) using 0 3 ms pulses at 10 Hz for 5 s (McKirdy & Marshall, 1985 Burleigh, D'Mello & Parks (1979) in 8 out of 9 strips, with one showing relaxation. Response of CDJ to noradrenaline was relaxation in 7 out of 7 strips.…”