The Pyloric Sphincteric Cylinder in Health and Disease

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Chapter 9 (page 38)

The pharmacology of morphia probably provides the best clue as to the role of enkephalins. Morphia acts by increasing muscle tone, delaying gastric emptying and slowing intestinal transit. In the gastrointestinal tract enkephalins may act in a similar manner; gastrointestinal enkephalins may aid in the control of intestinal motility, whereas brain enkephalins are thought to be involved in pain tolerance.

Konturek et al. (l978, l980) determined the effects of enkephalin on the gastrointestinal tract in canines. The results showed that enkephalin mimicked most of the motor effects of opiates; following administration there was a decrease in the rate, but increase in the amplitude of gastric contractions, with a delay in gastric emptying. In the small bowel enkephalin caused a marked reduction in postprandial spike potential activity, and conversion of the fed pattern of activity to a fasting pattern. Intra-arterial enkephalin and morphia increased intraluminal pressure values dose dependently, and decreased mesenteric vascular resistance.


Bishop et al (l986) showed that galanin immunoreactivity was localized exclusively to neuronal elements in the walls of the gastrointestinal tract in the rat, pig and man, and that it occurred at all levels of the tract. Galanin immunoreactive neuronal cells were noted in the submucous plexuses and immunoreactive nerves were present in all layers of the wall, with the possible exception of the mucosa; most fibres were located in the muscle layers. In the human stomach galanin immunoreactive nerves were equally numerous in the "antrum" and fornix. Preliminary pharmacological experiments showed that galanin caused smooth muscle contractions in the rat intestine and induced mild hyperglycaemia (Bishop et al. l986); it appeared to act as a regulatory factor in the control of gastrointestinal motility.

A close relationship existed between galanin and VIP immunoreactivity, both peptides occurring in the same ganglion cells of the submucous plexuses. The distribution of galanin and VIP immunoreactive nerves in the walls of the gastrointestinal tract was also similar, with the following exceptions: galanin fibres were infrequent in the mucosal layer as compared with VIP fibres, which formed dense mucosal plexuses; and galanin nerves did not appear to be associated with the vascular system of the gastrointestinal tract. (Bishop et al. 1986).


According to Buchan et al. (l977) the neurotensin secreting N cell is a typical endocrine cell with a connection to the lumen via microvilli and electron dense secretory granules grouped at the basement membrane. Radioimmunoassay and immunocytochemistry of fresh surgical and endoscopic samples showed that the highest concentration of neurotensin occurs in ileal mucosa, with significant amounts in the jejunum and only traces in the pyloric mucosal zone and duodenum. The concentration of neurotensin in plasma rises after a meal, but its function is still unclear. In the belief that it is a modulator of secretory and motor functions of the stomach, Blackburn et al (l980) infused it intravenously into healthy volunteers at a dose of 2.4 pmol/kg/min, designed to mimic postprandial levels. It was found that neurotensin caused significant inhibition of pentagastrin stimulated gastric acid and pepsin secretion. It also caused significant delay in gastric emptying, making it one more candidate for the hormone postulated to be released from the small intestine and to cause a feedback delay in gastric emptying.


Although individual variations in the distribution of APUD cells in the gastrointestinal tract exist, it is generally agreed that the highest density of gastrin producing G cells occurs in the distal 3.0cm of the stomach, i.e. in that part of the pyloric mucosal zone which lines the sphincteric cylinder. The number gradually decreases in an orad direction until the junctional zone between pyloric and oxyntic mucosa is reached, where a marked decrease in numbers occurs. The first part of the duodenum contains a fifth to an eighth of the number of G cells in the distal stomach. The physiological effects of gastrins, and the sequelae of overproduction in gastrinomas, are well known and need no recapitulation. In a small series of cases of gastric carcinoma Stave and Brandtzaeg (l978) found that the density of G cells increased from the proximal to the distal part of the "antrum", as in normal subjects. In acid corrosive injury to the gastric mucosa damage of G cells may produce histamine-fast achlorhydria, occurring as part of a delayed gastric syndrome (Chap. 39).

In the stomach somatostatin occurs mainly in the pyloric and oxyntic, and not in the cardiac mucosal zones.

Vasoactive intestinal peptide has a predominantly neural localization in the gastrointestinal tract. A dense VIP containing nerve supply occurs around glands in the pyloric and oxyntic mucosal zones; in the duodenum VIP is encountered in neuronal elements between the lobules of Brunner's glands. A particularly rich supply of VIP nerves occurs in structures believed to exert a sphincteric function, a factor which may assist in anatomically defining a sphincter. To the best of our knowledge this finding has not yet been utilized to determine the exact roles of the pyloric ring and pyloric sphincteric cylinder in the mechanism at the pylorus.

Substance P-containing nerve fibres in the gastrointestinal tract occur in highest density in the duodenal villi, muscularis mucosae, blood vessels, Meissner's plexuses and between the lobules of Brunner's glands. In the stomach these fibres have been found to be numerous and interconnecting in the "antrum" 3.0 cm proximal to the pyloric aperture. This is the region of the left pyloric loop in man; whether the occurrence is of any significance in relation to the sphincteric cylinder is not known. Substance P fibres are much less prominent in the upper part of the stomach.

In the gastrointestinal tract enkephalin occurs in highest concentration in the pyloric mucosal zone. Like morphia it causes a decrease in rate, but increase in amplitude of gastric contractions, with delay in emptying. Its effect on cyclical contractions of the sphincteric cylinder has not been determined; it is surmized that it will be of a similar nature.

Galanin immunoreactive fibres are equally numerous in the "antrum" and fornix; the peptide causes smooth muscle contractions and appears to act as a regulatory factor in motility.

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