The release of 5‐hydroxytryptamine in relation to pressure exerted on the intestinal mucosa

Abstract

In a recent investigation (Biilbring & Lin, 1958) it was found that small amounts of 5-hydroxytryptamine (5-HT) were continuously released into the lumen of an isolated loop of intestine. The quantity released was directly related to the height of intraluminal pressure. Experiments carried out to ascertain whether 5-HT was liberated as a result of pressure on the mucosa, or as a result of peristaltic activity which was evoked by raising the pressure, were not entirely conclusive. When peristaltic activity was abolished either by blocking mucosal sensory receptors with procaine, or by blocking intramural ganglia with hexamethonium, the correlation between pressure and 5-HT release was still observed. However, the extent to which 5-HT release was augmented on raising the intraluminal pressure was less. It was therefore concluded that muscular activity contributed to the mechanism releasing 5-HT, probably by causing, during a peristaltic wave, a considerable additional rise in pressure on the mucosa.The present work was carried out in order to investigate further the mechanism of 5-HT release. METHODS Experiments in vivoGuinea-pigs were used throughout. The animal was anaesthetized by an intravenous injection of a mixture of 0.6% chloralose + 10% urethane (5 ml./kg). One hour after the injection the abdomen was opened and a piece of ileum close to the caecum, 5-7 cm long, was cannulated at both ends. Tyrode solution was passed through the lumen as in the method described by Biilbring & Lin (1958) for isolated loops of intestine. The fluid flowed from a Marriotte bottle, the height of which could be changed, through a narrow tube at a slow rate into the oral end of the intestine. This was connected to a vertical glass tube acting as a water manometer, the pressure being recorded, by air transmission, with a float recorder. The caudal end of the intestine was connected to a T-piece, one arm of which led to a valve. As a rubber valve constituted a certain resistance we used a float valve made of Perspex, as shown in Fig. 1. Fluid entered at A and lifted the conical Perspex float, which was, however, held in a vertical position by the side arm projecting across the tube. The fluid left the tube from the side arm B. The height of the water column in the tube was maintained by the outlet of the syphon tube. 5-HT RELEASE BY INTESTINAL PRESSURE 19When the side arm of the T-piece was closed fluid flowed only as a result of active peristaltic propulsion. In the absence of peristalsis fluid was collected from the side arm of the T-piece. The animal lay on its back and the cut edges of the body wall were lifted up to make a pool. The whole abdominal cavity with the perfused loop of intestine covered by a piece of muslin was bathed by a continuous drip of Tyrode solution at 370 C. Though the two cannulae were held rigidly, the intestine was not stretched between them and could move freely.Experiments in vitro A few experiments were carried out on isolated loops of intestine using the method described by Bilbring & Lin (1958)...

The effects of granisetron, ICS 205–930 and ondansetron on the visceral pain reflex induced by duodenal distension

“…This observation is in marked contrast to the effects of granisetron or ICS 205-930 and conflicts with the potent ability of this compound to antagonize the Bezold-Jarisch reflex in anaesthetized rats (ID50 against 2-methyl-5-HT = 0.4pgkg-, i.v., Butler et al, 1988; ID50 against 5-HT = 3.6,ugkg-1, i.v., Sanger, 1990) (Sanger & Nelson, 1988). If granisetron and ICS 205-930 act by antagonizing a 5-HT receptor, this may be present on the peripheral afferent nerve fibres, being activated by 5-HT released from enterochromaffin cells by distension (Bulbring & Crema, 1959). Alternatively, they may also act within the central nervous system or spinal cord.…”

“…It has been shown that 5-hydroxytryptamine (5-HT) can be released by increasing the intraluminal pressure of the small intestine (Bulbring & Crema, 1959;Burks & Long, 1966). A potential role of endogenous 5-HT in modulating distension-induced reflexes was therefore examined by use of the selective 5-HT3 receptor antagonists granisetron (BRL 43694;Sanger & Nelson, 1989), (Richardson et al, 1985) and ondansetron (GR 38032F; Butler et al, 1988).…”

5-hydroxytryptamine strongly inhibits fluid secretion in guinea pig pancreatic duct cells

“…Mechanical distension of the intestinal mucosa and a variety of neurohormonal stimuli have been shown to release 5-HT from the EC cells mainly into the interstitial space (3), but also into the gut lumen (4, 5). The released 5-HT binds various subtypes of 5-HT receptors on enteric neurons, smooth muscle cells, and epithelial cells and regulates intestinal fluid transport and peristalsis (2,4,6).In the pancreas, 5-HT is mainly present in β cells of the islet of Langerhans (7,8) and in serotonergic pancreatic nerve fibers (2, 9). The presence of the EC cells in the exocrine pancreas has also been noticed but their exact localization and function have not been described (8).…”

Immuno-electron Microscopic Demonstration of Luminal Release of Serotonin from Enterochromaffin Cells of Rat Embryo.

“…The mechanism of luminal release of 5HT has been studied more extensively in the adult animals but scarcely in the developing animals. In adult animals, the luminal release of 5HT is affected by various stimuli such as cholinergic or adrenergic mechanism [1,2] or high intraluminal pressure [4]. However the functional significance of luminally released 5HT is only poorly understood.…”