ECL‐cell histamine mobilization in conscious rats: effects of locally applied regulatory peptides, candidate neurotransmitters and inflammatory mediators

Abstract

1 The ECL cells control gastric acid secretion by mobilizing histamine in response to circulating gastrin. In addition, the ECL cells are thought to operate under nervous control and to be in¯uenced by local in¯ammatory processes. 2 The purpose of the present study was to monitor histamine mobilization from ECL cells in conscious rats in response to locally applied regulatory peptides, candidate neurotransmitters and in¯ammatory mediators. 3 Microdialysis probes were implanted in the submucosa of the acid-producing part of the rat stomach. Three days later, the agents to be tested were administered via the microdialysis probe and their eects on basal (48 h fast) and stimulated (intravenous infusion of gastrin-17, 3 nmol kg 71 h 71 ) mobilization of ECL-cell histamine was monitored by continuous measurement of histamine in the perfusate (radioimmunoassay). 4 Locally administered gastrin-17 and sulfated cholecystokinin-8 mobilized histamine as did pituitary adenylate cyclase-activating peptide-27, vasoactive intestinal peptide, peptide YY, metenkephalin, endothelin and noradrenaline, adrenaline and isoprenaline. 5 While gastrin, sulfated-cholecystokinin-8, met-enkephalin and isoprenaline induced a sustained elevation of the submucosal histamine concentration, endothelin, peptide YY, pituitary adenylate cyclase activating peptide, vasoactive intestinal peptide, noradrenaline and adrenaline induced a transient elevation. 6 Calcitonin gene-related peptide, galanin, somatostatin and the prostanoid misoprostol inhibited gastrin-stimulated histamine mobilization. 7 The gut hormones neurotensin and secretin and the neuropeptides gastrin-releasing peptide, neuropeptide Y and substance P failed to aect ECL-cell histamine mobilization, while motilin and neuromedin U-25 had weak stimulatory eects. Also acetylcholine, carbachol, serotonin and the amino acid neurotransmitters aspartate, g-aminobutyric acid, glutamate and glycine were inactive or weakly active as was bradykinin. 8 In summary, a range of circulating hormones, local hormones, catecholamines, neuropeptides and in¯ammatory mediators participate in controlling the activity of rat stomach ECL cells in situ.

Simultaneous detection of gastric acid and histamine release to unravel the regulation of acid secretion from the guinea pig stomach

“…Although we show that this pathway is active in the guinea pig, no other studies have monitored both the direct and indirect gastrin pathways leading to the activation of the parietal cell in one experiment on any species. However, other studies have shown that when acid secretion is monitored, inhibitors of the gastrin pathway diminish acid secretion (16,20) or when histamine is monitored, gastrin elevates levels of histamine (15,19,23,29). Our data are supportive of both these studies, but provide further information in the degree gastrin plays in both pathways.…”

“…pH sensors and devices offer excellent dynamic information and have shown excellent clinical use (2, 10, 12); however, histamine monitoring is far more difficult. Histamine levels have been monitored at present using microdialysis sampling with either chromatographic or radioimmunoassay analysis (8,23,32,41). These approaches, although they offer excellent sensitivity, are limited by the time scales where data points can be collected.…”

“…Gastric acid has been monitored using simple approaches such as titrations from acid perfusates or using pH sensors (4,10,20,33). Histamine has been widely monitored using radioimmunoassays (9,23,32,41) and chromatographic approaches (22,38) and via mass spectrometry (14,40). These studies have provided insight into the regulation of the ECL and parietal cell, but not the whole mechanism (19,20,39).…”

Transcriptomes of purified gastric ECL and parietal cells: identification of a novel pathway regulating acid secretion

“…ECL cells also express the PYY Y1 receptor, which, on isolated ECL cells, shows inhibition of gastrin-stimulated histamine release (70). However, in situ microdialysis studies showed slight elevation of histamine release in the rat stomach on application of PYY (38). The basis for these controversial results remains to be elucidated but may involve the presence of PYY receptors on cells other than ECL cells, such as the G cell.…”

Effect of humulus lupulus on Gastric Secretion in a Rat Pylorus-Ligated Model

“…[14][15][16][17][18] Moreover, bitter herbs like Swertia Herba or Gentiana Radix are traditionally used as drugs to activate gastric function in Japan. Thus, we hypothesized that the bitterness of hops could be important in inducing gastric secretion, since bitterness is able to induce gastric secretion via the cephalic phase.…”