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Physiological and pathophysiological regulation of ECL-cell activity

Lundgren, Maria LU (2006)
Abstract
The ECL cells are endocrine/paracrine cells located in the acid-producing part of the stomach. They produce and secrete histamine and chromogranin A-derived peptides in response to circulating gastrin. Mobilized histamine stimulates acid secretion from adjascent parietal cells.



The aims of the present investigation were to assess the usefulness of gastric submucosal microdialysis in studies of ECL-cell histamine mobilization in vivo and in studies of how ECL cells respond to different physiological and pathophysiological stimuli.



We found microdialysis to be a reliable method to study ECL-cell histamine mobilization in awake animals. The inflammatory reaction to the probe was moderate and did not seem... (More)
The ECL cells are endocrine/paracrine cells located in the acid-producing part of the stomach. They produce and secrete histamine and chromogranin A-derived peptides in response to circulating gastrin. Mobilized histamine stimulates acid secretion from adjascent parietal cells.



The aims of the present investigation were to assess the usefulness of gastric submucosal microdialysis in studies of ECL-cell histamine mobilization in vivo and in studies of how ECL cells respond to different physiological and pathophysiological stimuli.



We found microdialysis to be a reliable method to study ECL-cell histamine mobilization in awake animals. The inflammatory reaction to the probe was moderate and did not seem to affect the mobilization of histamine.



Gastrin is the main stimulus of the ECL cells. Hypergastrinemia (induced by daily treatment with the proton pump inhibitor omeprazole) raised the microdialysate histamine concentration, an effect that could be prevented by gastrin receptor blockade. Long-term hypergastrinemia led to a reduced ability of the ECL cells to respond to gastrin, perhaps due to changes in the ligand-binding affinity of the gastrin receptor.



A range of hormones, catecholamines, neuropeptides and inflammatory mediators were found to participate in controlling the activity of ECL cells in situ, exerting stimulatory (gastrin, cholecystokinin, pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide, peptide YY, met-enkefalin, endothelin, noradrenaline, adrenaline) or inhibitory (calcitonin gene-related peptide, galanin, somatostatin, prostaglandin E2) actions.



The massive but transient histamine response to PACAP was studied in detail. The short duration of the response was found to be secondary to PACAP receptor desensitization or to depletion of a PACAP-specific pool.



We also studied histamine and pancreastatin mobilization in response to ischemia (clamping of the celiac artery or microinfusion of vasoconstrictors such as endothelin, adrenaline, vasopressin). Ischemia was found to cause tissue hypoxia, mucosal damage and prompt mobilization of large amounts of histamine during a short period of time without affecting the microdialysate pancreastatin concentration. A histamine response without concomitant pancreastatin release may suggest that ischemia triggers the mobilization of ECL-cell histamine by a non-exocytotic release mechanism. (Less)
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author
supervisor
opponent
  • Professor Sandvik, Arne K., Norvegian University of Science and Technology
organization
publishing date
type
Thesis
publication status
published
subject
keywords
pharmacy, toxicology, Pharmacological sciences, pharmacognosy, Gastroenterologi, endothelin, gastrin, ischemia-reperfusion, Physiology, Fysiologi, Gastro-enterology, pancreastatin, histamine, microdialysis, ECL-cell, stomach, Farmakologi, farmakognosi, farmaci, toxikologi
pages
148 pages
publisher
Institute of Experimental Medical Sciences
defense location
GK lecture hall, BMC, Sölvegatan 19
defense date
2006-01-19 09:15:00
ISBN
91-85481-34-3
language
English
LU publication?
yes
additional info
P Ericsson, P Norlén, M Bernsand, P Alm, P Höglund and R Håkanson. 2003. ECL cell histamine mobilization studied by gastric submucosal microdialysis in awake rats: Methodological considerations. Pharmacol Toxicol, vol 93 pp 57-65.
T Konagaya, M Bernsand, P Norlén and R Håkanson. 2001. Mobilization of ECL-cell histamine in response to short- or long-term treatment with omeprazole and/or YF476 studied by gastric submucosal microdialysis in conscious rats. Br J Pharmacol, vol 133 pp 37-42.
P Norlén, M Bernsand, T Konagaya and R Håkanson. 2001. ECL-cell histamine mobilization in conscious rats: effects of locally applied regulatory peptides, candidate neurotransmitters and inflammatory mediators. Br J Pharmacol, vol 134 pp 1767-1777.
M Bernsand, R Håkanson and P Norlén. . Tachyphylaxis of the ECL-cell histamine response to PACAP: Depletion or desensitization? (manuscript)
M Bernsand, P Ericsson, M Björkqvist, C-M Zhao, R Håkanson and P Norlén. 2003. Submucosal microinfusion of endothelin and adrenaline mobilizes ECL-cell histamine in rat stomach, and causes mucosal damage: a microdialysis study. Br J Pharmacol, vol 140 pp 707-717.
M Kitano, M Bernsand, Y Kishimoto, P Norlén, R Håkanson, Y Haenuki, M Kudo and J Hasegava. 2005. Ischemia of the rat stomach mobilizes ECL-histamine. Am J Physiol, vol 288 pp G1084-G1090.
M Bernsand, R Håkanson and P Norlén. . Ischemia mobilizes histamine but not pancreastatin from rat stomach ECL cells. (manuscript)
id
5b20705c-c7d2-4e6a-a3ca-dedb74efd9f5 (old id 546267)
date added to LUP
2016-04-01 16:53:09
date last changed
2018-11-21 20:44:57
@phdthesis{5b20705c-c7d2-4e6a-a3ca-dedb74efd9f5,
  abstract     = {{The ECL cells are endocrine/paracrine cells located in the acid-producing part of the stomach. They produce and secrete histamine and chromogranin A-derived peptides in response to circulating gastrin. Mobilized histamine stimulates acid secretion from adjascent parietal cells.<br/><br>
<br/><br>
The aims of the present investigation were to assess the usefulness of gastric submucosal microdialysis in studies of ECL-cell histamine mobilization in vivo and in studies of how ECL cells respond to different physiological and pathophysiological stimuli.<br/><br>
<br/><br>
We found microdialysis to be a reliable method to study ECL-cell histamine mobilization in awake animals. The inflammatory reaction to the probe was moderate and did not seem to affect the mobilization of histamine.<br/><br>
<br/><br>
Gastrin is the main stimulus of the ECL cells. Hypergastrinemia (induced by daily treatment with the proton pump inhibitor omeprazole) raised the microdialysate histamine concentration, an effect that could be prevented by gastrin receptor blockade. Long-term hypergastrinemia led to a reduced ability of the ECL cells to respond to gastrin, perhaps due to changes in the ligand-binding affinity of the gastrin receptor.<br/><br>
<br/><br>
A range of hormones, catecholamines, neuropeptides and inflammatory mediators were found to participate in controlling the activity of ECL cells in situ, exerting stimulatory (gastrin, cholecystokinin, pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide, peptide YY, met-enkefalin, endothelin, noradrenaline, adrenaline) or inhibitory (calcitonin gene-related peptide, galanin, somatostatin, prostaglandin E2) actions.<br/><br>
<br/><br>
The massive but transient histamine response to PACAP was studied in detail. The short duration of the response was found to be secondary to PACAP receptor desensitization or to depletion of a PACAP-specific pool.<br/><br>
<br/><br>
We also studied histamine and pancreastatin mobilization in response to ischemia (clamping of the celiac artery or microinfusion of vasoconstrictors such as endothelin, adrenaline, vasopressin). Ischemia was found to cause tissue hypoxia, mucosal damage and prompt mobilization of large amounts of histamine during a short period of time without affecting the microdialysate pancreastatin concentration. A histamine response without concomitant pancreastatin release may suggest that ischemia triggers the mobilization of ECL-cell histamine by a non-exocytotic release mechanism.}},
  author       = {{Lundgren, Maria}},
  isbn         = {{91-85481-34-3}},
  keywords     = {{pharmacy; toxicology; Pharmacological sciences; pharmacognosy; Gastroenterologi; endothelin; gastrin; ischemia-reperfusion; Physiology; Fysiologi; Gastro-enterology; pancreastatin; histamine; microdialysis; ECL-cell; stomach; Farmakologi; farmakognosi; farmaci; toxikologi}},
  language     = {{eng}},
  publisher    = {{Institute of Experimental Medical Sciences}},
  school       = {{Lund University}},
  title        = {{Physiological and pathophysiological regulation of ECL-cell activity}},
  year         = {{2006}},
}