Physiological and pathophysiological regulation of ECL-cell activity

Maria Lundgren

Physiological and pathophysiological regulation of ECL-cell activity

Maria Lundgren

Division of Microbiology, Immunology and Glycobiology - MIG

Research output: Thesis › Doctoral Thesis (compilation)

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 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.

Original language	English
Qualification	Doctor
Awarding Institution	Department of Experimental Medical Science
Supervisors/Advisors	Norlén, Per, Supervisor Håkanson, Rolf, Supervisor
Award date	2006 Jan 19
Publisher	Institute of Experimental Medical Sciences
ISBN (Print)	91-85481-34-3
Publication status	Published - 2006

Bibliographical note

Defence details

Date: 2006-01-19
Time: 09:15
Place: GK lecture hall, BMC, Sölvegatan 19

External reviewer(s)

Name: Sandvik, Arne K.
Title: Professor
Affiliation: Norvegian University of Science and Technology

---

<div class="article_info">P Ericsson, P Norlén, M Bernsand, P Alm, P Höglund and R Håkanson. <span class="article_issue_date">2003</span>. <span class="article_title">ECL cell histamine mobilization studied by gastric submucosal microdialysis in awake rats: Methodological considerations.</span> <span class="journal_series_title">Pharmacol Toxicol</span>, <span class="journal_volume">vol 93</span> <span class="journal_pages">pp 57-65</span>.</div>
<div class="article_info">T Konagaya, M Bernsand, P Norlén and R Håkanson. <span class="article_issue_date">2001</span>. <span class="article_title">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.</span> <span class="journal_series_title">Br J Pharmacol</span>, <span class="journal_volume">vol 133</span> <span class="journal_pages">pp 37-42</span>.</div>
<div class="article_info">P Norlén, M Bernsand, T Konagaya and R Håkanson. <span class="article_issue_date">2001</span>. <span class="article_title">ECL-cell histamine mobilization in conscious rats: effects of locally applied regulatory peptides, candidate neurotransmitters and inflammatory mediators.</span> <span class="journal_series_title">Br J Pharmacol</span>, <span class="journal_volume">vol 134</span> <span class="journal_pages">pp 1767-1777</span>.</div>
<div class="article_info">M Bernsand, R Håkanson and P Norlén. <span class="article_issue_date"></span>. <span class="article_title">Tachyphylaxis of the ECL-cell histamine response to PACAP: Depletion or desensitization?</span> (manuscript)</div>
<div class="article_info">M Bernsand, P Ericsson, M Björkqvist, C-M Zhao, R Håkanson and P Norlén. <span class="article_issue_date">2003</span>. <span class="article_title">Submucosal microinfusion of endothelin and adrenaline mobilizes ECL-cell histamine in rat stomach, and causes mucosal damage: a microdialysis study.</span> <span class="journal_series_title">Br J Pharmacol</span>, <span class="journal_volume">vol 140</span> <span class="journal_pages">pp 707-717</span>.</div>
<div class="article_info">M Kitano, M Bernsand, Y Kishimoto, P Norlén, R Håkanson, Y Haenuki, M Kudo and J Hasegava. <span class="article_issue_date">2005</span>. <span class="article_title">Ischemia of the rat stomach mobilizes ECL-histamine.</span> <span class="journal_series_title">Am J Physiol</span>, <span class="journal_volume">vol 288</span> <span class="journal_pages">pp G1084-G1090</span>.</div>
<div class="article_info">M Bernsand, R Håkanson and P Norlén. <span class="article_issue_date"></span>. <span class="article_title">Ischemia mobilizes histamine but not pancreastatin from rat stomach ECL cells.</span> (manuscript)</div>

Subject classification (UKÄ)

Basic Medicine

Free 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

Cite this

@phdthesis{5b20705cc7d24e6aa3cadedb74efd9f5,

title = "Physiological and pathophysiological regulation of ECL-cell activity",

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 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.",

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",

author = "Maria Lundgren",

note = "Defence details Date: 2006-01-19 Time: 09:15 Place: GK lecture hall, BMC, S{\"o}lvegatan 19 External reviewer(s) Name: Sandvik, Arne K. Title: Professor Affiliation: Norvegian University of Science and Technology --- <div class={"}article\_info{"}>P Ericsson, P Norl{\'e}n, M Bernsand, P Alm, P H{\"o}glund and R H{\aa}kanson. <span class={"}article\_issue\_date{"}>2003</span>. <span class={"}article\_title{"}>ECL cell histamine mobilization studied by gastric submucosal microdialysis in awake rats: Methodological considerations.</span> <span class={"}journal\_series\_title{"}>Pharmacol Toxicol</span>, <span class={"}journal\_volume{"}>vol 93</span> <span class={"}journal\_pages{"}>pp 57-65</span>.</div> <div class={"}article\_info{"}>T Konagaya, M Bernsand, P Norl{\'e}n and R H{\aa}kanson. <span class={"}article\_issue\_date{"}>2001</span>. <span class={"}article\_title{"}>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.</span> <span class={"}journal\_series\_title{"}>Br J Pharmacol</span>, <span class={"}journal\_volume{"}>vol 133</span> <span class={"}journal\_pages{"}>pp 37-42</span>.</div> <div class={"}article\_info{"}>P Norl{\'e}n, M Bernsand, T Konagaya and R H{\aa}kanson. <span class={"}article\_issue\_date{"}>2001</span>. <span class={"}article\_title{"}>ECL-cell histamine mobilization in conscious rats: effects of locally applied regulatory peptides, candidate neurotransmitters and inflammatory mediators.</span> <span class={"}journal\_series\_title{"}>Br J Pharmacol</span>, <span class={"}journal\_volume{"}>vol 134</span> <span class={"}journal\_pages{"}>pp 1767-1777</span>.</div> <div class={"}article\_info{"}>M Bernsand, R H{\aa}kanson and P Norl{\'e}n. <span class={"}article\_issue\_date{"}></span>. <span class={"}article\_title{"}>Tachyphylaxis of the ECL-cell histamine response to PACAP: Depletion or desensitization?</span> (manuscript)</div> <div class={"}article\_info{"}>M Bernsand, P Ericsson, M Bj{\"o}rkqvist, C-M Zhao, R H{\aa}kanson and P Norl{\'e}n. <span class={"}article\_issue\_date{"}>2003</span>. <span class={"}article\_title{"}>Submucosal microinfusion of endothelin and adrenaline mobilizes ECL-cell histamine in rat stomach, and causes mucosal damage: a microdialysis study.</span> <span class={"}journal\_series\_title{"}>Br J Pharmacol</span>, <span class={"}journal\_volume{"}>vol 140</span> <span class={"}journal\_pages{"}>pp 707-717</span>.</div> <div class={"}article\_info{"}>M Kitano, M Bernsand, Y Kishimoto, P Norl{\'e}n, R H{\aa}kanson, Y Haenuki, M Kudo and J Hasegava. <span class={"}article\_issue\_date{"}>2005</span>. <span class={"}article\_title{"}>Ischemia of the rat stomach mobilizes ECL-histamine.</span> <span class={"}journal\_series\_title{"}>Am J Physiol</span>, <span class={"}journal\_volume{"}>vol 288</span> <span class={"}journal\_pages{"}>pp G1084-G1090</span>.</div> <div class={"}article\_info{"}>M Bernsand, R H{\aa}kanson and P Norl{\'e}n. <span class={"}article\_issue\_date{"}></span>. <span class={"}article\_title{"}>Ischemia mobilizes histamine but not pancreastatin from rat stomach ECL cells.</span> (manuscript)</div>",

year = "2006",

language = "English",

isbn = "91-85481-34-3",

publisher = "Institute of Experimental Medical Sciences",

type = "Doctoral Thesis (compilation)",

school = "Department of Experimental Medical Science",

}

TY - THES

T1 - Physiological and pathophysiological regulation of ECL-cell activity

AU - Lundgren, Maria

N1 - Defence details Date: 2006-01-19 Time: 09:15 Place: GK lecture hall, BMC, Sölvegatan 19 External reviewer(s) Name: Sandvik, Arne K. Title: Professor Affiliation: Norvegian University of Science and Technology --- <div class="article_info">P Ericsson, P Norlén, M Bernsand, P Alm, P Höglund and R Håkanson. <span class="article_issue_date">2003</span>. <span class="article_title">ECL cell histamine mobilization studied by gastric submucosal microdialysis in awake rats: Methodological considerations.</span> <span class="journal_series_title">Pharmacol Toxicol</span>, <span class="journal_volume">vol 93</span> <span class="journal_pages">pp 57-65</span>.</div> <div class="article_info">T Konagaya, M Bernsand, P Norlén and R Håkanson. <span class="article_issue_date">2001</span>. <span class="article_title">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.</span> <span class="journal_series_title">Br J Pharmacol</span>, <span class="journal_volume">vol 133</span> <span class="journal_pages">pp 37-42</span>.</div> <div class="article_info">P Norlén, M Bernsand, T Konagaya and R Håkanson. <span class="article_issue_date">2001</span>. <span class="article_title">ECL-cell histamine mobilization in conscious rats: effects of locally applied regulatory peptides, candidate neurotransmitters and inflammatory mediators.</span> <span class="journal_series_title">Br J Pharmacol</span>, <span class="journal_volume">vol 134</span> <span class="journal_pages">pp 1767-1777</span>.</div> <div class="article_info">M Bernsand, R Håkanson and P Norlén. <span class="article_issue_date"></span>. <span class="article_title">Tachyphylaxis of the ECL-cell histamine response to PACAP: Depletion or desensitization?</span> (manuscript)</div> <div class="article_info">M Bernsand, P Ericsson, M Björkqvist, C-M Zhao, R Håkanson and P Norlén. <span class="article_issue_date">2003</span>. <span class="article_title">Submucosal microinfusion of endothelin and adrenaline mobilizes ECL-cell histamine in rat stomach, and causes mucosal damage: a microdialysis study.</span> <span class="journal_series_title">Br J Pharmacol</span>, <span class="journal_volume">vol 140</span> <span class="journal_pages">pp 707-717</span>.</div> <div class="article_info">M Kitano, M Bernsand, Y Kishimoto, P Norlén, R Håkanson, Y Haenuki, M Kudo and J Hasegava. <span class="article_issue_date">2005</span>. <span class="article_title">Ischemia of the rat stomach mobilizes ECL-histamine.</span> <span class="journal_series_title">Am J Physiol</span>, <span class="journal_volume">vol 288</span> <span class="journal_pages">pp G1084-G1090</span>.</div> <div class="article_info">M Bernsand, R Håkanson and P Norlén. <span class="article_issue_date"></span>. <span class="article_title">Ischemia mobilizes histamine but not pancreastatin from rat stomach ECL cells.</span> (manuscript)</div>

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

KW - pharmacy

KW - toxicology

KW - Pharmacological sciences

KW - pharmacognosy

KW - Gastroenterologi

KW - endothelin

KW - gastrin

KW - ischemia-reperfusion

KW - Physiology

KW - Fysiologi

KW - Gastro-enterology

KW - pancreastatin

KW - histamine

KW - microdialysis

KW - ECL-cell

KW - stomach

KW - Farmakologi

KW - farmakognosi

KW - farmaci

KW - toxikologi

M3 - Doctoral Thesis (compilation)

SN - 91-85481-34-3

PB - Institute of Experimental Medical Sciences

ER -

Physiological and pathophysiological regulation of ECL-cell activity

Abstract

Bibliographical note

Subject classification (UKÄ)

Free keywords

Fingerprint

Cite this