Physiological and pathophysiological regulation of ECL-cell activity
Författare
Summary, in English
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.
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.
Publiceringsår
2006
Språk
Engelska
Dokumenttyp
Doktorsavhandling
Förlag
Institute of Experimental Medical Sciences
Ämne
- Basic Medicine
Nyckelord
- pharmacy
- toxicology
- Pharmacological sciences
- pharmacognosy
- Gastroenterologi
- endothelin
- gastrin
- ischemia-reperfusion
- Physiology
- Fysiologi
- Gastro-enterology
- pancreastatin
- histamine
- microdialysis
- ECL-cell
- stomach
- Farmakologi
- farmakognosi
- farmaci
- toxikologi
Status
Published
Handledare
- Per Norlén
- Rolf Håkanson
ISBN/ISSN/Övrigt
- ISBN: 91-85481-34-3
Försvarsdatum
19 januari 2006
Försvarstid
09:15
Försvarsplats
GK lecture hall, BMC, Sölvegatan 19
Opponent
- Arne K. Sandvik (Professor)