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Tachyphylaxis of the ECL-cell response to PACAP: receptor desensitization and/or depletion of secretory products.

Authors: Bernsand, M  Hakanson, R  Norlen, P 
Citation: Bernsand M, etal., Br J Pharmacol. 2007 Sep;152(2):240-8. Epub 2007 Jul 30.
Pubmed: (View Article at PubMed) PMID:17660849
DOI: Full-text: DOI:10.1038/sj.bjp.0707385

BACKGROUND AND PURPOSE: Rat stomach ECL cells secrete histamine and pancreastatin in response to gastrin and pituitary adenylate cyclase-activating peptide-27 (PACAP). This study applies microdialysis to explore how ECL cells in situ respond to PACAP and gastrin. EXPERIMENTAL APPROACH: Both peptides were administered by microinfusion into the gastric submucosa. The microdialysate was analysed for histamine and pancreastatin (ECL-cell markers) and for somatostatin (D-cell marker). KEY RESULTS: Microinfusion of PACAP (0.01-0.3 nmol microl(-1)) raised microdialysate histamine and pancreastatin dose-dependently. The response was powerful but short-lived. The response to gastrin was sustained at all doses tested. It is unlikely that the transient nature of the histamine response to PACAP reflects inadequate histamine synthesis, since the pancreastatin response to PACAP was short-lived too, and both gastrin and PACAP activated ECL-cell histidine decarboxylase. Unlike gastrin, PACAP mobilized somatostatin. Co-infusion of somatostatin abolished the histamine-mobilizing effect of PACAP. However, pretreatment with the somatostatin receptor type-2 antagonist (PRL-2903) did not prolong the histamine response to PACAP, suggesting that mobilization of somatostatin does not explain the transient nature of the response. Repeated administration of 0.1 nmol microl(-1) of PACAP (1 h infusions, 1 h intervals) failed to induce a second histamine response. Pretreatment with a low dose of PACAP (0.03 nmol microl(-1)) abolished the response to a subsequent near-maximal PACAP challenge (0.3 nmol microl(-1)). CONCLUSION: The transient nature of the histamine response to PACAP reflects desensitization of the PACAP receptor and/or exhaustion of a specific storage compartment that responds to PACAP but not to gastrin.

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CRRD Object Information
CRRD ID: 2325283
Created: 2010-05-28
Species: All species
Last Modified: 2010-05-28
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.