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

Lundgren, Maria LU ; Håkanson, Rolf LU and Norlén, Per LU (2007) In British Journal of Pharmacology 152(2). p.240-248
Abstract
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 mu l(-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... (More)
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 mu l(-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 mu l(-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 mu l(-1)) abolished the response to a subsequent near-maximal PACAP challenge ( 0.3 nmol mu l(-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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ECL cells, histamine, pancreastatin, histidine decarboxylase, microdialysis, gastrin, rat stomach, somatostatin, PACAP
in
British Journal of Pharmacology
volume
152
issue
2
pages
240 - 248
publisher
The British Pharmacological Society
external identifiers
  • wos:000249324800009
  • scopus:34948896419
ISSN
1476-5381
DOI
10.1038/sj.bjp.0707385
language
English
LU publication?
yes
id
8974fd6d-5b27-4e1f-accb-f0d2da74aa9f (old id 688368)
date added to LUP
2007-12-05 15:15:08
date last changed
2017-01-01 06:38:58
@article{8974fd6d-5b27-4e1f-accb-f0d2da74aa9f,
  abstract     = {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 mu l(-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 mu l(-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 mu l(-1)) abolished the response to a subsequent near-maximal PACAP challenge ( 0.3 nmol mu l(-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.},
  author       = {Lundgren, Maria and Håkanson, Rolf and Norlén, Per},
  issn         = {1476-5381},
  keyword      = {ECL cells,histamine,pancreastatin,histidine decarboxylase,microdialysis,gastrin,rat stomach,somatostatin,PACAP},
  language     = {eng},
  number       = {2},
  pages        = {240--248},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Tachyphylaxis of the ECL-cell response to PACAP: receptor desensitization and/or depletion of secretory products},
  url          = {http://dx.doi.org/10.1038/sj.bjp.0707385},
  volume       = {152},
  year         = {2007},
}