RGD Reference Report - Endothelin-1 induces organ-specific histamine liberation and neutrophil granulocyte accumulation in the rat. - Rat Genome Database

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Endothelin-1 induces organ-specific histamine liberation and neutrophil granulocyte accumulation in the rat.

Authors: Kaszaki, J  Czobel, M  Szalay, L  Nagy, S  Boros, M 
Citation: Kaszaki J, etal., Inflamm Res. 2008 Aug;57(8):396-402.
RGD ID: 4892576
Pubmed: PMID:18787779   (View Abstract at PubMed)
DOI: DOI:10.1007/s00011-007-7224-x   (Journal Full-text)

OBJECTIVE AND DESIGN: Enhanced production of endothelin-1 (ET-1) and the activation of mast cells (MCs) have been implicated in granulocyte sequestration. We compared local consequences of transient increases in circulating ET-1 in three separate circulatory beds in pentobarbital-anesthetized Wistar rats. MATERIALS AND METHODS: We determined whether pretreatment with ET-A receptor antagonist ETR-P1/fl peptide and MC stabilizer sodium cromoglycate would influence histamine- and granulocyte responses induced by 1 nmol/kg ET-1 iv. Plasma and tissue histamine contents were monitored, myeloperoxidase (MPO) level was determined from heart, lung and intestinal biopsies. RESULTS: The ET-1 infusion caused significant plasma histamine elevations, enhanced MPO activity in all organs, decreased tissue histamine content in the lung and small bowel by approx. 50% , while the histamine content of heart did not change. ETR-P1/fl significantly decreased ET-1-induced intestinal and heart MPO changes, and inhibited histamine depletion in the small intestine but not in lung and heart tissues. Sodium cromoglycate inhibited the ET-1-induced neutrophil accumulation in the heart and intestine and did not influence MPO activity in the lung. CONCLUSION: ET-1 release participates in the process of histamine liberation and subsequent secondary granulocyte accumulation through tissue-specific activation of ET-A receptors. ET-1-induced direct effects are predominating in pulmonary neutrophil activation, while MC-associated secondary changes play important roles in intestinal granulocyte recruitment.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Edn1  (endothelin 1)
Ednra  (endothelin receptor type A)


Additional Information