Role of ET-1 in hypoxia-induced mitosis of cultured rat carotid body chemoreceptors.

Abstract

The mammalian carotid body (CB) contains O2-chemoreceptors, i.e. glomus cells, which display increased mitoses and endothelin-1 (ET-1) expression during chronic hypoxia. To investigate whether endogenous ET-1 might mediate these mitogenic effects, we quantified bromodeoxyuridine (BrdU) uptake by tyrosine hydroxylase (TH)-positive glomus cells in rat CB cultures using double-label immunofluorescence. In normoxia (20% O2), 2-day exposure to ET-1 (10-1000 nM) caused a dose-dependent increase in BrdU uptake which peaked (approximately 55% of TH+ cells) at around 500 nM ET-1. In chronic hypoxia (5% O2) alone, BrdU uptake was stimulated (approximately 46% of TH+ cells) relative to normoxia (approximately 30%), but the effect was abolished in the presence of specific (BQ 123) or non-specific (PD 142893) ETA receptor antagonists (10(-5) M). Thus paracrine/autocrine release of ET-1 in the hypoxic carotid body may promote glomus cell mitosis via ET(A) receptors.

• Authors: M Paciga, C Vollmer, C Nurse
• Journal: Neuroreport (Neuroreport) Vol. 10 Issue 18 Pg. 3739-44 (Dec 16 1999) ISSN: 0959-4965 [Print] England
• PMID: 10716201 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelin-1
• Receptor, Endothelin A
• Receptors, Endothelin
• Bromodeoxyuridine

Topics

• Animals
• Bromodeoxyuridine (metabolism)
• Carotid Body (drug effects, pathology)
• Cell Survival (drug effects)
• Cells, Cultured
• Chemoreceptor Cells (drug effects, pathology)
• Chronic Disease
• Endothelin-1 (pharmacology, physiology)
• Hypoxia (metabolism, physiopathology)
• Mitosis
• Rats
• Receptor, Endothelin A
• Receptors, Endothelin (physiology)
• Reference Values