Role of ET-1 in hypoxia-induced mitosis of cultured rat carotid body chemoreceptors.
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.
Paciga
M
M
Department of Biology, McMaster University, Hamilton, Ontario, Canada.
Vollmer
C
C
Nurse
C
C
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002344:Carotid Body / Q000187:drug effects / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000473:pathology*; D002908:Chronic Disease; D019332:Endothelin-1 / Q000494:pharmacology / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008938:Mitosis; D051381:Rats; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology; D012016:Reference Values
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D001973:Bromodeoxyuridine