Adrenomedullin expression and function in the rat carotid body.
Adrenomedullin (AM) immunoreactivity has been found in granules of the glomus (type I) cells of the carotid bodies in rats. The identity of these cells was ascertained by colocalization of immunoreactivities for AM and tyrosine hydroxylase in their cytoplasm. Exposure of freshly isolated carotid bodies to synthetic AM resulted in a concentration- and time-dependent degranulation of glomus cells as measured by dopamine (DA) release. DA release reached a zenith 30 min after exposure to AM (94.2% over untreated controls). At this time-point, the response to AM was similar to the one elicited by 5 min of exposure to 100 mM K+. Nevertheless, injection of 1 micro l 60 nM AM/g body weight into the tail vein of the rats did not induce statistical differences in DA release from the carotid bodies. Exposure of the oxygen-sensitive cell line PC-12 to hypoxia elicited an increase in AM mRNA expression and peptide secretion into serum-free conditioned medium. Previous data have shown that elevation of AM expression under hypoxia is mediated through hypoxia-inducible factor-1, and that exposure of chromaffin cells to AM results in degranulation. All these data suggest that AM is an important autocrine regulator of carotid body function.
Martínez
A
A
Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 13N262, Bethesda, Maryland 20892, USA. martinez@mail.nih.gov
Saldise
L
L
Ramírez
M J
MJ
Belzunegui
S
S
Zudaire
E
E
Luquin
M R
MR
Cuttitta
F
F
D053607:Adrenomedullin; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002344:Carotid Body / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D003593:Cytoplasm / Q000737:chemistry; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D008297:Male; D018613:Microscopy, Confocal; D010455:Peptides / Q000032:analysis* / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D010455:Peptides; D012333:RNA, Messenger; D053607:Adrenomedullin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine