Second messenger regulation of tyrosine hydroxylase gene expression in rat carotid body.
Previous studies [Czyzyk-Krzeska et al.: J Neurochem 1992;58:1538] demonstrated the relationship between low O2 breathing and tyrosine hydroxylase (TH) gene expression in chemosensory type I cells of the carotid body. In the present study, we have exposed carotid bodies in vitro to hypoxic superfusion media, and subsequently used the reverse transcriptase-polymerase chain reaction technique to measure relative changes in the TH transcript in an effort to elucidate the cellular mechanisms which regulate TH gene expression. Carotid bodies and superior cervical ganglia (SCG) were exposed for 3 h to superfusion media equilibrated with either 10% O2 or 100% O2 and then rapidly frozen on dry ice prior to extraction of total RNA. Hypoxia elevated TH mRNA in the carotid body 3.63 +/- 0.84-fold (mean +/- SEM), while in contrast, these parameters were unchanged in SCG similarly exposed to hypoxic media. Incubation of carotid bodies in zero Ca2+ superfusates greatly attenuated the increase in TH mRNA evoked by hypoxia (1.39 +/- 0.34-fold increase; p < 0.025 compared to normal Ca2+ group). Likewise, exposure to the guanylate cyclase activator, atriopeptin III (100 nM), attenuated the TH mRNA hypoxic response (p < 0.005), while activation of adenylate cyclase with forskolin (10 microM) tended to elevate the response to low O2. Our data suggest that hypoxia, independent of circulating hormones, induces TH gene expression in the carotid body, and that multiple factors, including [Ca2+] and cyclic nucleotides, may be important components of the signal transduction pathway.
Chen
J
J
Department of Physiology, University of Utah School of Medicine, Salt Lake City 84108, USA.
Dinger
B
B
Fidone
S J
SJ
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001483:Base Sequence; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002344:Carotid Body / Q000187:drug effects / Q000201:enzymology*; D015687:Cell Hypoxia; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D006162:Guanylate Cyclase / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009924:Organ Culture Techniques; D010100:Oxygen / Q000097:blood*; D010446:Peptide Fragments; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015290:Second Messenger Systems / Q000502:physiology*; D017783:Superior Cervical Ganglion / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics
D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D005576:Colforsin; C062525:atrial natriuretic factor prohormone (103-126); D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D010100:Oxygen; D002118:Calcium