Hypoxia increases the cyclic AMP content of the cat carotid body in vitro.
The cyclic AMP content of cat carotid bodies in vitro measured with a radioimmunoassay under control conditions (PO2: 230 torr) was 0.79 +/- 0.10 pmol/carotid body (n = 10). Lowering medium PO2 to 20 torr for 2 min significantly increased cyclic AMP content to 1.13 +/- 0.14 pmol/carotid body (n = 10). This increase was inhibited neither by propranolol (34 microM) nor by propranolol plus haloperidol (27 microM). Inhibition of the cyclic nucleotide phosphodiesterase with 1-methyl-3-isobutylxanthine (0.8 mM) provoked a fast and large increase in cyclic AMP during both control and hypoxic conditions. The cyclic AMP increase induced by hypoxia was still observed when extracellular Ca2+ was absent. Inhibition of the adenylate cyclase by N-(cis-2-phenylcyclopentyl)azacyclotridecan-2-imine hydrochloride (MDL 12330A; 20-1,000 microM) under zero-Ca2+ conditions irreversibly inhibited the cyclic AMP increase produced by hypoxia. Similarly, inhibition of the Ca2(+)-calmodulin complex by trifluoperazine (0.2 mM) or calmidazolium (R 24571; 50-200 microM) prevented the cyclic AMP response. These results suggest that cyclic AMP may be involved in the PO2-sensing mechanism of the carotid body. Hypoxia appears to activate adenylate cyclase directly and independent of any hormone-receptor interactions.
Delpiano
M A
MA
Max-Planck-Institut für Systemphysiologie, Dortmund, F.R.G.
Acker
H
H
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002344:Carotid Body / Q000378:metabolism*; D002415:Cats; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009420:Nervous System / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012016:Reference Values
D000067956:Adenylyl Cyclase Inhibitors; D010726:Phosphodiesterase Inhibitors; D011433:Propranolol; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D006220:Haloperidol; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine