Hypoxia inhibits the synthesis of phosphoinositides in the rabbit carotid body.
Hypoxic transduction in the carotid body (CB) is regulated by several systems of second messengers, but the role of the phospholipase C system has not been studied. The aim of the present study was to characterize the turnover rate of inositol phosphates (InsPs) and phosphoinositides (PIs) and their modifications by hypoxia in the rabbit CB in vitro. In CBs, in which the PIs had been labelled previously with 3H-myo-inositol, hypoxia in the presence of LiCl did not modify the accumulation of 3H-InsPs, whilst exposure to hypoxia during the loading period in the presence of LiCl reduced the accumulation of 3H-InsPs by more than 50%. Endogenous levels of inositol 1,4,5-trisphosphate were unaltered by hypoxia. Synthesis of 3H-PIs from 3H-myo-inositol was markedly inhibited by hypoxia in the CB, but not in the rat superior cervical ganglion used as control tissue. Levels of 3H-phosphatidylinositol (3H-PtdIns), 3H-phosphatidylinositol 4-monophosphate and 3H-phosphatidylinositol 4,5-bisphosphate were similarly decreased, indicating that inhibition occurs at a step prior to PtdIns synthesis. It is concluded that the phospholipase C system of second messengers does not play a significant role in the short-term regulation of hypoxic transduction cascade. It can be speculated that the decrease in PI availability produced by hypoxia might be involved in the functional changes observed in the CB on chronic hypoxic exposure.
Rigual
R
R
Departamento de Bioquímica y Biologia Molecular y Fisiología, Instituto de Biología y Génetica Molecular (IBGM) CSIC, Facultad de Medicina, Universidad de Valladolid, E-47005 Valladolid, Spain. rrigual@ibgm.uva.es
Cachero
M T
MT
Rocher
A
A
González
C
C
D000818:Animals; D002344:Carotid Body / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000096:biosynthesis*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems; D014316:Tritium; D010738:Type C Phospholipases / Q000378:metabolism
D010716:Phosphatidylinositols; D014316:Tritium; D007294:Inositol; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D018021:Lithium Chloride