Cyclic GMP inhibition of stimulated phosphoinositide hydrolysis in neuronal cultures.
We used a radioreceptor binding assay to analyse the effect of dibutyryl cyclic GMP (dbcGMP) and the nitric oxide (NO) donor sodium nitroprusside (SNP) on inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) mass accumulation in response to the muscarinic receptor agonist carbachol and K(+)-induced depolarization in neuronal primary cultures. In forebrain neurones carbachol induced a transient rise in Ins(1,4,5)P3 with a maximal increase of about 2.5-fold at 5 s. At this time 30 mM K+ induced a somewhat lower stimulation. Both carbachol and high K+ stimulations were significantly inhibited by dbcGMP and by SNP. The effect of SNP was blocked by haemoglobin. dbcGMP inhibition of the carbachol effect was also observed in cerebellar granule cell cultures. These results show for the first time that the NO/cGMP generating system can modulate phosphoinositide turnover in CNS neurones in a manner similar to that previously reported to occur in peripheral neurones and non-neuronal tissues.
Oliva
A M
AM
Instituto de Biología Fundamental V. Villar Palasí, Universidad Autónoma de Barcelona, Bellaterra, Spain.
García
A
A
D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000494:pharmacology*; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D010716:Phosphatidylinositols; D009599:Nitroprusside; D015544:Inositol 1,4,5-Trisphosphate; D006152:Cyclic GMP