Guanine nucleotide- and muscarinic agonist-dependent phosphoinositide metabolism in synaptoneurosomes from cerebral cortex of immature rats

Stefano M. Candura, Anna F. Castoldi, Luigi Manzo, Lucio G. Costa

Research output: Contribution to journalArticlepeer-review

Abstract

Guanine nucleotide-, neurotransmitter-, and fluoride-stimulated accumulation of [3H]inositol phosphates ([3H]InsPs) was measured in [3H]inositol-labeled synaptoneurosomes from cerebral cortex of immature (7-day-old) and adult rats, in order to clarify the role of GTP-binding proteins (G-proteins) in modulating phosphoinositide (PtdIns) metabolism during brain development. GTP(S) [Guanosine 5′-O-(3-thio)triphosphate] time- and concentration-dependently stimulated PtdIns hydrolysis. Its effect was potentiated by full (carbachol, metacholine) and partial (oxotremorine) cholinergic agonists through activation of muscarinic receptors. The presence of deoxycholate was required to demonstrate agonist protentiation of the guanine nucleotide effect. The response to GTP(S) was higher in adult than in immature rats, while the effect of cholinergic agonists was similar at the two ages examined. At both ages, histamine potentiated the effect of GTP(S), while norepinephrine was ineffective. At both ages, guanosine 5′-O-(2-thio)diphosphate [GDP(S)] and pertussis toxin significantly decreased GTP(S)-induced [3H]InsPs formation. The phorbol ester phorbol 12-myristate 13-acetate (PMA), on the other hand, did not inhibit the guanine nucleotide response in synaptoneurosomes from immature rats. NaF mimicked the action of GTP(S) in stimulating PtdIns hydrolysis. Its effect was not affected by carbachol and was highly synergistic with that of AlCl3, according to the concept that fluoroaluminate (AlF4-) is the active stimulatory species. No quantitative differences were found in the response to these salts between immature and adult animals. These results provide evidence that, in both the immature and adult rat brain, neuroreceptor activation is coupled to PtdIns hydrolysis through modulatory G-proteins.

Original languageEnglish
Pages (from-to)1133-1141
Number of pages9
JournalNeurochemical Research
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 1992

Keywords

  • G-proteins
  • immature rat
  • muscarinic receptor
  • phosphoinositide metabolism

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry

Fingerprint Dive into the research topics of 'Guanine nucleotide- and muscarinic agonist-dependent phosphoinositide metabolism in synaptoneurosomes from cerebral cortex of immature rats'. Together they form a unique fingerprint.

Cite this