Nitric oxide modulates agonist-evoked Ca2+ release and influx responses in PC12-64 cells

Emilio Clementi, Immacolata Vecchio, Maria T. Corasaniti, Giuseppe Nisticó

Research output: Contribution to journalArticle

Abstract

Nitric oxide (NO) is a signalling molecule involved in events crucial to neuronal cell function such as neurotransmitter release gene transcription, and neurotoxicity. In these, as well as in many other neuronal processes, a key role may be played by the increases of the intracellular Ca2+ concentration ([Ca2+]i) occuring in response to activation of plasma membrane receptors coupled to phosphatidylinositol 4,5-bisphosphate hydrolysis. Such a [Ca2+]i increases are sustained by release of the cation from intracellular stores and stimulation of influx through specific Ca2+ channels. We have investigated the role of NO in modulating the two above Ca2+ processes occuring subsequently to muscarinic receptor activation in a selected clone (PC12-64) of PC12 cells, a neurosecretory/neuronal cell model. Analysis of [Ca2+]i variations in fura-2-loaded cells, exposed to different NO synthase inhibitors or NO donors, showed that Ca2+ release from intracellular stores was moderately inhibited and stimulated by these two groups of drugs, respectively, while Ca2+ influx through the channels directly coupled to muscarinic receptors was found to be insensitive to NO action. In contrast, Ca2+ influx activated by muscarinic receptor-induced store depletion (investigated also by Mn2+ quenching of the fura-2 signal) was increased by NO generation and inhibited by NO synthase blockade. Incubation of the cells with 8-bromo cGMP did not mimick the action of NO, suggesting that the effect of the messenger on Ca2+ influx is exerted through a signalling pathway different from cGMP generation.

Original languageEnglish
Pages (from-to)113-123
Number of pages11
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume289
Issue number1
DOIs
Publication statusPublished - Mar 15 1995

Keywords

  • Ca homeostasis
  • cGMP
  • Nitric oxide (NO)
  • Nitric oxide synthase
  • PC12 cell

ASJC Scopus subject areas

  • Pharmacology

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