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

Eur J Pharmacol. 1995 Mar 15;289(1):113-23. doi: 10.1016/0922-4106(95)90176-0.

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) occurring 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 occurring 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Amino Acid Oxidoreductases / metabolism
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Calcium / metabolism*
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / metabolism
  • Cyclic GMP / pharmacology
  • Homeostasis / physiology
  • Muscarinic Agonists
  • NG-Nitroarginine Methyl Ester
  • Neurons / metabolism*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase
  • Nitroprusside / pharmacology
  • PC12 Cells
  • Rats
  • Receptors, Muscarinic / physiology*
  • Signal Transduction / physiology

Substances

  • Muscarinic Agonists
  • Receptors, Muscarinic
  • Nitroprusside
  • 8-bromocyclic GMP
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Cyclic GMP
  • Calcium
  • NG-Nitroarginine Methyl Ester