Extracellular adenosine 5′-triphosphate-evoked norepinephrine secretion not relating to voltage-gated Ca channels in pheochromocytoma PC12 cells

doi:10.1016/0304-3940(89)90179-1

Neuroscience Letters

Volume 106, Issue 3, 4 December 1989, Pages 294-299

https://doi.org/10.1016/0304-3940(89)90179-1 Get rights and content

Abstract

Characteristics of extracellular ATP-stimulated norepinephrine (NE) secretion were investigated by the batch method in relation to membrane current measured with the whole cell voltage-clamp technique. Extracellular ATP stimulated [³H]NE secretion from PC12 cells in a concentration range from 10 μM to 1 mM. The maximal effect of ATP was about 5 times larger than that of nicotine. ATP-stimulated secretion was extracellular Ca-dependent, but it was not inhibited by the Ca-channel blockers, cadmium (300 μM) or nicardipine (10 μM). Extracellular ATP activated an inward current in PC12 cells and the peak amplitude of the current was about 5 times larger than that activated by nicotine. These findings suggest that extracellular ATP activates receptor-operated channels and causes NE secretion.

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The effects of purinoceptor subtypes on hippocampal extracellular serotonin levels were determined by using in vivo microdialysis. Perfusion with adenosine-5′-triphosphate (ATP) for 20 min produced concentration-dependent changes in hippocampal extracellular serotonin levels, which consisted of an initial rise phase, with levels increasing to 309% of control with 100 μM ATP, followed by a later rebound reduction phase, with levels decreasing to 6% of control. The P2X_1-7 active P2 purinoceptor agonist, 2-methylthioATP (2-MeSATP: 100 μM) increased the extracellular serotonin level drastically (638%), while the P2X_1,3 active P2 purinoceptor agonist, α,β-methylene-l-ATP (α,β-meATP: 100 μM) produced a small increase (132%) in the serotonin level. The P2X_1,2,3,5,7 active P2 purinoceptor antagonist, suramin (100 μM), reduced the basal serotonin level (86%) and the ATP-evoked initial rise phase (from 309 to 254%) without affecting the late reduction phase. The adenosine A₁ receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT: 50 μM) potentiated the rising phase (167%) and abolished the subsequent ATP-evoked reduction phase. Perfusion with CPT and an adenosine A₂ receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX: 10 μM), reduced the ATP-evoked initial rise (to 181%) and abolished the late reduction phases of serotonin release. These results indicate that ATP-evoked hippocampal serotonin release is composed of an initial rise phase and a later reduction phase. The ATP-evoked initial rise phase might be produced by an activation of P2X purinoceptor function, whereas the late reduction phase was modulated by the activation of adenosine A₁ receptor function by adenosine, metabolized from ATP in the synaptic cleft.
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1999, Progress in Brain Research
This chapter discusses the implications of ATP receptors in the function of the hippocampus. The chapter presents the information that ATP inhibits presynaptically the release of glutamate, an excitatory neurotransmitter from the hippocampus. Meanwhile, it has been reported that ATP stimulates the release of glycine, an inhibitory neurotransmitter from interneurons of dorsal horn. In hippocampus, ATP may stimulate the release of GABA from some interneurons. The inhibition of glutamate release and the stimulation of GABA and glycine release have the same effect as a negative feedback loop—that is, turning-down the activity of neurons stimulated by glutamate. ATP also activates microglia to release plasminogen, a type of neurotrophic factor, which promotes the development of mesencephalic dopaminergic neurons and enhances neurite outgrowth from explants of neocortical tissue. ATP may stimulate the reconstruction of synaptic networks through activating microglia. The chapter discusses several reports that show the trophic action of ATP itself in central nervous system (CNS). Thus, ATP may have a role in the protection of the function of neurons in hippocampus from over-stimulation by glutamate.
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This chapter investigates the effects of ATP and related nucleotides on PC12 cells. In PC12 cells, ATP is a powerful stimulator of catecholamine release probably through an increase in the intracellular levels of Ca²⁺. The ATP stimulated increase in Ca²⁺ appears to be because of several actions possibly mediated through different receptors. The culture conditions of PC12 cells differ among laboratories and PC12 cells have been shown to be able to change their phenotype, not only when cultured with different differentiating factors such as neurotrophins, but also spontaneously. The chapter investigates the possible sources of variability, which can be schematically subdivided into three levels: first, genetic differences within the same cell clone because of spontaneous mutations of some cells leading to the coexistence of different cell types; second, phenotypic differences because of differentiation induced by specific substances such as NGF; third, differences that can be revealed even in the same clone in the same phenotypic phase. The chapter presents the PC12 clones, isolated based on neomycin resistance, which show a relatively stable phenotype and have been employed for studies of calcium movements.
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The possible involvement of adenosine 5′–triphosphate (ATP) receptors in the function of the hippocampus is reviewed. The involvement of these receptors in the hippocampus is suggested by data that ATP is released from hippocampal slices [1], and that it also induces fast synaptic currents in cultured hippocampal neurons [2] and long–lasting enhancement of the population spikes [3–5]. In addition, ATP is released by glutamate–stimulation which leads to an increase in intracellular Ca²⁺in hippocampal cells [6], ATP also inhibits the glutamate release in cultured hippocampal neurons [7], and it has been shown that several mRNAs for certain types of P_2X–purinoceptors are present in this area [8]. It is therefore likely that ATP may play a role in the modulation of synaptic efficiency in the hippocampus. Microglia cells are activated by the stimulation of ATP and releases plasminogen but not nitric oxide (NO). It has been reported that plasminogen promotes the development of mesencephalic dopaminergic neurons and enhances neurite outgrowth from explants of neocortical tissue [9, 10]. The possibility that ATP protects brain function from over stimulation is discussed.

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Extracellular adenosine 5′-triphosphate-evoked norepinephrine secretion not relating to voltage-gated Ca channels in pheochromocytoma PC12 cells

Abstract

Biochem. Pharmacol.

Brain Res.

Brain Res.

J. Biol. Chem.

J. Biol. Chem.

A novel receptor-operated Ca2+-permeable channel activated by ATP in smooth muscle

Nature (Lond.)

Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by nonadrenergic inhibitory nerves in the gut

Br. J. Pharmacol.

Neural nomenclature

Nature (Lond.)

A dual function for adenosine 5′-triphosphate in the regulation of vascular tone; excitatory cotransmitter with noradrenaline from perivascular nerves and locally released inhibitory intravascular agent

Circ. Res.

Inhibition of catecholamine secretion from bovine chromaffin cells by adenine nucleotides and adenosine

J. Neurochem.

A novel receptor-operated Ca²⁺-permeable channel activated by ATP in smooth muscle