Synergistic regulation of cytosolic Ca2+ concentration in mouse astrocytes by NK1 tachykinin and adenosine agonists.
The effects on cytosolic Ca2+ concentration of 2-chloroadenosine and [L-Pro9]-substance P, a selective agonist of NK1 receptors, were investigated on astrocytes from embryonic mice in primary culture. Cells responded to [L-Pro9]-substance P with a transitory increase in cytosolic Ca2+ which was of shorter duration when external Ca2+ was removed. A transient response to 2-chloroadenosine alone occurred. When simultaneously applied, [L-Pro9]-substance P and 2-chloroadenosine evoked a prolonged elevation of cytosolic Ca2+ (up to 30 min). This phenomenon was dependent on the presence of extracellular Ca2+, but insensitive to dihydropyridines, La3+, and Co2+, excluding the implication of voltage-operated Ca2+ channels. Arachidonic acid also induced a sustained elevation of cytosolic Ca2+, but did not increase further the response evoked by [L-Pro9]-substance P and 2-chloroadenosine. The activation of protein kinase C by a diacylglycerol analogue mimicked the effect of [L-Pro9]-substance P in potentiating the 2-chloroadenosine-evoked response. Like 2-chloroadenosine, pinacidil, which hyperpolarizes the cells by opening K+ channels, prolonged the elevation of cytosolic Ca2+ concentration induced by [L-Pro9]-substance P. Conversely, depolarization with 50 mM KCl canceled the effects of either pinacidil or 2-chloroadenosine applied with [L-Pro9]-substance P. Pertussis toxin pretreatment suppressed all the effects induced by 2-chloroadenosine.
Delumeau
J C
JC
Chaire of Neuropharmacology INSERM U.114, Collège de France, Paris.
Petitet
F
F
Cordier
J
J
Glowinski
J
J
Prémont
J
J
D015762:2-Chloroadenosine / Q000494:pharmacology; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000241:Adenosine / Q000502:physiology*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D004357:Drug Synergism; D004789:Enzyme Activation; D051379:Mice; D009994:Osmolar Concentration; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D011983:Receptors, Purinergic / Q000502:physiology; D018039:Receptors, Tachykinin; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000502:physiology*
D017981:Receptors, Neurotransmitter; D011983:Receptors, Purinergic; D018039:Receptors, Tachykinin; D015320:Tachykinins; C067285:substance P, Pro(9)-; D015117:5,8,11,14-Eicosatetraynoic Acid; D015762:2-Chloroadenosine; D016718:Arachidonic Acid; D013373:Substance P; D011493:Protein Kinase C; D000241:Adenosine; D002118:Calcium