Synergistic Regulation of Cytosolic Ca2+ Concentration in Mouse Astrocytes by NK1 Tachykinin and Adenosine Agonists

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Abstract
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 dihy‐dropyridines, 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 hyper‐polarizes the cells by opening K+ channels, prolonged the elevation of cytosolic Ca2+ concentration induced by [L‐Pro9]‐substance P. Conversely, depolarization with 50 mM KC1 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.