Rilmenidine elevates cytosolic free calcium concentration in suspended cerebral astrocytes.

M A Ozog, J X Wilson, S J Dixon, D F Cechetto

Index: J. Neurochem. 71 , 1429-1435, (1998)

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Abstract

Rilmenidine, a ligand for imidazoline and alpha2-adrenergic receptors, is neuroprotective following focal cerebral ischemia. We investigated the effects of rilmenidine on cytosolic free Ca2+ concentration ([Ca2+]i) in rat astrocytes. Rilmenidine caused concentration-dependent elevation of [Ca2+]i, consisting of a transient increase (1-100 microM rilmenidine) or a transient increase followed by sustained elevation above basal levels (1-10 mM rilmenidine). A similar elevation in [Ca2+]i was induced by the imidazoline ligand cirazoline. The transient response to rilmenidine was observed in Ca2+-free medium, indicating that rilmenidine evokes release of Ca2+ from intracellular stores. However, the sustained elevation of Ca2+ was completely dependent on extracellular Ca2+, consistent with rilmenidine activating Ca2+ influx. Pretreatment with thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-ATPase, abolished the response to rilmenidine, confirming the involvement of intracellular stores and suggesting that rilmenidine and thapsigargin activate a common Ca2+ influx pathway. The alpha2-adrenergic antagonist rauwolscine attenuated the increase in [Ca2+]i induced by clonidine (a selective alpha2 agonist), but not the response to rilmenidine. These results indicate that rilmenidine stimulates both Ca2+ release from intracellular stores and Ca2+ influx by a mechanism independent of alpha2-adrenergic receptors. In vivo, rilmenidine may enhance uptake of Ca2+ from the extracellular fluid by astrocytes, a process that may contribute to the neuroprotective effects of this agent.