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Rilmenidine Elevates Cytosolic Free Calcium Concentration in Suspended Cerebral Astrocytes
Author(s) -
Ozog Mark A.,
Wilson John X.,
Dixon S. Jeffrey,
Cechetto David F.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71041429.x
Subject(s) - rilmenidine , thapsigargin , imidazoline receptor , chemistry , endocrinology , extracellular , agonist , medicine , pharmacology , biophysics , receptor , biology , biochemistry
Rilmenidine, a ligand for imidazoline and α 2 ‐adrenergic receptors, is neuroprotective following focal cerebral ischemia. We investigated the effects of rilmenidine on cytosolic free Ca 2+ concentration ([Ca 2+ ] i ) in rat astrocytes. Rilmenidine caused concentration‐dependent elevation of [Ca 2+ ] i , consisting of a transient increase (1–100 µ M rilmenidine) or a transient increase followed by sustained elevation above basal levels (1–10 m M rilmenidine). A similar elevation in [Ca 2+ ] i was induced by the imidazoline ligand cirazoline. The transient response to rilmenidine was observed in Ca 2+ ‐free medium, indicating that rilmenidine evokes release of Ca 2+ from intracellular stores. However, the sustained elevation of Ca 2+ was completely dependent on extracellular Ca 2+ , consistent with rilmenidine activating Ca 2+ influx.Pretreatment with thapsigargin, an inhibitor of the endoplasmic reticulum Ca 2+ ‐ATPase, abolished the response to rilmenidine, confirming the involvement of intracellular stores and suggesting that rilmenidine and thapsigargin activate a common Ca 2+ influx pathway. The α 2 ‐adrenergic antagonist rauwolscine attenuated the increase in [Ca 2+ ] i induced by clonidine (a selective α 2 agonist), but not the response to rilmenidine. These results indicate that rilmenidine stimulates both Ca 2+ release from intracellular stores and Ca 2+ influx by a mechanism independent of α 2 ‐adrenergic receptors. In vivo, rilmenidine may enhance uptake of Ca 2+ from the extracellular fluid by astrocytes, a process that may contribute to the neuroprotective effects of this agent.