Rilmenidine Elevates Cytosolic Free Calcium Concentration in Suspended Cerebral Astrocytes

Abstract

Rilmenidine, a ligand for imidazoline and a 2-adrenergic receptors, is neuroprotective following focal cerebral ischemia. We investigated the effects of rilmenidine on cytosolic free Ca 2concentration ([Ca2]) in rat astrocytes. Rilmenidine caused concentration-dependent elevation of [Ca2~], consisting of a transient increase (1-100~iMrilmenidine) or a transient increase followed by sustained elevation above basal levels (1-10 mM rilmenidine). A similar elevation in [Ca2~],was induced by the imidazoline ligand cirazoline. The transient response to rilmenidine was observed in Ca2-free medium, indicating that rilmenidine evokes release of Ca2f rom 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 a 2-adrenergic antagonist rauwolscine attenuated the increase in [Ca 2~]ĩnduced by clonidine (a selective a 2 agonist), but not the response to rilmenidine. These results indicate that rilmenidine stimulates both Ca 2~release from intracellular stores and Ca2~influx by a mechanism independent of a 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.

Rilmenidine improves hepatic steatosis through p38-dependent pathway to higher the expression of farnesoid X receptor

“…It has been indicated that rilmenidine has an ability to elevate cytosolic free calcium concentration in suspended cerebral astrocytes (Ozog et al 1998). Also, calcium ameliorates obesity induced by high-fat diet (Sun et al 2011).…”

Protection in Glutamate-Induced Neurotoxicity by Imidazoline Receptor Agonist Moxonidine

“…Rilmenidine elevates cytosolic free calcium concentration in suspended cerebral astrocytes. It was reported that rilmenidine stimulates both Ca 2+ release from intracellular stores and may enhance uptake of Ca 2+ from the extracellular fluid by astrocytes; the mean scores of rilmenidine neuroprotection may be related to its ability to induce astrocytic Ca 2+ influx (Chen et al, 2009;Ozog, Wilson, Dixon, & Cechetto, 1998). The stimulation of Ca 2+ uptake into astrocytes and reactive astrocytosis surrounding and providing tropic support to the injured neuron may contribute to the neuroprotection offered by moxonidine.…”

Neuroprotection by Alpha 2-Adrenergic Agonists in Cerebral Ischemia

“…Within the cerebral cortex, neuronal imidazoline receptors are absent [39], whereas cortical astrocytes express the imidazoline I 2 subtype on the outer mitochondrial membrane [80]. Ozog et al [65] concluded that rilmenidine in vivo may enhance uptake of calcium from extracellular fluid by astrocytes, a process that may contribute to the neuroprotecive effects of this agent. Rilmenidine stimulates both Ca 2+ release from intracellular stores and Ca 2+ influx by a mechanism independent of alpha 2-adrenergic receptors.…”

“…The same depolarizing and increased Ca ++ influx via voltage gated Ca ++ channels will also lead to release of other neurotransmitters. Recently, alpha 2-adrenergic agonists have been shown to improve the histomorphological and neurological outcome after cerebral ischemia when administered during and before ischemia, suggesting that epinephrine release could also contribute to post-ischemic damage [3,27,28,32,33,45,52,53,65,81]. Since the 1970s, alpha 2-adrenergic agonists have been applied successfully to treat patients with hypertension and to decrease afterload in congestive heart failure and aortic surgery [38].…”