Isradipine, a calcium channel blocker, attenuates the ischemia-induced release of dopamine but not glutamate in rats.

This study was designed to investigate the role of the L-type voltage sensitive calcium channel blocker, isradipine, in the ischemia-induced release of neurotransmitters. Male spontaneously hypertensive rats were subjected to cerebral ischemia for 60 min by bilateral carotid artery occlusion, and recirculated for 120 min. Isradipine (0.25 mg/kg n = 6) or vehicle (n = 6) was administered subcutaneously at 20 min before ischemia. In the striatum, cerebral blood flow was determined by the hydrogen clearance method and concentrations of extracellular dopamine and glutamate were measured by in vivo brain dialysis technique. Extracellular dopamine in the vehicle-treated group increased by 180-fold from the basal level, and glutamate by 24-fold during cerebral ischemia. Isradipine significantly attenuated the ischemic release of dopamine to 33-34% (P < 0.05) of the vehicle group, while it did not affect glutamate release. It is suggested that the release mechanism of dopamine and glutamate during cerebral ischemia may be different, especially in the dependence on the L-type calcium channels.