Modulation of ischemic-induced damage to cerebral adenylate cyclase in gerbils by calcium channel blockers.
It has been previously established that prolonged bilateral carotid occlusion followed by recirculation produces damage to the synaptic enzyme adenylate cyclase in the frontal cortex of the gerbil. Since calcium entrance into the brain may account in part for the deleterious consequences of stroke, the present study examined whether pretreatment with calcium channel blockers would modify the effects of 60 min of bilateral ischemia plus 40 min of reflow on various parameters of cortical adenylate cyclase activation. In this context activation of cerebral homogenates by norepinephrine with or without 5'-guanylyl imidodiphosphate was preserved by pretreatment of ischemic gerbils with verapamil but worsened by flunarizine. In contrast, in particulate fractions (treated with EGTA to reduce metallic ion levels) the damage to the Mn2+-sensitive catalytic site of adenylate cyclase was prevented only by flunarizine. Pretreatment with the two calcium channel blockers resulted in an elevated basal activity of the enzyme, thereby reducing the response in the homogenate preparation to forskolin. Gerbils pretreated with verapamil tended to have an increased ability for survival resulting from the ischemic episode. Under in vitro conditions the enzyme preparations were not markedly influenced by either drug.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D005444:Flunarizine / Q000494:pharmacology / Q000627:therapeutic use*; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D008345:Manganese / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use*
D002121:Calcium Channel Blockers; D008345:Manganese; D014700:Verapamil; D000262:Adenylyl Cyclases; D005444:Flunarizine