Protein kinase C modulates ischemia-induced amino acids release in the striatum of hypertensive rats.
The role of protein kinase C (PKC) in mediating the ischemia-induced release of amino acids in the striatum was studied using an in vivo brain dialysis technique in the striatum of spontaneously hypertensive rats (SHRs). Using HPLC combined with fluorescence detection methods, we investigated the concentrations of amino acids in the dialysates produced by 20 min of transient forebrain ischemia. We studied the effects of an inhibitor of PKC, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) and another isoquinoline analog (HA1004) with less inhibitory effect on the C kinase in ischemia-induced amino acids release. Bilateral carotid artery occlusion caused a marked reduction in the striatal blood flow by 91 +/- 6%. The extent of the cerebral blood flow (CBF) reduction were essentially the same among H7-, HA1004-, and the vehicle-treated groups. Forebrain ischemia produced a marked increase in glutamate (21-fold of the basal concentration), aspartate (19-fold) and taurine (16-fold). Pretreatment with H7 markedly attenuated the ischemia-in-duced release of these three amino acids to 3, 3 and 4-fold of the basal values, respectively. Increase of gamma-aminobutyric acid (GABA) was also attenuated by H7 (vehicle; 2.46 +/- 1.26 microM, H7; 0.62 +/- 0.75 mM). HA1004 did not affect the release of glutamate, aspartate or GABA during ischemia. The ischemia-induced release of taurine was significantly inhibited by HA1004 but the effect was much smaller than that of H7. These results thus indicate that PKC plays a major role in the ischemia-induced release of amino acids in the striatum of SHR.
Nakane
H
H
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan. hiroshi@uiowa.campus.mci.net
Yao
H
H
Ibayashi
S
S
Kitazono
T
T
Ooboshi
H
H
Uchimura
H
H
Fujishima
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D013449:Sulfonamides
D000596:Amino Acids; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D013449:Sulfonamides; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C