Increased activation of L-type voltage-dependent calcium channels is associated with glycine enhancement of N-methyl-D-aspartate-stimulated dopamine release in global cerebral ischemia/reperfusion.
We investigated the relationships among N-methyl-D-aspartate, glycine, L-type voltage-dependent calcium channels, and [3H]dopamine release in a canine model of global cerebral ischemia/reperfusion. The binding of [3H]PN200-110 ([3H]isradipine) to L-type voltage-dependent calcium channels, that open as a consequence of N-methyl-D-aspartate-induced changes in membrane potential, was approximately doubled in striatal membranes prepared from ischemic animals relative to controls, and remained significantly elevated at 30 min and 2 h of reperfusion. These changes coincided temporally with changes in the ability of the voltage-sensitive calcium channel blocker nitrendipine to inhibit glycine enhancement of N-methyl-D-aspartate-stimulated [3H]dopamine release in striatal slices prepared from the same animals. Compared with nonischemic controls, N-methyl-D-aspartate-stimulated [3H]dopamine release was increased in ischemic animals and remained increased throughout reperfusion up to at least 24 h. Glycine enhanced N-methyl-D-aspartate-stimulated release in all treatment groups. The enhancement of N-methyl-D-aspartate-stimulated dopamine release by glycine was reduced by the inclusion of nitrendipine in striatal slices from ischemic and 30-min reperfused animals. These data suggest that glycine may facilitate opening of the voltage-dependent calcium channels activated by N-methyl-D-aspartate and that this facilitation is blocked by the antagonist nitrendipine.
Werling
L L
LL
Department of Pharmacology, George Washington University Medical Center, Washington, D.C. 20037.
Hoehner
P J
PJ
Hurt
K J
KJ
Fox
L G
LG
Blanck
T J
TJ
Rosenthal
R E
RE
Fiskum
G
G
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D004285:Dogs; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005998:Glycine / Q000494:pharmacology*; D017275:Isradipine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology*; D009568:Nitrendipine / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium
D015220:Calcium Channels; D014316:Tritium; D016202:N-Methylaspartate; D009568:Nitrendipine; D005998:Glycine; D004298:Dopamine; D017275:Isradipine