In vitro evidence supporting two mechanisms of action for the anion transport inhibitor L-644,711 in cerebral ischaemia.
L-644,711 is a novel anion channel inhibitor which has previously been shown to decrease brain injury in two related rabbit models of cerebral ischaemia. We hypothesize two mechanisms of action of L-644,711 for its salutary effects on cerebral ischaemia: inhibition of neutrophil function and prevention of excitotoxin release from astrocytes. We present in vitro evidence supporting these two mechanisms of action. L-644,711 demonstrated a dose dependent inhibition of fMLP-induced neutrophil aggregation and superoxide anion release. In addition, L-644,711 demonstrated a dose dependent inhibition of glutamate release from swollen astrocytes in primary culture. We conclude that L-644,711 may prevent brain injury in cerebral ischaemia by inhibiting neutrophil function and preventing release of glutamate from swollen astrocytes.
Division of Neurosurgery, Vermont Center for Vascular Research, Burlington 05401.
M M
MM
Bednar
J J
JJ
Kohut
H K
HK
Kimelberg
J J
JJ
Gross
C E
CE
Gross
D000818:Animals; D000838:Anions / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy*; D002449:Cell Aggregation / Q000187:drug effects; D005449:Fluorenes / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism
D000838:Anions; D005449:Fluorenes; D005971:Glutamates; D013481:Superoxides; D018698:Glutamic Acid; C053396:L 644711