Excessive release of [3H] noradrenaline by veratridine and ischemia in spinal cord.
In this study, the properties of ischemic condition-induced and veratridine-evoked [3H]noradrenaline ([3H]NA) release from rat spinal cord slices were compared. It was expected that ischemia mimicked by oxygen and glucose deprivation results in the impairment of Na+/K+ -ATPase with a consequent elevation of the intracellular Na+ -level which reverses the NA carrier and promotes excessive NA release, and veratridine, by the activation of Na+ channels, releases NA both carrier-mediated and Ca2+ -dependent, i.e. vesicular manner. In our experiments, veratridine (1-100 microM) dose-dependently increased the resting [3H]NA release, and its effect was only partially blocked by low temperature or the lack of external calcium, whereas the sodium channel inhibitor tetrodotoxin (TTX, 1 microM) completely prevented it, indicating that veratridine induces NA release via axonal depolarization and reversing the transporters by eliciting Na+ -influx. In contrast to TTX, the local anesthetic lidocaine (100 microM) only partially blocked the veratridine-induced [3H]NA release due to its inhibitory action on K+ channels. The ischemia-induced [3H]NA release was abolished at 12 degrees C, a temperature known to block only the transporter-mediated release of transmitters. However, lidocaine was also partially effective to reverse the action of ischemia on the NA release, indicating that lidocaine is not a useful compound in the treatment of spinal cord-injured patients against the excessive excytotoxic NA release.
Sumiya
Y
Y
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, P.O.Box 67, H-1450, Budapest, Hungary.
Torigoe
K
K
Gerevich
Z
Z
Köfalvi
A
A
Vizi
E S
ES
D000818:Animals; D015687:Cell Hypoxia; D003080:Cold Temperature; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D014701:Veratridine / Q000494:pharmacology*
D014316:Tritium; D013779:Tetrodotoxin; D014701:Veratridine; D005947:Glucose; D009638:Norepinephrine