Preventive action of quisqualic acid against grayanotoxin-induced suppression of locomotor activity in mice.
Grayanotoxin-III (GTX-III) is a constituent in leaves of Pieris japonica D. Don which exhibits, in vitro, the ability to open voltage-sensitive sodium channels in various excitable tissues. Effects of systemic administration of GTX-III were studied in vivo using Std-ddy mice. Salivation, vomiting and paralysis of the hind paws invariably occurred in mice injected intraperitoneally with 0.1 or 0.25 mg/kg of GTX-III. The writhing response to an intraperitoneal injection of acetic acid was considerably diminished by pretreatment of animals with the toxin. The grayanoid also caused a profound attenuation of the response to caudal compression, while inducing no significant alteration of that to thermal injury. Pretreatment with GTX-III resulted in a significant decrement of the time required for loss of the righting reflex induced by pentobarbital, with a concomitant delay in recovery. Mice injected with the toxin exhibited a significant and restorable suppression of coordination, and a long-lasting suppression of spontaneous locomotor activity in both horizontal and vertical directions. Neither tetrodotoxin (1-5 micrograms/kg, i.p.) nor Ro15-1788 (1-5 mg/kg, i.p.) prevented the GTX-III-induced suppression of locomotion. Atropine (5-10 mg/kg, i.p.) failed to antagonize the GTX-III-induced suppression but protected against salivation induced by the toxin without affecting other symptoms. Intracerebroventricular injection of quisqualic acid (0.5 microgram), one of the agonists for central glutamate receptors, but not that of tetrodotoxin (5 ng) prevented the GTX-III-induced suppression of horizontal movement. These results suggest that GTX-III may elicit its depressant action on horizontal locomotion possibly through interacting with central glutamatergic neurons rather than activating voltage-sensitive sodium channels in the brain. Possible involvement of muscarinic cholinergic neurons in the GTX-III-induced salivation is also suggested.
Ohgaki
T
T
Department of Pharmacology, Setsunan University, Osaka, Japan.
Uchida
S
S
Meguri
H
H
Ogita
K
K
Yoneda
Y
Y
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004224:Diterpenes; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology*; D016318:Quisqualic Acid; D014118:Toxins, Biological
D000700:Analgesics; D004224:Diterpenes; D006993:Hypnotics and Sedatives; D009467:Neuromuscular Depolarizing Agents; D010069:Oxadiazoles; D014118:Toxins, Biological; D016318:Quisqualic Acid; C020751:grayanotoxin III