Novel kainate derivatives: potent depolarizing actions on spinal motoneurones and dorsal root fibres in newborn rats.
1. Neuropharmacological actions of several kainate derivatives (kainoids) were examined for electrophysiological effects in the isolated spinal cord and the dorsal root fibre of the newborn rat. 2. Some kainoids caused depolarization of the motoneurone much more effectively than kainic acid or domoic acid and others were weaker. The rank order of the depolarizing activities of the kainoids tested here is as follows: 4-(2-methoxyphenyl)-2-carboxy-3-pyrrolidineacetic acid (MFPA) greater than acromelic acid A greater than domoic acid greater than or equal to 4-(2-hydroxyphenyl)-2-carboxy-3-pyrrolidineacetic acid (HFPA) greater than or equal to acromelic acid B greater than kainic acid. 3. In the isolated dorsal root fibre, domoic acid caused the most significant depolarization. There were distinct differences with regard to the rank order of the depolarizing activity between the motoneurone and the dorsal root fibre. The rank order in the dorsal root fibre is domoic acid greater than acromelic acid B greater than 5-bromowillardiine greater than or equal to MFPA greater than acromelic acid A greater than HFPA greater than kainic acid. 4. Significant desensitization of kainate receptors was observed in the isolated dorsal root fibre during prolonged application of L-glutamate, kainate and its derivatives. Cross desensitization was also observed among these excitatory amino acids. Receptors desensitized by kainate did not respond to MFPA, HFPA and acromelic acids, suggesting that these kainate derivatives activated common kainate receptors in the dorsal root fibre.(ABSTRACT TRUNCATED AT 250 WORDS)
Ishida
M
M
Tokyo Metropolitan Institute of Medical Science, Japan.
Shinozaki
H
H
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D000831:Animals, Newborn; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects; D013329:Structure-Activity Relationship
D009467:Neuromuscular Depolarizing Agents; D010879:Piperazines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C074250:4-(2-methoxyphenyl)-2-carboxy-3-pyrrolidineacetic acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C012301:domoic acid; C051743:acromelic acid A; D007608:Kainic Acid