Domoic and quisqualic acids as potent amino acid excitants of frog and rat spinal neurones

Abstract

THE finding that kainic acid (Fig. 1a) is a potent glutamate-like excitant of rat cerebral¹ and cat spinal² neurones has led us to test domoic acid (Fig. 1b), which is structurally related to kainic acid and wnich also occurs in certain marine algae and has similar anthelmintic properties^3,4. We have also compared the actions of these two compounds with those of α-allo-kainic acid (Fig. 1c), a stereo-isomer of kainic acid and a weaker excitant of rat cerebral neurones¹, and with quisqualic acid (Fig. 1d), an ascaricidal compound isolated from seeds of the plant genus Quisqualis⁵. Quisqualic acid is highly potent as a glutamate agonist at the crayfish neuromuscular junction⁶. Compounds were tested on rat spinal interneurones by micro-electrophoresis⁷ and on frog spinal motoneurones by superfusion of the procaine-blocked⁸ hemisected spinal cord in vitro⁹. On both these preparations (see Table 1), the anions of domoic and quisqualic acids were found to be at least two orders of magnitude more potent than L-glutamate, and equal to or stronger than kainate, whereas α-allo-kainate was a considerably weaker excitant.