Effects of alcohols and food additives on glutamate receptors expressed in Xenopus oocytes: specificity in the inhibition of the receptors.
To study the effects of food additives on glutamate receptors, they were expressed in Xenopus oocytes that received an injection of poly(A)+ mRNAs prepared from rat brain. The response of the receptors elicited by kainate (KA) and N-methyl-D-aspartate (NMDA) was measured electrophysiologically in the presence and absence of food additives. Both responses elicited by KA and NMDA were inhibited similarly by addition of additives such as caffeine, vanillin or saccharin. However, inhibition of KA-elicited response by food additives followed a competitive inhibition scheme with two binding sites, while that of NMDA-elicited response followed a simple noncompetitive inhibition scheme. Inhibition constants of food additives for both responses were more than 1 mM. So it is unlikely that food additives taken with processed food interrupt signal transmission under physiological conditions. The specificity of inhibition of both responses was examined by adding various compounds to the bathing solutions containing the agonist. Increase of the number of hydroxyl groups in alcohols with the chain of three carbon atoms decreased the potency of inhibition. Potency of the inhibition depended on the species of functional groups. The order of potency of the inhibition by compounds with a chain of six carbon atoms was alcohol = diamine > aldehyde > carboxylic acid. Hexanol inhibited the receptors more strongly than (3Z)-hexen-1-ol. NMDA-elicited response showed little selectivity in inhibition by structural isomers of pentanol, while KA-elicited response showed some selectivity in inhibition by the structural isomers.
Aoshima
H
H
Department of Chemistry, Yamaguchi University, Japan.
D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D005503:Food Additives / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects* / Q000648:ultrastructure*; D012333:RNA, Messenger / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors; D017470:Receptors, Glutamate / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors; D012680:Sensitivity and Specificity; D014982:Xenopus laevis
D000438:Alcohols; D018691:Excitatory Amino Acid Antagonists; D005503:Food Additives; D012333:RNA, Messenger; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D007608:Kainic Acid