Potentiation of spontaneous acetylcholine release from motor nerve terminals by glutamate in Xenopus tadpoles.
Extracellular application of glutamate (100 microM) increased the spontaneous secretion of acetylcholine, as well as the amplitude and decay time of miniature endplate potentials at developing neuromuscular synapses in Xenopus tadpoles. Kainate, quisqualate and N-methyl-D-aspartate (100 microM each) increased miniature endplate potential frequency by 26-, 13- and four-fold, respectively. The rank order of efficacy at 100 microM was kainate > quisqualate > N-methyl-D-aspartate > glutamate. The effect of kainate on miniature endplate potential frequency was inhibited by 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (20 microM), but not by (+/-)-2-amino-5-phosphonovalerate (20 microM). Treatment with the voltage-dependent Ca2+ channel blockers verapamil (10 microM), Cd2+ (100 microM) or omega-conotoxin (1 microM) inhibited the potentiating action of kainate on miniature endplate potential frequency. On the other hand, 1S,3R-1-aminocyclopentane-1,3-dicarboxylate (300 microM), a glutamate metabotropic receptor agonist, inhibited the spontaneous acetylcholine release, which was antagonized by the application of 2-amino-3-phosphonopropionate (500 microM). The potentiating effect of glutamate receptor agonists on the miniature endplate potential frequency declined or disappeared in older Xenopus tadpoles. Quisqualate (100 microM) and N-methyl-D-aspartate (100 microM) but not kainate (30 microM) increased the amplitude and decay time of miniature endplate potential, whereas 1S, 3R-1-aminocyclopentane-1, 3-dicarboxylate (300 microM) only increased the decay time of miniature endplate potentials. These results suggest that there are kainate/quisqualate and N-methyl-D-aspartate receptors existing in the motor nerve terminals of younger Xenopus tadpoles and the activation of these receptors potentiates spontaneous acetylcholine release through increasing Ca2+ influx. Our data suggest that the presynaptic glutamate receptors on cholinergic terminals may be involved in feedback regulation of acetylcholine secretion at earlier embryonic stages.
Liou
H C
HC
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Yang
R S
RS
Fu
W M
WM
D000109:Acetylcholine / Q000378:metabolism*; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D007814:Larva; D009045:Motor Endplate / Q000187:drug effects* / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000494:pharmacology; D015290:Second Messenger Systems; D014700:Verapamil / Q000494:pharmacology; D014982:Xenopus laevis / Q000254:growth & development / Q000502:physiology*
D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; C000211:2-amino-3-phosphonopropionic acid; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D014700:Verapamil; D000109:Acetylcholine; D000409:Alanine; D007608:Kainic Acid; D002118:Calcium