Excitatory amino acid receptor-mediated activation of solitarial deglutitive loci.
The deglutitive actions of glutamate were investigated in urethane-anaesthetised rats in order to determine whether different excitatory amino acid receptors mediate activation of pattern generator elements contained within the nucleus tractus solitarii. When applied by micropneumophoresis (0.01-10 pmol) from multibarrelled glass micropipettes (tip diameter 2-5 microns), the excitatory amino acid-receptor agonists, N-methyl-D, L-aspartate (NMA), N-methyl-D-aspartate (NMDA), quisqualate and kainate displayed a rank order of potency at glutamate-responsive pharyngeal sites, in the subnuclei ventralis and intermedialis, where KA greater than NMA/NMDA greater than QA; however, the potency followed the order NMA/NMDA greater than KA greater than QA at oesophageal sites within the subnucleus centralis. The NMDA-receptor blockers, 2-amino-5-phosphonovaleric acid (APV) and 2-amino-7-phosphonoheptanoic acid (AP7), selectively and reversibly inhibited the glutamate-evoked oesophageal responses, but had no corresponding effect on rhythmic oesophageal responses elicited by muscarine. At loci in the nucleus tractus solitarius, where glutamate elicited a complete swallowing sequence, APV/AP7 spared the pharyngeal component but selectively blocked the oesophageal component. The nonselective glutamate-receptor antagonist, gamma-D-glutamylglycine suppressed both pharyngeal and oesophageal responses elicited by glutamate. It is concluded that different types of excitatory amino acid receptors are associated with the deglutitive premotor subnuclei of the nucleus tractus solitarii; kainate receptors predominate within the subnuclei ventralis and intermedialis and NMDA receptors within the subnucleus centralis. Both kainate- and NMDA-mediated mechanisms can operate under physiological conditions.
Hashim
M A
MA
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, Canada.
Bieger
D
D
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000502:physiology; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D003679:Deglutition / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology; D004947:Esophagus / Q000187:drug effects / Q000502:physiology; D005971:Glutamates / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology; D010614:Pharynx / Q000187:drug effects / Q000502:physiology; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000502:physiology*
D000596:Amino Acids; D004151:Dipeptides; D005971:Glutamates; D010069:Oxadiazoles; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; C028929:gamma-glutamylglycine; D001224:Aspartic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; D007608:Kainic Acid