Response properties of antral mechanosensitive afferent fibers and effects of ionotropic glutamate receptor antagonists.
The ionotropic glutamate receptors N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are present peripherally in the primary sensory afferent neurons innervating the viscera. Multiple studies have reported roles of glutamate receptors in gastric functions. However, no study has previously shown the direct influence of ionotropic glutamate receptor antagonist on vagal sensory neurons. The objective of this study was to investigate the effects of NMDA and AMPA receptor antagonists on mechanotransduction properties of vagal afferent fibers innervating the rat stomach. Action potentials were recorded from the hyponodal vagus nerve innervating the antrum of the Long-Evans rats. For antral distension (AD), a small latex balloon was inserted into the stomach and positioned in the antrum. The antral contractions were recorded with solid-state probe inserted into the water-filled balloon. Antral units were identified to isovolumic (0.2-1 ml) or isobaric AD (5-60 mm Hg). NMDA and AMPA receptor antagonists were injected in a cumulative fashion (1-100 micromol/kg, i.v.). After the conclusion of experiment, the abdomen was opened and receptive field was mapped by probing the serosa of the stomach. Thirty-two fibers were identified to AD. The receptive fields of 26 fibers were located in the posterior part of the antrum. All fibers exhibited spontaneous firing (mean: 7.00+/-0.97 impulses/s). Twenty fibers exhibited a rhythmic firing that was in phase with antral contractions, whereas 12 fibers exhibited non-rhythmic spontaneous firing unrelated to spontaneous antral contraction. Both groups of fibers exhibited a linear increase in responses to graded isovolumic or isobaric distensions. NMDA (memantine HCl and dizocilpine (MK-801)) and AMPA/kainate (6-cyano-7-nitroquinoxaline 2,3-dione; CNQX) receptor antagonists dose-dependently attenuated the mechanotransduction properties of these fibers to AD. However, competitive NMDA antagonist dl-2-amino-5 phosphopentanoic acid (AP-5) had no effect. The study documents that glutamate receptor antagonists can attenuate responses of gastric vagal sensory afferent fibers innervating the distal stomach, offering insight to potential pharmacological agents in the treatment of gastric disorders.
Sengupta
J N
JN
Division of Gastroenterology and Hepatology, MaccFund Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. sengupta@mcw.edu
Petersen
J
J
Peles
S
S
Shaker
R
R
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004106:Dilatation / Q000295:instrumentation / Q000379:methods; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010812:Physical Stimulation / Q000295:instrumentation / Q000379:methods; D011706:Pyloric Antrum / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology; D017833:Visceral Afferents / Q000187:drug effects / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid