Evidence for a glutamatergic neural pathway in the myenteric plexus.
The objective of this study was to determine whether L-glutamate (L-Glu) may serve as a neurotransmitter candidate in the guinea pig myenteric plexus. We observed that [3H]Glu and gamma-[3H]aminobutyric acid were synthesized from [3H]glutamine and released from neurons of the myenteric plexus during K+ and 1,1-dimethyl-4-phenylpiperazinium-evoked depolarization in a concentration-dependent manner. Muscle tension studies performed on ileal longitudinal muscle-myenteric plexus (LM-MP) preparations revealed that L-Glu [mean effective dose (ED50) 2.5 x 10(-5) M] produced concentration-dependent contractions, which were unaffected by hexamethonium but abolished by tetrodotoxin, atropine, and magnesium, suggesting that L-Glu acts via N-methyl-D-aspartate (NMDA)-type receptors that stimulate a cholinergic neural pathway unaffected by ganglionic blockade. In addition, L-Glu (ED50 4 x 10(-5) M) and NMDA (ED50 2 x 10(-4) M) stimulated concentration-dependent release of [3H]acetylcholine (ACh) from LM-MP sections, which was inhibited by tetrodotoxin, magnesium, and the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (AP-5). L-Glu-mediated release of [3H]ACh was enhanced by theophylline (10-6 M) and 3-isobutyl-1-methylxanthine (1 mM) and was significantly reduced by the adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (10(-4) M) and somatostatin-14 (10(-6) M), which inhibits adenosine 3',5'-cyclic monophosphate (cAMP)-dependent cholinergic transmission in the myenteric plexus. These studies suggest that L-Glu may serve as an excitatory neurotransmitter in the myenteric plexus via its action on NMDA-type receptors, which are coupled to cAMP-dependent release of ACh.
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.
J W
JW
Wiley
Y X
YX
Lu
C
C
Owyang
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D004594:Electrophysiology; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction; D009197:Myenteric Plexus / Q000378:metabolism / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000502:physiology; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005971:Glutamates; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000242:Cyclic AMP; D000109:Acetylcholine