Abstract
BackgroundHuman gastric fundus relaxation is mediated by intrinsic inhibitory pathway. We investigated the roles of nitrergic and purinergic pathways, two known inhibitory factors in gastric motility, on spontaneous and nerve-evoked contractions in human gastric fundus muscles.MethodsGastric fundus muscle strips (12 circular and 13 longitudinal) were obtained from patients without previous gastrointestinal motility disorder who underwent gastrectomy for stomach cancer. Using these specimens, we examined basal tone, peak, amplitude, and frequency of spontaneous contractions, and peak and nadir values under electrical field stimulation (EFS, 150 V, 0.3 ms, 10 Hz, 20 s). To examine responses to purinergic and nitrergic inhibition without cholinergic innervation, atropine (muscarinic antagonist, 1 μM), MRS2500 (a purinergic P2Y1 receptor antagonist, 1 μM), and N-nitro-L-arginine (L-NNA, a nitric oxide synthase inhibitor, 100 μM) were added sequentially for spontaneous and electrically-stimulated contractions. Tetrodotoxin was used to confirm any neuronal involvement.ResultsIn spontaneous contraction, L-NNA increased basal tone and peak in both muscle layers, while amplitude and frequency were unaffected. EFS (up to 10 Hz) uniformly induced initial contraction and subsequent relaxation in a frequency-dependent manner. Atropine abolished initial on-contraction and induced only relaxation during EFS. While MRS2500 showed no additional influence, L-NNA reversed relaxation (p = 0.012 in circular muscle, and p = 0.006 in longitudinal muscle). Tetrodotoxin abolished any EFS-induced motor response.ConclusionsThe relaxation of human gastric fundus muscle is reduced by nitrergic inhibition. Hence, nitrergic pathway appears to be the main mechanism for the human gastric fundus relaxation.
Highlights
Several mechanisms have been suggested to explain the association between the symptoms of functional dyspepsia (FD) and underlying pathophysiology [1,2]
The relaxation of human gastric fundus muscle is reduced by nitrergic inhibition
Numerous studies with animal models have attempted to explain the neurotransmitters involved in this adaptive relaxation. These studies reached upon an agreement that there is more than one neurotransmitter released by the inhibitory neurons, including nitric oxide (NO) [5,6,7,8], vasoactive intestinal polypeptide (VIP) [9,10,11,12], and adenosine triphosphate (ATP) [13,14]
Summary
Several mechanisms have been suggested to explain the association between the symptoms of functional dyspepsia (FD) and underlying pathophysiology [1,2]. Gastric accommodation is activated as the bolus of food reaches the stomach and triggers a reflex largely mediated by intramural intrinsic inhibitory pathways [4]. Numerous studies with animal models have attempted to explain the neurotransmitters involved in this adaptive relaxation. These studies reached upon an agreement that there is more than one neurotransmitter released by the inhibitory neurons, including nitric oxide (NO) [5,6,7,8], vasoactive intestinal polypeptide (VIP) [9,10,11,12], and adenosine triphosphate (ATP) [13,14]. Human gastric fundus relaxation is mediated by intrinsic inhibitory pathway. We investigated the roles of nitrergic and purinergic pathways, two known inhibitory factors in gastric motility, on spontaneous and nerve-evoked contractions in human gastric fundus muscles
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