Increased expression of CART, nNOS, VIP, PACAP, SP and GAL in enteric neurons of the porcine stomach prepyloric region following hydrochloric acid infusion

Abstract

Introduction. Stomach hyperacidity leads to damage of the mucus/bicarbonate barrier, ulcerations and the development of stomach cancer. Key regulators of the mucosal barrier/luminal acid balance are neurotransmitters secreted by intramural neurons. The aim of the current study was to determine the expression of gastric neuropeptides and nNOS in the porcine stomach following hydrochloric acid instillation. We report on increased expression of enteric neurotransmitters involved in adaptive reaction to an experimentally-induced hyperacidity state. Material and methods. The investigation was conducted on eight 12-18 kg pigs. The influence of intragastric infusion of hydrochloric acid on the expression of cocaine-and amphetamine-regulated transcript peptide (CART), neuronal nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP), substance P (SP) and galanin (GAL) in the submucous and myenteric gastric neurons of the pig has been studied with double immunofluorescence. Results. A mimicked hyperacidity state significantly increased the proportion of enteric neurons immunoreactive to CART, nNOS, VIP, PACAP, SP and GAL in the submucous gastric neurons. In the myenteric plexus, a significant increase of the number of VIP-, CART-and GAL-immunoreactive (IR) neurons was found. Similarly, the percentage of myenteric nNOS-IR and PACAP-IR neurons tended to increase, while the fraction of SP-IR cells did not change. Conclusions. Stomach hyperacidity modifies the expression of the studied neurotransmitters in a specific way depending on the location of the neurons in particular plexuses of the stomach. Increased numbers of neurons expressing CART, nNOS, VIP, PACAP, SP and GAL clearly indicate their regulatory engagement in the restoration of the physiological gastric balance following hyperacidity.

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Physiological and Pathological Processes within the Gastrointestinal Tract: A Review

“…PACAP-IR nerve terminals have been visualized in the striated muscle of the porcine esophagus [23]. In the prepyloric area of the porcine stomach, PACAP-IR neurons have been identified in both submucous and myenteric plexuses, where they constituted only a small percentage of enteric neurons [24]. A similar observation was made in the porcine corpus of the stomach [11].…”

“…The presence of PACAP in the GI tract has been described in various mammal species, including humans [7,10,11,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. However, it should be emphasized that the distribution of PACAP differs between different parts of the GI tract in the same species and shows interspecies differences.…”

“…Rat nerve fibers in the circular and longitudinal muscle layers, myenteric and submucous plexuses and in the mucosa [7] Pig nerve terminals in the striated muscle [23] Human neurons in the myenteric ganglia intraganglionic nerve fibers in the myenteric ganglia nerve fibers in the circular and longitudinal muscle layers [27] [27] [28] Cat nerve fibers in the myenteric ganglia and muscle layers [19] Sheep nerve fibers in the myenteric ganglia and muscle layers [19,33] Ferret nerve fibers in the myenteric ganglia and muscle layers [19] Stomach Rat nerve fibers in the circular and longitudinal muscle layers, myenteric and submucous plexuses and in the mucosa neurons in the myenteric ganglia the enterochromaffin-like (ECL) cells in the mucosa [7,18] [7,18] [17] Mouse nerve fibers in the mucosa nerve fibers in the circular muscle layer in the antrum [19] [20] Pig neurons in the myenteric and submucous plexuses in the corpus and prepyloric area [11,24] Human nerve fibers in the mucosa and muscle layers cells in the gastric glands [19] [28] Cat nerve fibers in the myenteric ganglia, muscle layers and mucosa cells in the gastric glands [19,28] Sheep nerve fibers in the myenteric ganglia and muscle layers [19,33] Ferret nerve fibers in the myenteric ganglia and muscle layers [19] small intestine Rat neurons in the myenteric and submucous plexuses nerve fibers in the circular and longitudinal muscle layers, myenteric and submucous plexuses and in the mucosa [7,9,16] Mouse nerve fibers in the myenteric ganglia and smooth muscle [19] Guinea pig nerve fibers in the circular and longitudinal muscle layers, myenteric and submucous plexuses and around blood vessels of the submucosa neurons in the myenteric ganglia [21,22] Pig neurons in the myenteric plexus, outer submucous plexus, and inner submucous plexus nerve fibers in the mucosa and both muscular layers in the ileum [10][11][12]25,26] human n...…”

Review: Occurrence and Distribution of Galanin in the Physiological and Inflammatory States in the Mammalian Gastrointestinal Tract

“…Many available reports indicate the effect of gastric disorders on GAL presence in ENS. Intragastric supplementation of hydrochloric acid caused an increase in the GAL level in the porcine prepyloric region (33). Administration of acrylamide in pigs resulted in a percentage increase in galaninergic neurons in the cardia, corpus, and pylorus in both enteric plexuses (34).…”

“…This action is probably mediated by GAL2 (46,47). Studies also suggest that GAL may play a role in neuromodulation and neurotransmission (33). It is well known that neuroactive substances secreted from the same neurons can perform similar functions.…”