Influence between NO and CO in guinea pig stomach fundus

The interaction between carbon monoxide and nitric oxide and their role in modulation of stomach fundus excitability was studied. The presence and colocalization of heme oxygenase 1 (HO-1) and nitric oxide synthase (NOS) was verified in myentheric ganglia by immunohistochemistry. The role of inducible heme oxygenase isoenzyme was investigated after in vivo treatment of animals with CoCl2 (80 mg kg-1 b.w.) injected subcutaneously 24 hours before euthanasia. This treatment resulted in positive staining for the inducible isoform in stomach smooth muscle.

Simultaneous detection of gastric acid and histamine release to unravel the regulation of acid secretion from the guinea pig stomach

Gastric acid secretion is regulated by three primary components that activate the parietal cell: histamine, gastrin, and acetylcholine (ACh). Although much is known about these regulatory components individually, little is known on the interplay of these multiple activators and the degree of regulation they pose on the gastric acid secretion mechanism. We utilized a novel dual-sensing approach, where an iridium oxide sensor was used to monitor pH and a boron-doped diamond electrode was used for the detection of histamine from in vitro guinea pig stomach mucosal sections. Under basal conditions, gastrin was shown to be the main regulatory component of the total acid secretion and directly activated the parietal cell rather than by mediating gastric acid secretion through the release of histamine from the enterochromaffin-like cell, although both pathways were active. Under stimulated conditions with ACh, the gastrin and histamine components of the total acid secretion were not altered compared with levels observed under basal conditions, suggestive that ACh had no direct effect on the enterochromaffin-like cell and G cell. These data identify a new unique approach to investigate the regulation pathways active during acid secretion and the degree that they are utilized to drive total gastric acid secretion. The findings of this study will enhance our understanding on how these signaling mechanisms vary under pathophysiology or therapeutic management.

Effect of motilin on the contractility of gastric smooth muscle via NO pathway in guinea pigs

This study investigates the gastroprokinetic effects of motilin and erythromycin A (EM-A) and its potential mechanism in guinea pigs Cavia porcellus in vitro. Guinea pig stomach strips were mounted under organ baths containing Krebs solution. Motilin, EM-A, Nω-Nitro-L-arginine (L-NNA), L-arginine (L-AA) were added to the bathing solution in a non-cumulative way. Then the effects of motilin and EM-A was studied during electrical field stimulation (EFS) in the absence and presence of L-NNA and L-AA in the gastric anturm and fundus of guinea pigs. In addition, we observed the co-expression of motilin receptors and neuronal nitric oxide synthase (nNOS) in the gastric myenteric plexus of guinea pigs by fluo-immunohistochemistry. The results showed that the circular muscle tissues of the gastric fundus generated on-relaxations and off-contractions with the frequency of 1 - 16 Hz. The on-responses induced a relaxation' partially mediated by the release of nitric oxide (NO) because addition of L-NNA turned the relaxations into cholinergically mediated contractions. The off- contractions were also cholinergically mediated as they disappeared under non-adrenergic, non-cholinergic (NANC) conditions using atropine and guanethidine. In fundic strips, motilin and EM-A induced on-relaxation and off- contraction and both motilin (1 µmol/L) and EM-A (100 µmol/L) may significantly increased on- response and reduced off-response (P < 0.05). And the effects of motilin on strip responses were significantly enhanced compared with EM-A. The on-responses could be reversed into a cholinergically mediated contraction by addition of NOS inhibitors L-NNA. In contrast, administration of substrate of NOS, L-AA, significantly increased on-relaxations and reduced cholinergic motor responses which were induced by motilin or EM-A. However D-arginine (D-AA) did not change the above response induced by motilin or EM-A. In the antral strips, motilin and EM-A only increased off-contractions. The response to motilin and EM-A in the presence of L-NNA did differ from that obtained with L-NNA alone. It showed that both motilin and EM-A could enhance off-contractions induced by L-NNA (P < 0.05). Immunohistochemistry study showed that motilin receptor immunoreactive positive neurons were co-localized with nNOS positive neurons in the gastric myenteric plexus of the guinea pigs. These results suggested that motilin or EM-A modulates gastrointestinal motility which was mediated by activating gastric nervous and NO pathways in guinea pigs gastro-intestinal tract.