Biomedical subjects

K T Wilson

Publications and source records attributed to K T Wilson.

21 records · Page 2Linked to original sources

PubMed1996

Helicobacter pylori stimulates inducible nitric oxide synthase expression and activity in a murine macrophage cell line.

BACKGROUND & AIMS: Helicobacter pylori uniquely colonizes the human stomach and produces gastric mucosal inflammation. High-output nitric oxide production by inducible nitric oxide synthase (iNOS) is associated with immune activation and tissue injury. Because mononuclear cells comprise a major part of the cellular inflammatory response to H. pylori infection, the ability of H. pylori to induce iNOS in macrophages was assessed. METHODS: H. pylori preparations were added to RAW 264.7 murine macrophages, and iNOS expression was assessed by Northern blot analysis, enzyme activity assay, and NO2- release. RESULTS: Both whole H. pylori and French press lysates induced concentration-dependent NO2- production, with peak levels 20-fold above control. These findings were paralleled by marked increases in iNOS messenger RNA and enzyme activity levels. iNOS expression was synergistically increased with interferon gamma, indicating that the H. pylori effect can be amplified by other macrophage-activating factors. Studies of lipopolysaccharide (LPS) content and polymyxin B inhibition of LPS suggested that the H. pylori effect was attributable to both LPS-dependent and -independent mechanisms. CONCLUSIONS: iNOS expression in macrophages is activated by highly stable H. pylori products and may play an important role in the pathogenesis of H. pylori-associated gastric mucosal disease.

Animals↗

PubMed1996

Production and localization of cGMP and PGE2 in nitroprusside-stimulated rat colonic ion transport.

Nitrovasodilators, such as sodium nitroprusside (SNP), release nitric oxide (NO) and stimulate intestinal electrolyte transport. However, the second messengers involved in this process are unknown. NO stimulates soluble guanylate cyclase activity in other tissues, but stimulation of this enzyme has not previously been described for intestine. We report a 20-fold increase in guanosine 3',5'-cyclic monophosphate (cGMP) production by radioimmunoassay in colonic mucosal strips stimulated with SNP. SNP also caused a significant increase in prostaglandin (PG) E2 release but did not stimulate release of the prostanoids thromboxane B2 or 6-keto-PGF1alpha. Stimulation of isolated colonic crypts and the remaining subepithelial mucosa demonstrated that the latter was the major source of the increases in cGMP and PGE2. Immunostaining of colonic mucosa revealed minimal basal cGMP immunoreactivity but large increases in abundance, localizing to the subepithelium, after SNP treatment. Under basal conditions, there was diffuse immunostaining for constitutive NO synthase in both the epithelial and subepithelial compartments, which was corroborated with NADPH diaphorase staining. In conclusion, SNP was an NO donor stimulates production of cGMP and PGE2 from the subepithelium. NO may be an important mediator of colonic secretion and other processes predominantly via its direct effects on cells of the lamina propria.

1-Methyl-3-isobutylxanthine↗

PubMed1993

Sodium nitroprusside stimulates anion secretion and inhibits sodium chloride absorption in rat colon.

The effects of sodium nitroprusside (SNP) on intestinal electrolyte transport were studied in rat colon mounted in Ussing chambers. Serosal addition of SNP increases short-circuit current (Isc) in a concentration-dependent manner. The maximal change in Isc was 35.6 +/- 2.3 microA/cm2 at 1 mM SNP (ED50 approximately 81 microM). S-nitroso-N-acetylpenicillamine, a nitrosothiol which can release nitric oxide, also stimulated an increase in Isc of 13.9 +/- 3.1 microA/cm2 at a concentration of 100 microM. The response to SNP was rapid, peaking at about 4 min with partial return to baseline at 20 to 30 min. Isc responses to SNP were significantly less in the cecum and ileum as well as after mucosal addition in the distal colon. Pretreatment with serosal atropine, cimetidine, pyrilamine, ketanserin, and N omega-nitro-L-arginine and mucosal amiloride did not inhibit the SNP-stimulated Isc; iodine, methylene blue, bumetanide, piroxicam, and tetrodotoxin each significantly decreased the response and piroxicam plus tetrodotoxin abolished it. Transmural 22Na+ and 36Cl- flux studies demonstrated that the change in Isc produced by SNP was attributable to anion secretion. SNP also inhibited neutral Na+ and Cl- absorption, with the inhibition of Na+, but not Cl- absorption eliminated by tetrodotoxin and piroxicam pretreatment. In summary, SNP has several effects on intestinal electrolyte transport, suggesting that nitric oxide or other components of nitrovasodilators may be important physiological mediators of salt and water transport and may play a role in stimulated colonic epithelial electrolyte transport in inflamed tissues.

Absorption↗