Neuronal Nitric Oxide Synthase as a Shared Target for the Effects of Adiponectin and Resistin on the Mechanical Responses of the Mouse Gastric Fundus

Abstract

It has been reported that adiponectin (ADPN) and resistin are co-secreted by white mouse adipocytes and exert similar inhibitory effects in the mouse gastric fundus, in which resistin was observed to increase neuronal nitric oxide synthase (nNOS) expression. On these grounds, the present work aimed to investigate whether the effects of the two adipokines on the neurally-induced relaxant responses potentiate each other and whether there is a possible correlation with changes in nNOS expression in preparations from the mouse gastric fundus. In carbachol (CCh)-precontracted strips, electrical field stimulation elicited nitrergic relaxant responses, whose amplitude was increased by ADPN or resistin, but no additional enhancements were observed in their concomitant presence. Western blot and immunofluorescence analyses revealed that ADPN, like resistin, was able to up-regulate nNOS expression and to increase the percentage of nNOS-positive neurons in the myenteric plexus: co-treatment with the two adipokines did not induce additional changes. The results indicate that the two adipokines modulate nitrergic neurotransmission, and both do so by up-regulating nNOS expression. Therefore, nNOS appears to be a shared target for the two adipokines’ effects, which, rather than mutually reinforcing each other, may represent a dual physiological control mechanism to guarantee gastric fundus relaxation.

Adipokines as Possible Players in Inflammatory Bowel Disease: Electrophysiological Evaluation of Their Role in Causing Functional Gastrointestinal Alterations in Murine Tissue

“…Although negative, this outcome adds a piece of knowledge to the complex mechanism of action of RES, supporting the role of this hormone in gastrointestinal distention, as observed in IBD, attributable at the moment only to neuronal NOS activation and NO production [41], without a direct effect on SMCs. The final downstream effectors have yet to be clarified: further investigations could be directed to test the role of reactive oxygen and nitrogen species and cGMP-independent NO signaling pathways triggered by RES.…”

Microbiome profiling and Co-metabolism pathway analysis in cervical cancer patients with acute radiation enteritis

“…The primary role of nitric oxide synthase (NOS) is catalysis of NADPH-dependent l -arginine and O 2 to provide NO and citrulline. However, all isoforms of NOS also produce superoxide (O 2 − ) [ 27 ], forming neuronal (nNOS, NOS-1) and inducing (iNOS, NOS-2) to produce O 2 - continuously, the latter of which consumes l -arginine as the main product [ 28 ]. NOS is stimulated to produce NO by ionizing radiation, thus causing temporary depletion of l -arginine in some microenvironments; this results in increased O 2 − production which cannot be effectively cleared by endogenous superoxide dismutase (SOD).…”