Evidence that resistin acts on the mechanical responses of the mouse gastric fundus

Abstract

Resistin, among its several actions, has been reported to exert central anorexigenic effects in rodents. Some adipokines which centrally modulate food intake have also been reported to affect the activity of gastric smooth muscle, whose motor responses represent a source of peripheral signals implicated in the control of the hunger-satiety cycle through the gut-brain axis. On this basis, in the present experiments, we investigated whether resistin too could affect the mechanical responses in the mouse longitudinal gastric fundal strips. Electrical field stimulation (EFS) elicited tetrodotoxin- and atropine-sensitive contractile responses. Resistin reduced the amplitude of the EFS-induced contractile responses. This effect was no longer detected in the presence of L-NNA, a nitric oxide (NO) synthesis inhibitor. Resistin did not influence the direct muscular response to methacholine. In the presence of carbachol and guanethidine, EFS elicited inhibitory responses whose amplitude was increased by resistin. L-NNA abolished the inhibitory responses evoked by EFS, indicating their nitrergic nature. In the presence of L-NNA, resistin did not have any effect on the EFS-evoked inhibitory responses. Western blot and immunofluorescence analysis revealed a significant increase in neuronal nitric oxide synthase (nNOS) expression in neurons of the myenteric plexus following resistin exposure. In conclusion, the present results offer the first evidence that resistin acts on the gastric fundus, likely through a modulatory action on the nitrergic neurotransmission.

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

“…As previously observed [23,24], in strips from the mouse gastric fundus, the ad of 1µM carbachol (CCh) to the bath medium (n = 20) caused a rapid rise in contra (mean amplitude 1.1 ± 0.2 g) (Figure 1), which persisted until washout. In CCh-pr tracted strips, electrical field stimulation (EFS, 4 and 8 Hz) elicited a fast relaxant resp which persisted throughout the whole period of stimulation.…”

“…In this view, ADPN and resistin have been reported to affect gastric activity in rodents by exerting inhibitory effects, thereby facilitating smooth muscle relaxation [21][22][23][24]30].…”

“…Endothelial NOS (e-N NOS III), neuronal NOS (nNOS or NOS I) and inducible NOS (iNOS or NOS II) rep the three major isoforms, usually expressed by different cell types [28]. In parti nNOS appears to be the main isoform able to produce NO as a neurotransmitter, w indeed plays the most important role in the control of gastrointestinal motility [25,2 this view, a significant increase in nNOS expression in neurons of the myenteric p following resistin exposure has been revealed in gastric specimens from mice [24].…”

“…In particular, nNOS appears to be the main isoform able to produce NO as a neurotransmitter, which indeed plays the most important role in the control of gastrointestinal motility [25,29]. In this view, a significant increase in nNOS expression in neurons of the myenteric plexus following resistin exposure has been revealed in gastric specimens from mice [24].…”

“…ADPN and resistin, with their different actions, have been reported to also be able to affect gastrointestinal functions [19], including motility [20,21]. In this view, it has been previously observed that in strips from the mouse gastric fundus, ADPN and resistin exert inhibitory effects that appeared to occur, at least in part, through a nitric oxide (NO)-dependent mechanism [21][22][23][24]. Indeed, gastric motility is known to be under hormonal and nervous control.…”