Depression by Relaxin of Neurally Induced Contractile Responses in the Mouse Gastric Fundus1

Abstract

The peptide hormone relaxin, which attains high circulating levels during pregnancy, has been shown to depress small-bowel motility through a nitric oxide (NO)-mediated mechanism. In the present study we investigated whether relaxin also influences gastric contractile responses in mice. Female mice in proestrus or estrus were treated for 18 h with relaxin (1 microg s.c.) or vehicle (controls). Mechanical responses of gastric fundal strips were recorded via force-displacement transducers. Evaluation of the expression of nitric oxide synthase (NOS) isoforms was performed by immunohistochemistry and Western blot. In control mice, neurally induced contractile responses elicited by electrical field stimulation (EFS) were reduced in amplitude by addition of relaxin to the organ bath medium. In the presence of the NO synthesis inhibitor l-NNA, relaxin was ineffective. Direct smooth muscle contractile responses were not influenced by relaxin or l-NNA. In strips from relaxin-pretreated mice, the amplitude of neurally induced contractile responses was also reduced in respect to the controls, while that of direct smooth muscle contractions was not. Further addition of relaxin to the bath medium did not influence EFS-induced responses, whereas l-NNA did. An increased expression of NOS I and NOS III was observed in gastric tissues from relaxin-pretreated mice. In conclusion, the peptide hormone relaxin depresses cholinergic contractile responses in the mouse gastric fundus by up-regulating NO biosynthesis at the neural level.

Immunohistochemical and Morphologic Basis for Glutamate Signaling in the Rat Stomach

“…4A) well. NO produced and released by these cells plays a critical role in glutamate signaling in the stomach, as demonstrated by Uneyama et al 2) Baccari et al 6) reported that in the mouse gastric fundus NOS1 immunoreactivity is almost exclusively detected in structures featuring neurons and nerve fibers of the intramural neural plexi. Thus the NOS1-ir cells found in the rat gastric corpus appear to be neurons, although double-labeling immunohistochemical experiments using antibodies to NOS1 and neuronal markers should be carried out.…”

Influence of Relaxin on the Neurally Induced Relaxant Responses of the Mouse Gastric Fundus1

“…In particular, in the gastrointestinal tract, relaxin has been shown to markedly decrease both spontaneous contractions in the ileum [17] and neurally induced cholinergic contractions in the stomach [18].…”

Relaxin exerts two opposite effects on mechanical activity and nitric oxide synthase expression in the mouse colon

“…Interestingly, the depression of muscle contractility reported in the mouse stomach and ileum was mediated by different NOS isoforms. While in the stomach relaxin induced an increase in both the constitutive NOS isoforms, i.e., neuronal (n) NOS and endothelial (e) NOS (3,40), in the ileum it increased the expression of eNOS and of inducible (i) NOS isoforms (8,4). In summary, relaxin is able to act on different NOS isoforms depending on the gut region considered.…”

“…Last, nNOS␣ and full-length eNOS are also expressed by interstitial cells of Cajal (ICC), the gut pacemaker cells. Functionally, NO released by the enteric nerves and/or produced by SMC and ICC acts as an inhibitory mediator, usually causing gastrointestinal relaxation (23,19,31,3,9).The colon is the main gut region involved in motor symptoms accompanying pregnancy and the different phases of menstrual cycle (21, 28). Moreover, the colonic muscle coat contains the highest number of nNOS␤-immunoreactive neurons compared with the other gut regions.…”

“…The latter effects can be direct on the smooth muscle cells (SMC) or mediated by the endothelial cells (2,12,17,30,36). In the gastrointestinal tract, relaxin has been shown to cause depression of muscle contractility by modulating the activity and expression of the different nitric oxide synthase (NOS) isoforms (8,3,4,40). Interestingly, the depression of muscle contractility reported in the mouse stomach and ileum was mediated by different NOS isoforms.…”