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

Abstract

Baccari MC, Traini C, Garella R, Cipriani G, Vannucchi MG. Relaxin exerts two opposite effects on mechanical activity and nitric oxide synthase expression in the mouse colon. Am J Physiol Endocrinol Metab 303: E1142-E1150, 2012. First published August 28, 2012 doi:10.1152/ajpendo.00260.2012.-The hormone relaxin exerts a variety of functions on the smooth muscle of reproductive and nonreproductive organs, most of which occur through a nitric oxide (NO)-mediated mechanism. In the stomach and ileum, relaxin causes muscle relaxation by modulating the activity and expression of different nitric oxide synthase (NOS) isoforms region-dependently. Nothing is known on the effects of relaxin in the colon, the gut region expressing the highest number of neuronal (n) NOS␤-immunoreactive neurons and mainly involved in motor symptoms of pregnancy and menstrual cycle. Therefore, we studied the effects of relaxin exposure in the mouse proximal colon in vitro evaluating muscle mechanical activity and NOS isoform expression. The functional experiments showed that relaxin decreases muscle tone and increases amplitude of spontaneous contractions; the immunohistochemical results showed that relaxin increases nNOS␤ and endothelial (e) NOS expression in the neurons and decreases nNOS␣ and eNOS expression in the smooth muscle cells (SMC). We hypothesized that, in the colon, relaxin primarily increases the activity and expression of nNOS␤ and eNOS in the neurons, causing a reduction of the muscle tone. The downregulation of nNOS␣ and eNOS expression in the SMC associated with increased muscle contractility could be the consequence of continuous exposue of these cells to the NO of neuronal origin. These findings may help to better understand the physiology of NO in the gastrointestinal tract and the role that the "relaxin-NO" system plays in motor disorders such as functional bowel disease. nitric oxide synthase isoforms; nitric oxide synthase splice variants; immunohistochemistry; mechanical responses RELAXIN, a 6,000 Da hormone peptide mainly produced by the corpus luteum, has been shown to exert a variety of physiological effects on the smooth muscle of reproductive and nonreproductive organs, most of which occur through a nitric oxide (NO)-mediated mechanism (1,12,17,33). 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. 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...

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