title: Relaxin exerts two opposite effects on mechanical activity and nitric oxide synthase expression in the mouse colon.
abstract: 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) NOSβ-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 nNOSβ and endothelial (e) NOS expression in the neurons and decreases nNOSα and eNOS expression in the smooth muscle cells (SMC). We hypothesized that, in the colon, relaxin primarily increases the activity and expression of nNOSβ and eNOS in the neurons, causing a reduction of the muscle tone. The downregulation of nNOSα 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.
authors.affiliation: Department of Physiological Sciences, University of Florence, Florence, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Baccari
authors.forename: C
authors.initials: C
authors.lastname: Traini
authors.forename: R
authors.initials: R
authors.lastname: Garella
authors.forename: G
authors.initials: G
authors.lastname: Cipriani
authors.forename: M G
authors.initials: MG
authors.lastname: Vannucchi
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000098:blood supply / Q000166:cytology / Q000294:innervation / Q000378:metabolism*; D044682:Colon, Ascending / Q000166:cytology / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D044684:Colon, Transverse / Q000166:cytology / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D056885:Interstitial Cells of Cajal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055595:Mechanical Phenomena; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000098:blood supply / Q000166:cytology / Q000294:innervation / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009994:Osmolar Concentration; D012065:Relaxin / Q000378:metabolism*; D013368:Submucous Plexus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D020030:Nitric Oxide Donors; D012065:Relaxin; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D006162:Guanylate Cyclase