title: Relaxin Affects Smooth Muscle Biophysical Properties and Mechanical Activity of the Female Mouse Colon.
abstract: The hormone relaxin (RLX) has been reported to influence gastrointestinal motility in mice. However, at present, nothing is known about the effects of RLX on the biophysical properties of the gastrointestinal smooth muscle cells (SMCs). Other than extending previous knowledge of RLX on colonic motility, the purpose of this study was to investigate the ability of the hormone to induce changes in resting membrane potential (RMP) and on sarcolemmal ion channels of colonic SMCs of mice that are related to its mechanical activity. To this aim, we used a combined mechanical and electrophysiological approach. In the mechanical experiments, we observed that RLX caused a decay of the basal tone coupled to an increase of the spontaneous contractions, completely abolished by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (ODQ). The electrophysiological results indicate for the first time that RLX directly affects the SMC biophysical properties inducing hyperpolarization of RMP and cycles of slow hyperpolarization/depolarization oscillations. The effects of RLX on RMP were abolished by ODQ as well as by a specific inhibitor of the cGMP-dependent protein kinase, KT5823. RLX reduced Ca(2+) entry through the voltage-dependent L-type channels and modulated either voltage- or ATP-dependent K(+) channels. These effects were abolished by ODQ, suggesting the involvement of the nitric oxide/guanylate cyclase pathway in the effects of RLX on RMP and ion channel modulation. These actions of RLX on membrane properties may contribute to the regulation of the proximal colon motility by the nitric oxide/cGMP/cGMP-dependent protein kinase pathway.
authors.affiliation: Sections of Physiology (R.S., R.G., E.I., F.F., M.C.B.) and Anatomy and Histology (S.N.), Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Squecco
authors.affiliation: Sections of Physiology (R.S., R.G., E.I., F.F., M.C.B.) and Anatomy and Histology (S.N.), Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors.forename: Rachele
authors.initials: R
authors.lastname: Garella
authors.affiliation: Sections of Physiology (R.S., R.G., E.I., F.F., M.C.B.) and Anatomy and Histology (S.N.), Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors.forename: Eglantina
authors.initials: E
authors.lastname: Idrizaj
authors.affiliation: Sections of Physiology (R.S., R.G., E.I., F.F., M.C.B.) and Anatomy and Histology (S.N.), Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nistri
authors.affiliation: Sections of Physiology (R.S., R.G., E.I., F.F., M.C.B.) and Anatomy and Histology (S.N.), Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Francini
authors.affiliation: Sections of Physiology (R.S., R.G., E.I., F.F., M.C.B.) and Anatomy and Histology (S.N.), Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: Baccari
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005260:Female; D005769:Gastrointestinal Motility; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009197:Myenteric Plexus / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D012065:Relaxin / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism
chemical_list: C494582:1H-(1,2,3)oxadiazolo(4,4-a)quinoxalin-1-one; D020746:Calcium Channels, L-Type; D002227:Carbazoles; D054086:KATP Channels; D010069:Oxadiazoles; D024642:Potassium Channels, Voltage-Gated; D011810:Quinoxalines; D012333:RNA, Messenger; C478103:RXFP1 protein, mouse; D043562:Receptors, G-Protein-Coupled; C073601:KT 5823; D012065:Relaxin; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D002118:Calcium