The results of the current study demonstrate that relaxin inhibits histamine release by mast cells. This effect is related to the peptide concentrations, and could be observed in both isolated rat serosal mast cells stimulated with compound 48/80 or calcium ionophore A 23187, and in serosal mast cells isolated from sensitized guinea pigs and challenged with the antigen. The morphological findings agree with the functional data, revealing that relaxin attenuates calcium ionophore-induced granule exocytosis by isolated rat serosal mast cells. Similar effects of relaxin have also been recognized in vivo by light microscopic and densitometric analysis of the mesenteric mast cells of rats which received the hormone intraperitoneally 20 min before local treatment of the mesentery with calcium ionophore. Moreover, evidence is provided that relaxin stimulates endogenous production of nitric oxide and attenuates the rise of intracellular Ca2+ concentration induced by calcium ionophore. The experiments with drugs capable of influencing nitric oxide production also provide indirect evidence that the inhibiting effect of relaxin on mast cell histamine release is related to an increased generation of nitric oxide. It is suggested that relaxin may have a physiological role in modulating mast cell function through the L-arginine-nitric oxide pathway.
E Masini, D Bani, M Bigazzi, P F Mannaioni, T Bani-Sacchi
Title and authors | Publication | Year |
---|---|---|
Relaxin in fibrotic ligament diseases: Its regulatory role and mechanism
Yuan S, Guo D, Liang X, Zhang L, Zhang Q, Xie D |
Frontiers in Cell and Developmental Biology | 2023 |
Chronic Exposure to Cigarette Smoke Affects the Ileum and Colon of Guinea Pigs Differently. Relaxin (RLX-2, Serelaxin) Prevents Most Local Damage.
Traini C, Nistri S, Calosi L, Vannucchi MG |
Frontiers in pharmacology | 2022 |
Relaxin peptides reduce cellular damage in cultured brain slices exposed to transient oxygen–glucose deprivation: an effect mediated by nitric oxide
NP DeAdder, HJ Gillam, BC Wilson, MJ Hogan |
2021 | |
Adipokines and Inflammation: Focus on Cardiovascular Diseases
S Feijóo-Bandín, A Aragón-Herrera, S Moraña-Fernández, L Anido-Varela, E Tarazón, E Roselló-Lletí, M Portolés, I Moscoso, O Gualillo, JR González-Juanatey, F Lago |
International journal of molecular sciences | 2020 |
Cardioprotective actions of relaxin
B Martin, G Romero, G Salama |
Molecular and Cellular Endocrinology | 2019 |
Relaxin and extracellular matrix remodeling: Mechanisms and signaling pathways
HH Ng, M Shen, CS Samuel, J Schlossmann, RG Bennett |
Molecular and Cellular Endocrinology | 2019 |
Understanding relaxin signalling at the cellular level
AL Valkovic, RA Bathgate, CS Samuel, M Kocan |
Molecular and Cellular Endocrinology | 2018 |
A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1
MA Hossain, M Kocan, ST Yao, SG Royce, VB Nair, C Siwek, NA Patil, IP Harrison, KJ Rosengren, S Selemidis, RJ Summers, JD Wade, RA Bathgate, CS Samuel |
Chemical Science | 2016 |
Protection from Cigarette Smoke-Induced Lung Dysfunction and Damage by H2 Relaxin (Serelaxin)
A Pini, G Boccalini, L Lucarini, S Catarinicchia, D Guasti, E Masini, D Bani, S Nistri |
The Journal of pharmacology and experimental therapeutics | 2016 |
Novel therapeutic strategies for lung disorders associated with airway remodelling and fibrosis
SG Royce, Y Moodley, CS Samuel |
Pharmacology & Therapeutics | 2014 |
Intranasally administered serelaxin abrogates airway remodelling and attenuates airway hyperresponsiveness in allergic airways disease
SG Royce, CX Lim, KP Patel, B Wang, CS Samuel, ML Tang |
Clinical & Experimental Allergy | 2014 |
Relaxin Family Peptides and Their Receptors
RA Bathgate, ML Halls, ET van der Westhuizen, GE Callander, M Kocan, RJ Summers |
Physiological reviews | 2013 |
Disturbed relaxin signaling pathway and testicular dysfunction in mouse offspring upon maternal exposure to simazine
HO Park, J Bae |
PloS one | 2012 |
Disturbed Relaxin Signaling Pathway and Testicular Dysfunction in Mouse Offspring upon Maternal Exposure to Simazine
HO Park, J Bae, SR Singh |
PloS one | 2012 |
Relaxin inhibits early steps in vascular inflammation
A Brecht, C Bartsch, G Baumann, K Stangl, T Dschietzig |
Regulatory Peptides | 2011 |
Relaxin is a candidate drug for lung preservation: Relaxin-induced protection of rat lungs from ischemia-reperfusion injury
K Alexiou, K Matschke, A Westphal, K Stangl, T Dschietzig |
The Journal of Heart and Lung Transplantation | 2010 |
Mast cells, peptides and cardioprotection - an unlikely marriage?
SK Walsh, KA Kane, CL Wainwright |
Autonomic and Autacoid Pharmacology | 2009 |
Relaxin Promotes Clustering, Migration, and Activation States of Mononuclear Myelocytic Cells
KA Figueiredo, G Rossi, ME Cox |
Annals of the New York Academy of Sciences | 2009 |
An in Vitro Study of the Protective Effect of Relaxin on Brain Tissue under Ischemic Stress
BC Wilson, R Rappaport |
Annals of the New York Academy of Sciences | 2009 |
Glucocorticoids inhibit degranulation of mast cells in allergic asthma via nongenomic mechanism
J Zhou, DF Liu, C Liu, ZM Kang, XH Shen, YZ Chen, T Xu, CL Jiang |
Allergy | 2008 |
Relaxin induces mast cell inhibition and reduces ventricular arrhythmias in a swine model of acute myocardial infarction
S Nistri, L Cinci, AM Perna, E Masini, R Mastroianni, D Bani |
Pharmacological Research | 2008 |
Relaxin and Related Peptides
AI Agoulnik |
2007 | |
Relaxin and Related Peptides
AI Agoulnik |
2007 | |
Relaxin Antagonizes Hypertrophy and Apoptosis in Neonatal Rat Cardiomyocytes
X Moore, S Tan, C Lo, L Fang, YD Su, XM Gao, EA Woodcock, RJ Summers, GW Tregear, RA Bathgate, XJ Du |
Endocrinology | 2007 |
Relaxin—a pleiotropic hormone and its emerging role for experimental and clinical therapeutics
T Dschietzig, C Bartsch, G Baumann, K Stangl |
Pharmacology & Therapeutics | 2006 |
Cardiac anaphylaxis: Pathophysiology and therapeutic perspectives
D Bani, S Nistri, PF Mannaioni, E Masini |
Current Allergy and Asthma Reports | 2006 |
‘Relaxin’ the stiffened heart and arteries: The therapeutic potential for relaxin in the treatment of cardiovascular disease
CS Samuel, XJ Du, RA Bathgate, RJ Summers |
Pharmacology & Therapeutics | 2006 |
Relaxin-induced reduction of infarct size in male rats receiving MCAO is dependent on nitric oxide synthesis and not estrogenic mechanisms
BC Wilson, B Connell, TM Saleh |
Neuroscience Letters | 2006 |
Relaxin prevents the development of severe acute pancreatitis
LI Cosen-Binker, MG Binker, R Cosen, G Negri, O Tiscornia |
World journal of gastroenterology : WJG | 2006 |
Reduction of antigen-induced respiratory abnormalities and airway inflammation in sensitized guinea pigs by a superoxide dismutase mimetic
E Masini, D Bani, A Vannacci, S Pierpaoli, PF Mannaioni, SA Comhair, W Xu, C Muscoli, SC Erzurum, D Salvemini |
Free radical biology & medicine | 2005 |
New Insights into Biological Roles of Relaxin and Relaxin-related Peptides
JI Park, CL Chang, SY Hsu |
Reviews in Endocrine and Metabolic Disorders | 2005 |
Gene expression profiling of dexamethasone-treated RBL-2H3 cells: induction of anti-inflammatory molecules
R Nakamura, H Okunuki, S Ishida, Y Saito, R Teshima, J Sawada |
Immunology Letters | 2005 |
Basic Progress and Future Therapeutic Perspectives of Relaxin in Ischemic Heart Disease
D Bani, S Nistri, TB Sacchi, M Bigazzi |
Annals of the New York Academy of Sciences | 2005 |
Relaxin Stimulates Leukocyte Adhesion and Migration through a Relaxin Receptor LGR7-dependent Mechanism
KA Figueiredo, AL Mui, CC Nelson, ME Cox |
The Journal of biological chemistry | 2005 |
Novel drug development opportunity for relaxin in acute myocardial infarction: evidences from a swine model
AM Perna, E Masini, S Nistri, V Briganti, L Chiappini, P Stefano, M Bigazzi, C Pieroni, TB Sacchi, D Bani |
The FASEB Journal | 2005 |
Relaxin’s Physiological Roles and Other Diverse Actions
OD Sherwood |
Endocrine reviews | 2004 |
Effect of a plant histaminase on asthmalike reaction induced by inhaled antigen in sensitized guinea pig
E Masini, A Vannacci, L Giannini, O Befani, S Nistri, MA Mateescu, PF Mannaioni, B Mondovì, R Federico |
European Journal of Pharmacology | 2004 |
Emerging role of relaxin in renal and cardiovascular function
KP Conrad, J Novak |
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology | 2004 |
Relaxin Inhibits the Activation of Human Neutrophils: Involvement of the Nitric Oxide Pathway
E Masini, S Nistri, A Vannacci, TB Sacchi, A Novelli, D Bani |
Endocrinology | 2004 |
Protective effect of relaxin in cardiac anaphylaxis: involvement of the nitric oxide pathway
E Masini, G Zagli, JF Ndisang, M Solazzo, PF Mannaioni, D Bani |
British Journal of Pharmacology | 2002 |
Inhibitory effects of relaxin on human basophils activated by stimulation of the Fcε receptor. The role of nitric oxide
D Bani, R Baronti, A Vannacci, M Bigazzi, TB Sacchi, PF Mannaioni, E Masini |
International Immunopharmacology | 2002 |
A plant histaminase modulates cardiac anaphylactic response in guinea pig
E Masini, A Vannacci, C Marzocca, PF Mannaioni, O Befani, R Federico, A Toma, B Mondovı̀ |
Biochemical and Biophysical Research Communications | 2002 |
Relaxin Depresses Small Bowel Motility Through a Nitric Oxide-Mediated Mechanism. Studies in Mice1
D Bani, MC Baccari, S Quattrone, S Nistri, F Calamai, M Bigazzi, TB Sacchi |
Biology of reproduction | 2002 |
Heme Oxygenase in Biology and Medicine
NG Abraham |
2002 | |
Haeme oxygenase-1 and cardiac anaphylaxis
JF Ndisang, R Wang, A Vannacci, C Marzocca, O Fantappiè, R Mazzanti, PF Mannaioni, E Masini |
British Journal of Pharmacology | 2001 |
Mast cells as a source and target for nitric oxide
M Bidri, F Féger, S Varadaradjalou, NB Hamouda, JJ Guillosson, M Arock |
International Immunopharmacology | 2001 |
Recombinant Relaxin: A Review of Pharmacology and Potential Therapeutic Use
ES Gavino, DE Furst |
BioDrugs | 2001 |
Modulation of the immunological response of guinea pig mast cells by carbon monoxide
JF Ndisang, P Gai, L Berni, C Mirabella, R Baronti, PF Mannaioni, E Masini |
Immunopharmacology | 1999 |
Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart
D Bani, E Masini, MG Bello, M Bigazzi, TB Sacchi |
The American Journal of Pathology | 1998 |
Characterization of gene expression in resting and activated mast cells
H Chen, M Centola, SF Altschul, H Metzger |
Journal of Experimental Medicine | 1998 |
Characterization of Gene Expression in Resting and Activated Mast Cells
H Chen, M Centola, SF Altschul, H Metzger |
Journal of Experimental Medicine | 1998 |
Relaxin Activates the l -Arginine–Nitric Oxide Pathway in Vascular Smooth Muscle Cells in Culture
D Bani, P Failli, MG Bello, C Thiemermann, TB Sacchi, M Bigazzi, E Masini |
Hypertension | 1998 |
Evidence That Relaxin’s Effects on Growth and Softening of the Cervix Are Not Mediated through Prostaglandins in the Rat*
OD Sherwood, ES Jungheim, JL Masferrer, JM Cramer |
Endocrinology | 1998 |
The effect of ketotifen on nitric oxide synthase activity
SN Heyman, F Karmeli, M Brezis, D Rachmilewitz |
British Journal of Pharmacology | 1997 |
Relaxin Counteracts Myocardial Damage Induced by Ischemia-Reperfusion in Isolated Guinea Pig Hearts: Evidence for an Involvement of Nitric Oxide*
E Masini, D Bani, MG Bello, M Bigazzi, PF Mannaioni, TB Sacchi |
Endocrinology | 1997 |
Relaxin Counteracts Asthma-Like Reaction Induced by Inhaled Antigen in Sensitized Guinea Pigs*
D Bani, L Ballati, E Masini, M Bigazzi, TB Sacchi |
Endocrinology | 1997 |
Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo
EN Unemori, LB Pickford, AL Salles, CE Piercy, BH Grove, ME Erikson, EP Amento |
Journal of Clinical Investigation | 1996 |
The effect of relaxin on myocardial ischaemia-reperfusion injury and histamine release in vitro and in vivo
E Masini, D Salvemini, L Mugnai, MG Bello, D Bani, PF Mannaioni |
Inflammation Research | 1996 |
Relaxin Binds to and Elicits a Response from Cells of the Human Monocytic Cell Line, THP-1
DA Parsell, JY Mak, EP Amento, EN Unemori |
The Journal of biological chemistry | 1996 |
Original Article: Relaxin Reduces the Number of Circulating Platelets and Depresses Platelet Release from Megakaryocytes: Studies in Rats
D Bani, M Maurizi, M Bigazzi |
Platelets | 1995 |
Relaxin-induced increased coronary flow through stimulation of nitric oxide production
T Bani-Sacchi, M Bigazzi, D Bani, PF Mannaioni, E Masini |
British Journal of Pharmacology | 1995 |
Renal Sodium Excretion and Edematous Disorders
PY Martin, RW Schrier |
Endocrinology and metabolism clinics of North America | 1995 |