Relaxin: New Pathophysiological Aspects and Pharmacological Perspectives for an Old Protein

被引:40
作者
Cernaro, Valeria [1 ]
Lacquaniti, Antonio [1 ]
Lupica, Rosaria [1 ]
Buemi, Antoine [1 ]
Trimboli, Domenico [1 ]
Giorgianni, Grazia [2 ]
Bolignano, Davide [3 ]
Buemi, Michele [1 ]
机构
[1] Univ Messina, Dept Internal Med, I-98100 Messina, Italy
[2] Univ Messina, Clin Expt Dept Med & Pharmacol, Endocrinol Sect, I-98100 Messina, Italy
[3] CNR, IBIM, Clin Epidemiol & Physiopathol Renal Dis & Hyperte, I-89100 Reggio Di Calabria, Italy
关键词
relaxin; relaxin family peptide (RXFP) receptors; pleiotropic hormone; new drugs; RECOMBINANT HUMAN RELAXIN; PREGNANCY HORMONE RELAXIN; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; PULMONARY-FIBROSIS; PORCINE RELAXIN; EMERGING ROLE; UP-REGULATION; RAT RELAXIN; IN-VITRO;
D O I
10.1002/med.21277
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Human relaxin-2 (hereafter simply defined as relaxin) is a 6-kDa peptidic hormone best known for the physiological role played during pregnancy in the growth and differentiation of the reproductive tract and in the renal and systemic hemodynamic changes. This factor can also be involved in the pathophysiology of arterial hypertension and heart failure, in the molecular pathways of fibrosis and cancer, and in angiogenesis and bone remodeling. It belongs to the relaxin peptide family, whose members comprehensively exert numerous effects through interaction with different types of receptors, classified as relaxin family peptide (RXFP) receptors (RXFP1, RXFP2, RXFP3, RXFP4). Research looks toward the in-depth examination and complete understanding of relaxin in its various pleiotropic actions. The intent is to evaluate the likelihood of employing this substance for therapeutic purposes, for instance in diseases where a deficit could be part of the underlying pathophysiological mechanisms, also avoiding any adverse effect. Relaxin is already being considered as a promising drug, especially in acute heart failure. A careful study of the different RXFPs and their receptors and the comprehension of all biological activities of these hormones will probably provide new drugs with a potential wide range of therapeutic applications in the near future.
引用
收藏
页码:77 / 105
页数:29
相关论文
共 172 条
  • [1] In Vitro Pharmacological Characterization of RXFP3 Allosterism: An Example of Probe Dependency
    Alvarez-Jaimes, Lily
    Sutton, Steven W.
    Nepomuceno, Diane
    Motley, S. Timothy
    Cik, Miroslav
    Stocking, Emily
    Shoblock, James
    Bonaventure, Pascal
    [J]. PLOS ONE, 2012, 7 (02):
  • [2] [Anonymous], LANCET
  • [3] Relaxin activates the L-arginine nitric oxide pathway in vascular smooth muscle cells in culture
    Bani, D
    Failli, P
    Bello, MG
    Thiemermann, C
    Sacchi, TB
    Bigazzi, M
    Masini, E
    [J]. HYPERTENSION, 1998, 31 (06) : 1240 - 1247
  • [4] Relaxin counteracts asthma-like reaction induced by inhaled antigen in sensitized guinea pigs
    Bani, D
    Ballati, L
    Masini, E
    Bigazzi, M
    Sacchi, TB
    [J]. ENDOCRINOLOGY, 1997, 138 (05) : 1909 - 1915
  • [5] RELAXIN-INDUCED INCREASED CORONARY FLOW-THROUGH STIMULATION OF NITRIC-OXIDE PRODUCTION
    BANISACCHI, T
    BIGAZZI, M
    BANI, D
    MANNAIONI, PF
    MASINI, E
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1995, 116 (01) : 1589 - 1594
  • [6] Structure and Function Relationship of Murine Insulin-like Peptide 5 (INSL5): Free C-Terminus Is Essential for RXFP4 Receptor Binding and Activation
    Begi, Alessia
    Hossain, Mohammed A.
    Shabanpoor, Fazel
    Chan, Linda
    Zhang, Suode
    Bathgate, Ross A. D.
    Tregear, Geoffrey W.
    Wade, John D.
    [J]. BIOCHEMISTRY, 2011, 50 (39) : 8352 - 8361
  • [7] BEILER JM, 1960, ARCH INT PHARMACOD T, V123, P291
  • [8] BELL RJ, 1993, OBSTET GYNECOL, V82, P328
  • [9] Inhibition of markers of hepatic stellate cell activation by the hormone relaxin
    Bennett, RG
    Kharbanda, KK
    Tuma, DJ
    [J]. BIOCHEMICAL PHARMACOLOGY, 2003, 66 (05) : 867 - 874
  • [10] Controlled Extracellular Matrix Degradation in Breast Cancer Tumors Improves Therapy by Trastuzumab
    Beyer, Ines
    Li, Zongyi
    Persson, Jonas
    Liu, Ying
    van Rensburg, Ruan
    Yumul, Roma
    Zhang, Xiao-Bing
    Hung, Mien-Chie
    Lieber, Andre
    [J]. MOLECULAR THERAPY, 2011, 19 (03) : 479 - 489