Cyclic AMP response to recombinant human relaxin by cultured human endometrial cells—A specific and high throughput in vitro bioassay

Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo.

“…Relaxin binding to its cognate receptor(s) and postreceptor signalling are likely to be complex and cell-and tissue-specific. Relaxin has been reported to enhance cAMP formation in human endometrial (29) and anterior pituitary cells (30), to inhibit Ca 2 ϩ influx in myometrial cells (31) and mast cells (32), and to induce protein kinase C translocation from cytosol to membranes in endometrial cells (33). Additionally, binding of relaxin to certain cell types is estrogen-dependent while binding to others is not (34), and certain phenotypic alterations are dependent on the presence of both relaxin and estrogen while others are not (17).…”

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

“…4). Early studies before receptor identification, showed that treatment with relaxin increased cAMP accumulation in THP-1 cells (Parsell et al, 1996), MCF-7 cells (Bigazzi et al, 1992), the mouse pubic symphysis (Braddon, 1978), uterine strips (Sanborn et al, Relaxin Family Peptide Receptors 1980), uterine longitudinal muscle (Osa et al, 1991) from estrogen-primed rats, and in cultures of human endometrial cells (Fei et al, 1990), human endometrial glandular epithelial cells (Chen et al, 1988), newborn rhesus monkey uterine cells (Kramer et al, 1990), rat myometrial cells (Hsu et al, 1985), and rat anterior pituitary cells (Cronin et al, 1987). The importance of cAMP as a signaling pathway for relaxin was confirmed on RXFP1 deorphanization, because constitutively active mutants of RXFP1 (TM6: D637Y) increased cAMP accumulation in a ligandindependent manner (Hsu et al, 2000.…”

International Union of Pharmacology LVII: Recommendations for the Nomenclature of Receptors for Relaxin Family Peptides

“…Increased intracellular cAMP was observed in mouse pubic symphysis (Braddon, 1978), in rat uterus (Cheah and Sherwood, 1980;Judson et al, 1980;Sanborn et al, 1980), and in cultures of rat (Hsu et al, 1985) and rhesus monkey myometrium (Kramer et al, 1990), human endometrium (Chen et al, 1988;Fei et al, 1990), rat anterior pituitary cell (Cronin et al, 1987), and human THP-1 monocytes (Parsell et al, 1996). The increases in cAMP are important components in relaxininduced myometrial inhibition in the rat (Dodge et al, 1999) and decidualization of human endometrial stromal cells (Huang et al, 1987;Tabanelli et al, 1992).…”