Effects of relaxin on mast cells. In vitro and in vivo studies in rats and guinea pigs.

Abstract

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. (J.

Relaxin‐induced increased coronary flow through stimulation of nitric oxide production

“…In the heart, NO may be generated by various components of the coronary vessels, such as endothelium and smooth muscle cells (Palmer et al, 1988;Mollace et al, 1991), as well as by perivascular mast cells (Masini et al, 1991). In this context, it should be mentioned that mast cells and vascular smooth muscle cells have been shown by us to increase NO production upon RLX treatment (Masini et al, 1994;Bigazzi et al, 1995). In the isolated heart perfused in the Langendorff apparatus, the perfusion fluid does not enter the left ventricle, hence the coronary flow is substantially independent of cardiac activity.…”

“…In recent studies carried out in our laboratory on mast Author for correspondence. cells (Masini et al, 1994), platelets and arterial smooth muscle cells in culture, RLX has been found to stimulate the production of nitric oxide (NO), which is known to be a powerful vasodilator agent (Ignarro et al, 1987;Palmer et al, 1987). Therefore, we were prompted to search for a relationship between possible changes in coronary flow and NO production by the heart upon RLX administration, and to compare the effects of RLX with those exerted by endothelium-dependent and -independent vasodilator agents.…”

Relaxin prevents the development of severe acute pancreatitis

“…refl ected in the histopathology and numerous biochemical parameters that require to be assessed in order to arrive to a proper classifi cation of the disease. It has been reported that relaxin can stimulate the nitric oxide pathway or the glucocorticoid receptor [7,14] . In our work we have evaluated the combined vasorelaxing and anti-infl ammatory properties of relaxin on the evolution of acute pancreatitis, our results show that relaxin plays a highly beneficial role when administered within the first hour of the initiation of the noxa being this even more pronounced when the drug was given 1h pre and 4h post triggering acute pancreatitis, this would be particularly relevant for the prevention of post-ERCP pancreatitis providing basis for future studies where combined drug treatments can be considered.…”

“…It has been shown that relaxin up regulates nitric oxide synthase (NOS) II expression thus inducing nitric oxide mediated vasodilatation by a controlled activation of endogenous nitric oxide biosynthesis [11] . By regulating nitric oxide relaxin inhibits neutrophil extravasation, adhesion, recruitment and activation [12] ; decreases the expression of chemokines and adhesion molecules [13] ; inhibits histamine release by mast cells [14] ; depresses platelet aggregation [15] ; alters Ik-B phosphorylation and degradation diminishing NF-kB activation and binding to DNA and enhances the activation of the glucocorticoid receptor (GR) [16] . Therefore, via the nitric oxide pathway relaxin exerts vasorelaxant, anti-thrombotic and anti-infl ammatory properties.…”

Relaxin Activates the l -Arginine–Nitric Oxide Pathway in Vascular Smooth Muscle Cells in Culture

“…Concerning the mechanism of action of RLX on its target organs, our studies of coronary vessels in the isolated, perfused rat and guinea pig heart 7,8 have shown that the vasodilatory action of RLX is mediated by stimulation of endogenous production of NO, which is a powerful vasorelaxant. 11,12 It is worth noting that stimulation of intrinsic NO production is also involved in the response to RLX in different cells, such as rat and guinea pig serosal mast cells, 13 human and rabbit platelets, 14 and mammary adenocarcinoma MCF-7 cells. 15 There is general agreement that the vasodilatory action of NO is primarily an endothelium-dependent process.…”