Influence of relaxin and adiponectin on mice gastrointestinal smooth muscle: mechanical and electrophysiological studies

It is well known that the gastrointestinal (GI) smooth muscle is controlled by nervous, myogenic and hormonal mechanisms. This thesis deals with the effects of the two hormones, relaxin (RLX) and adiponectin (ADPN), on GI smooth muscle of female mice. This choice derives from the statement that RLX, which attains high levels during pregnancy, exerts its effects also beyond the reproductive system and that ADPN, which is mainly produced by the white adipose tissue, has been scarcely investigated concerning on its actions on gastric activity. Particularly, by means of a combined mechanical and electrophysiological approach, the muscular effects of RLX on both colon and ileum and of ADPN on gastric fundus have been tested. Our results demonstrate that both RLX and ADPN are able to influence the mechanical activity and the biophysical properties of GI smooth muscle preparations, causing a decay of the basal tension and, principally, a hyperpolarization of the resting membrane potential. Moreover, the electrophysiological results demonstrate, for the first time, that the two hormones induce similar effects on voltage-dependent Ca2+ current and Ca2+-dependent K+ current (IBK), determining a reduction in size of the amplitude. In contrast, the effects observed on IKs and IKv varied in the different preparations. Furthermore, the analysis of the mechanism of action suggests that RLX is likely to exert its effects through the cGMP signalling pathway in colonic preparations, whereas both cGMP and cAMP seem to be involved in the ileal ones. In conclusions, from a physiological point of view, the myorelaxant effects of RLX on the gut may increase the intestinal transit time, improving water and nutrient absorption. This aspect is particularly important during pregnancy and may also account for the constipation symptom frequently observed in this physiological state. At variance, the relaxant effects induced by ADPN on gastric fundus preparations, may contribute to increase the organ capacity. Since gastric distension represents, a peripheral satiety signal, it could be speculated that the relaxant effects of ADPN might concur to suppress feeding behaviour in rodents. Thus, even if caution is needed when transferring the results obtained in animal models to humans, the present data suggest that ADPN could be regarded as a potential therapeutic tool in the treatment of obesity and eating disorders.