Amrinone potentiates catecholamine-induced lipolysis in fat cells

Am&tone, a bipyridine derivative, exerts a positive inotropic action in vitro 11-31 and in viuo 141. In addition, the drug produces a marked relaxation of vascular [5,6] and intestinal [5,7-91 smooth muscle. In patients with cardiac failure the haemodynamic effects of amrinone are accompanied by an increase in plasma fatty acids and glycerol concentration [lo]. The present study was undertaken in order to test the possibility that amrinone may exert a direct stimulatory effect on hormone-sensitive lipolysis in fat cells. This hypothesis is based on the consideration that amrinone inhibits phosphodiesterase activity [3,11,12] and hinders the response to endogenous adenosine [2,9] in various tissues. In fat cells, cyclic AMP formation is an intermediate step in the activation of triglyceride Iipase by hormones and neurotr~s~tte~ interacting with stimulatory recep tors [13]. This activation can be also induced by agents, such as methylxanthines, that act as antagonists at inhibitory membrane receptors coupled to adenylate cyclase and/or increase cyclic AMP levels by inhibiting phosphodiesterase 113-151. Because of these similarities between the actions of amri none and of theophylline, a typical lipolytic methyl xanthine, the influence of the two drugs on lipolysis was compared and their possible interaction at this level was examined. Finally, since activation of Ca2+ flux in vascular [5], intestinal IS, 161 and cardiac muscle 13,171 is involved in the final effects of amrinone, and many results indicate an outstanding role of Ca2+ in the regulation of lipolysis [18,20], the inguence of external Ca2+ concentration on the effects of amrinone was also tested.