Regulation of Magnesium Efflux from Rat Spleen Lymphocytes

Rat spleen lymphocytes (RSL) incubated at 37°C in Mg-free medium (0-transconditions) exibited Mg2+efflux with apparent velocity of 0.2 nmol/mg protein/min. After 30 min, this process accounted for the mobilization of about 15% of cell total Mg2+. Half of the Mg2+efflux depended on extracellular Na+and was stimulated by cAMP. IFN-α significantly enhanced Mg2+efflux under0-transconditions as well as in the presence of physiological extracellular Mg2+. Pretreatment of RSL with indomethacin completely abolished IFN-α-induced Mg2+efflux, suggesting a crucial role for cyclo-oxygenase-dependent arachidonate metabolism. On the other hand, pretreatment of RSL with the PKA inhibitor (Rp)8-Br-cAMPS prevented IFN-α stimulation of Mg2+efflux, indicating the involvement of cAMP. Consistently, both IFN-α and exogenous PGE1increased cAMP from 50 to 125 pmol/mg protein. Altogether these results show that IFN-α stimulates Mg2+efflux by activating arachidonate metabolism and synthesis of prostaglandins. By influencing adenylcyclase activity, PGEs can eventually promote cAMP-dependent Mg2+efflux, possibly through the activity of a Na–Mg antiport. In RSL, therefore, magnesium movements can be under the control of IFN-α and, perhaps, of other cytokines, suggesting the involvement of Mg2+in cell response to receptor-mediated stimuli.