REGULATION OF MAGNESIUM EFFLUX FROM RAT SPLEEN LYMPHOCYTES

Rat spleen lymphocytes (RSL) incubated at 37 degrees C in Mg-free medi um (O-trans conditions) 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-alpha s ignificantly enhanced Mg2+ efflux under O-trans conditions as well as in the presence of physiological extracellular Mg2+. Pretreatment of R SL with indomethacin completely abolished IFN-alpha-induced Mg2+ efflu x, suggesting a crucial role for cyclooxygenase dependent arachidonate metabolism. On the other hand, pretreatment of RSL with the PKA inhib itor (Rp)8-Br-cAMPS prevented IFN-alpha stimulation of Mg2+ efflux, in dicating the involvement of cAMP. Consistently, both IFN-alpha and exo genous PGE(1) increased cAMP from 50 to 125 pmol/mg protein. Altogethe r these results show that IFN-alpha stimulates Mg2+ efflux by activati ng arachidonate metabolism and synthesis of prostaglandins. By influen cing adenylcyclase activity, PGEs can eventually promote cAMP-dependen t Mg2+ efflux, possibly through the activity of a Na-Mg antiport. In R SL, therefore, magnesium movements can be under the control of IFN-LU and, perhaps, of other cytokines, suggesting the involvement of Mg2+ i n cell response to receptor-mediated stimuli. (C) 1997 Academic Press.