Regulation of magnesium efflux from rat spleen lymphocytes.
Rat spleen lymphocytes (RSL) incubated at 37 degrees C in Mg-free medium (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 significantly enhanced Mg2+ efflux under O-trans conditions as well as in the presence of physiological extracellular Mg2+. Pretreatment of RSL with indomethacin completely abolished IFN-alpha-induced Mg2+ efflux, suggesting a crucial role for cyclooxygenase-dependent arachidonate metabolism. On the other hand, pretreatment of RSL with the PKA inhibitor (Rp)8-Br-cAMPS prevented IFN-alpha stimulation of Mg2+ efflux, indicating the involvement of cAMP. Consistently, both IFN-alpha and exogenous PGE1 increased cAMP from 50 to 125 pmol/mg protein. Altogether these results show that IFN-alpha 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-alpha and, perhaps, of other cytokines, suggesting the involvement of Mg2+ in cell response to receptor-mediated stimuli.
Wolf
F I
FI
Institute of General Pathology and Giovanni XXIII Cancer Research Centre, Università Cattolica del Sacro Cuore, Rome, Italy.
Di Francesco
A
A
Covacci
V
V
Cittadini
A
A
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology*; D017136:Ion Transport; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology; D013154:Spleen / Q000166:cytology
D016861:Cyclooxygenase Inhibitors; D016898:Interferon-alpha; D007476:Ionophores; D011453:Prostaglandins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D016718:Arachidonic Acid; D000001:Calcimycin; D003994:Bucladesine; D012964:Sodium; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000527:Alprostadil; D008274:Magnesium; D007213:Indomethacin