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Modulation by cationic amphiphilic drugs of serine base-exchange, phospholipase D and intracellular calcium homeostasis in glioma C6 cells.
Pol. J. Pharmacol. 2002: 54 (5) s.483-493, il., bibliogr. 37 poz.
Hasła klasyfikacyjne GBL:
We aimed to assess the effect of three drugs belonging to amphiphilic cations, imipramine, amitriptyline and propranolol, on lipid synthesis and intracellular calcium homeostasis in glioma C6 cells. Antidepressants, imipramine and amitriptyline, had a stimulatory effect on [14C]serine incorporation into phosphatidylserine. Similar effect was induced by propranolol, antidysrhythmic drug and an antagonist of á-adrenergic receptor, but not by isoproterenol, a selective agonist of this receptor. Stimulation of serine base-exchange activity by amphiphilic cations occured at concentration as low as 5 - 25 ćM that may be reached during clinical treatment. At much higher concentration (250 ćM), those drugs also stimulated phospholipase D-mediated synthesis of [14C]phosphatidylethanol and blocked phorbol ester-induced, protein kinase C-dependent phospholipase D activity. The latter effect already occurred at low (25 ćM) concentration of drugs. We have also shown that treatment of the cells with amphiphilic cations (1 mM) produced only a weak incrase in the intracellular Ca2+ concentration and did not affect Ca2+ release from the intracellular stores evoked by nucleotide receptor agonists, ATP and ADP. In contrast, this treatment strongly diminished an unspecific leak of Ca2+ from the endoplasmic reticulum caused by thapsigarin and ionomycin. Mianserin, which is not cationic amphiphilic drug, did not affect phosphatidylserine synthesis and phospholipase D activity and produced heterogenous and chaotic Ca2+ responses. Our results suggest that imipramine, amitriptyline and propranolol may modulate lipid synthesis and intracellular calcium signaling independently of theis action on membrane receptors, most probably by modification of the physicochemical properties of cell membranes.
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