Ca < sup > 2+ < /sup > -regulated expression of high affinity methylaminoisobutryic acid transport in hippocampal neurons inhibited by riluzole and novel neuroprotective aminothiazoles

Curr Res Physiol. 2023 Oct 14;6:100109. doi: 10.1016/j.crphys.2023.100109. eCollection 2023.ABSTRACTHigh affinity methylaminoisobutyric acid(MeAIB)/glutamine(Gln) transport activity regulated by neuronal firing occurs at the plasma membrane in mature rat hippocampal neuron-enriched cultures. Spontaneous Ca2+-regulated transport activity was similarly inhibited by riluzole, a benzothiazole anticonvulsant agent, and by novel naphthalenyl substituted aminothiazole derivatives such as SKA-378. Here, we report that spontaneous transport activity is stimulated by 4-aminopyridine (4-AP) and that phorbol-myristate acetate (PMA) increases high K+ stimulated transport activity that is inhibited by staurosporine. 4-AP-stimulated spontaneous and PMA-stimulated high K+-induced transport is not present at 7 days in vitro (DIV) and is maximal by DIV∼21. The relative affinity for MeAIB is similar for spontaneous and high K+-stimulated transport (Km ∼ 50 μM) suggesting that a single transporter is involved. While riluzole and SKA-378 inhibit spontaneous transport with equal potency (IC50 ∼ 1 μM), they exhibit decreased (∼3-5 X) potency for 4-AP-stimulated spontaneous transport. Interestingly, high K+-stimulated MeAIB transport displays lower and differential sensitivity to the two compounds. SKA-378-related halogenated derivatives of SKA-75 (SKA-219, SKA-377 and SKA-375) preferentially inhibit high K+-induced expression of MeAIB transport activity at the plasma membrane (IC50 < 2...

Source: Physiological Research - December 18, 2023 Category: Physiology Authors: Jeffrey D Erickson Thomas Kyllo Heike Wulff Source Type: research