Differential regulation of mammalian brain-specific proline transporter by calcium and calcium-dependent protein kinases
Autor: | L D, Jayanthi, J J, Wilson, J, Montalvo, L J, DeFelice |
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Rok vydání: | 2000 |
Předmět: |
Brain Chemistry
DNA Complementary Down-Regulation Enzyme Activators Membrane Transport Proteins Kidney Transfection Synaptic Transmission Cell Line Amino Acid Transport Systems Neutral Calcium-Calmodulin-Dependent Protein Kinases Papers Humans Tetradecanoylphorbol Acetate Thapsigargin natural sciences Calcium Indicators and Reagents Enzyme Inhibitors |
Zdroj: | British journal of pharmacology. 129(3) |
ISSN: | 0007-1188 |
Popis: | 1. This study examined the role of [Ca2+]I and Ca(2+)-dependent kinases in the modulation of high-affinity, mammalian brain-specific L-proline transporter (PROT). 2. beta-PMA (phorbol 12-myristate 13-acetate), an activator of protein kinase C (PKC), inhibits PRO uptake, and bisindolymalemide I (BIM), a potent PKC inhibitor, prevents beta-PMA inhibition. Down-regulation of PKC by chronic treatment with beta-PMA enhances PROT function indicating PROT regulation by tonic activity of PKC. 3. Thapsigargin, which increases [Ca2+]I levels by inhibiting Ca(2+)-ATPase, inhibits PROT and exhibits additive inhibition when co-treated with beta-PMA. KN-62, a Ca2+/calmodulin-dependent kinase II (CaMK II) inhibitor, but not BIM (a PKC inhibitor) prevents the inhibition by thapsigargin. These data suggest that PKC and CaMK II modulate PROT and that thapsigargin mediates its effect via CaMK II. 4. Thapsigargin raises [Ca2+]I and increases PRO-induced current on a second time scale, whereas the inhibitory effect of thapsigargin occurs only after 10 min of treatment. These data suggest that Ca2+ differentially regulate PROT: Ca2+ initially enhances PRO transport but eventually inhibits transport function through CaMK II pathway. 5. Ca(2+)-induced stimulation exemplifies the acute regulation of a neurotransmitter transporter, which may play a critical role in the profile of neurotransmitters during synaptic transmission. |
Databáze: | OpenAIRE |
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