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Valproate and Nonsteroidal Anti‐Inflammatory Drugs Reduces the Activity of Electroneutral (Smtn/Slc5a12) and Electrogenic (SMCTe/Slc5a8) Na + /Monocarboxylate Transporters (SMCT).
Author(s) -
Plata Consuelo,
Juárez Maria Eugenia,
Vázquez Norma,
Gamba Gerardo,
Romero Michael F
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1202.12
Subject(s) - naproxen , chemistry , ketoprofen , cotransporter , ibuprofen , propionate , monocarboxylate transporter , butyrate , transporter , biochemistry , pharmacology , chromatography , sodium , biology , medicine , alternative medicine , organic chemistry , pathology , gene , fermentation
The electroneutral (zSMCTn/Slc5a12) and electrogenic (zSMCTe/Slc5a8) Na + /monocarboxylate (MC − ) transporters of zebrafish, move short chain fatty acids, ketone‐bodies, lactate, pyruvate and nicotinate but with clear differences in Na + : MC − stoichiometry and affinity. The affinity of zSMCTn for pyruvate, lactate and nicotinate is lower than zSMCTe (~6, ~10 and ~40 times respectively). It is known that valproate and nonsteroidal anti‐inflammatory drugs, such as ibuprofen, valproate reduce the activity of mammalian SMCTe, but this effect has not been characterized for SMCTn. Using 22 Na + uptake in Xenopus oocytes injected with either zSMCT's or hSMCT cRNA, we evaluated the kinetics of Na + propionate cotransport by SMCT's (hSMCTe, zSMCTe, zSMCTn). We also determined cotransport inhibition by ibuprofen, ketoprofen, naproxen and valproate of these oocytes in presence or absence of propionate. Our results indicate that zSMCTn (Km =830±110μM) has only 3 times less affinity for propionate than zSMCTe (Km =240±50μM) and hSMCTe (Km =200±20μM). Ibuprofen, ketoprofen, naproxen and valproate cause a significant reduction in 22 Na + uptake for zSMCTe, hSMCTe as well as zSMCTn in presence of propionate. Ibuprofen inhibition is more potent for zSMCTn (K i ~200μM) than zSMCTe (K i ~600μM) and hSMCTe (K i ~800μM). These functional and inhibitory differences may help define the binding site for MC − and Na + of SMCT proteins.