Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Organic cation transporters (OCTs) are involved in the elimination of monoamines and cationic xenobiotics. To examine whether some cell lines express several different OCTs, we investigated seven human cell lines for the mRNA expression pattern of the human (h) transporters hOCT1, hOCT2 and hOCT3. hOCT1 mRNA was found in all cell lines, six additionally expressed hOCT3 and only two cell lines contained all three hOCTs. 2. Among the three OCTs only for the OCT3 (also designated as 'uptake(2)' or 'extraneuronal monoamine transporter') 'selective' inhibitors are described in the literature. The affinities of the OCT3 inhibitors for the other two OCTs are largely unknown. Therefore, we compared the potencies of eight compounds as inhibitors of hOCT-mediated uptake of the organic cation [(3)H]-1-methyl-4-phenylpyridinium ([(3)H]-MPP(+)) in human embryonic kidney 293 (HEK293) cells stably expressing hOCT1, hOCT2 or hOCT3. Decynium-22 inhibited hOCT3 with 10 fold higher potency than hOCT1 and hOCT2. Corticosterone was about 100 fold more potent as inhibitor of hOCT3 than of hOCT1 or hOCT2, and O-methylisoprenaline (OMI) inhibited almost exclusively hOCT3. Progesterone and beta-Oestradiol preferentially inhibited hOCT3 and hOCT1, whereas prazosin was a potent inhibitor of hOCT1 and hOCT3. Phenoxybenzamine (PbA) inhibited with about equal apparent potency all three hOCTs, whereas the PbA derivative SKF550 ((9-fluorenyl)-N-methyl-beta-chloroethylamine) preferentially inhibited hOCT3 and hOCT2. 3. PbA reversibly inhibited hOCT1 and irreversibly hOCT2 and hOCT3; SKF550 also irreversibly inhibited hOCT3 but hOCT2 in a reversible manner. 4. These compounds enable a functional discrimination of the three hOCTs: hOCT1 is selectively inhibited by prazosin, reversibly inhibited by PbA and it is not sensitive to inhibition by SKF550 and OMI; hOCT2 is reversibly inhibited by SKF550, irreversibly by PbA and not by prazosin, beta-oestradiol and OMI, whereas hOCT3 is selectively inhibited by corticosterone, OMI and decynium22.
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PMID:Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. 1211 Jun 7

The aim of this work was to characterize the uptake of 1-methyl-4-phenylpyridinium (MPP(+)) in the JAR human choriocarcinoma cell line. As JAR cells, as well as the placenta, express the neuronal serotonin transporter (SERT), a comparison between the uptake of (3)H-MPP(+) and (3)H-serotonin ((3)H-5HT) was made. Specific uptake of (3)H-MPP(+) (0.2 microM ) was temperature-, Na(+)- and potential-dependent. 5HT and MPP(+) reduced (3)H-MPP(+) specific uptake (for 5HT, its IC(50) was found to be 4 microM ). The SERT inhibitors desipramine and fluoxetine also inhibited (3)H-MPP(+) specific uptake (with IC(50)s of 189 and 0.92 microM, respectively). The inhibitors of the extraneuronal monoamine transporter (EMT) and of the organic cation transporter type 2 (OCT2), corticosterone and decynium22, had no effect on (3)H-MPP(+) specific uptake, but cyanine863 concentration-dependently reduced it (with an IC(50) of 23 microM ). Specific uptake of (3)H-5HT (0.2 microM ) by JAR cells was temperature-, Na(+)- and potential-dependent. 5HT, MPP(+), desipramine and fluoxetine concentration-dependently inhibited (3)H-5HT specific uptake (with IC(50)s of 1.9 microM, 50 microM, 0.17 microM and 0.046 microM, respectively). Corticosterone showed no effect, but decynium22 and cyanine863 significantly reduced(3) H-5HT specific uptake. For cyanine863, its IC(50) was found to be 11 microM. In conclusion, the results suggest that: (1) uptake of (3)H-5HT by JAR cells occurs exclusively through SERT; (2) uptake of(3) H-MPP(+) by JAR cells involves SERT and also another transporter; (3) neither EMT nor OCT2 are functionally present in JAR cells.
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PMID:Uptake of 1-methyl-4-phenylpyridinium (MPP+) by the JAR human placental choriocarcinoma cell line: comparison with 5-hydroxytryptamine. 1265 10