Cynomolgus monkeys (Macaca fascicularis) have been used previously as a model to study effects on cytochrome P450 (CYP) regulation. Until now it has not been elucidated which CYP1A proteins are present in this primate species. The aim of this study was to characterize CYP1A in untreated hepatocytes of cynomolgus monkey using two specific CYP1A inhibitors (alpha-naphthoflavone and furafylline). The effect of different substituted polychlorinated biphenyls (PCBs) on CYP1A regulation was also studied in these hepatocytes. Small quantities of CYP1A2 have been identified in untreated hepatocytes. Northern blots showed the presence of a CYP1A mRNA in untreated hepatocytes, when hybridizations where performed with human CYP1A2 cDNA. Inhibitions with furafylline and alpha-naphthoflavone also suggested the presence of CYP1A2 properties. After induction with different PCBs, (probably) CYP1A1 mRNA and enzyme activity were induced in cynomolgus monkey hepatocytes. As expected, 2,3',4,4',5-PeCB (PCB no. 118), a mono-ortho substituted congener, was a potent CYP1A inducer but 2,2',3,4,4',5',5'-HpCB (PCB no. 180), a di-ortho and 2,2',3,4',5,5',6-HpCB (PCB no. 187), a tri-ortho substituted PCB, could induce CYP1A mRNA and enzyme activity in cynomolgus monkey hepatocytes as well.
Efficacies of the 5‐hydroxytryptamine (serotonin) 5‐HT3 receptor (5‐HT3R) agonists 2‐methyl‐5‐HT, dopamine, and m‐chlorophenylbiguanide on 5‐HT3R native to N1E‐115 cells and on homopentameric 5‐HT3R expressed in Xenopus oocytes were determined relative to that of 5‐HT. Efficacies of 2‐methyl‐5‐HT and dopamine on 5‐HT3R native to differentiated N1E‐115 cells are high (54 and 36%) as compared with their efficacies on homopentameric 5‐HT3R‐AL and 5‐HT3R‐As receptors expressed in oocytes (4–8%). m‐Chlorophenylbiguanide does not distinguish between 5‐HT3R in N1E‐115 cells and in oocytes. The distinct pharmacological profile of 5‐HT3R native to differentiated N1E‐115 cells is conserved when poly(A)+ mRNA from these cells is expressed in oocytes. The results indicate that, apart from the known 5‐HT3R subunits, N1E‐115 cells express additional proteins involved in 5‐HT3R function.
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