Concentration and voltage dependence of Mg transport across the rat duodenum was measured in an Ussing chamber. Mucosa (m) to serosa (s) Mg flux exhibits a cellular fraction comparable to that found for Ca. Mg sm flux is purely diffusive and probably restricted to the paracellular pathway. At all concentrations between 0.5 and 5 mmol/liter, Mg is secreted. Diffuse sm Mg flux is 3.5 times higher than the diffusive component of ms Mg transport. This prevalence of diffusive sm Mg flux over that from mucosa to serosa, which may be explained by an "anomalous solvent drag effect," is responsible for the Mg secretion observed. Mg 5 mmol/liter decreases ms Ca flux and abolishes Ca absorption. The voltage clamp experiments reveal that Mg has no effect on the cellular transport but only decreases diffusive ms Ca flux. 1 alpha,25-dihydroxyvitamin D3 has only a small effect on cellular Mg transport but remarkably stimulates ms Ca flux and increases Ca absorption by about 85%. Dexamethasone increases ms Mg flux but decreases ms Ca transport and hereby abolished Mg secretion or Ca absorption. In conclusion, Mg is secreted across the short-circuited duodenum whereas Ca is absorbed. There is evidence that both earth alkalines are transported by distinct cellular mechanisms. The data also demonstrate that diffusive movement across the paracellular pathway plays an important role on net Mg transport.
The identification of genetic factors underlying individual differences in antipsychotic drug response is of major interest. We investigated the involvement of two norepinephrine transporter gene polymorphisms in response to antipsychotics, comparing patients with strong and weak response to olanzapine and risperidone. We prospectively assessed short-term drug response in 75 Caucasian schizophrenic patients treated with these drugs, using the Positive and Negative Syndrome Scale. We then assessed the association between two SLC6A2 gene polymorphisms and drug response in this sample. No significant difference in genotype distribution was found between responders and non-responders, for the G1287A or T-182C polymorphism. The improvement in PANSS positive subscore was significantly greater in patients homozygous for the A1287 allele than in other patients, and significantly smaller in patients homozygous for the C-182 allele than in other patients. Our results suggest that these polymorphisms are specifically involved in the variation of positive symptoms in schizophrenic patients.
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