Experimental diabetes induces increased content of RNA and UTP in the renal cortex. Studies were designed to assess the bioavailability of 5-phosphoribosyl-1-pyrophosphate (PRPP) in the diabetic renal cortex because PRPP is an important determinant of the de novo synthesis of nucleotides. The tissue bioavailability of PRPP determines the effects of orotate or adenine administration on UTP, ATP, and GTP content and on the incorporation of labeled precursors into UTP and ATP. Diabetic and control rats with chronic intravenous cannulas were infused over 2.5-24 h with orotate or adenine. Orotate administration induced greater decreases in ATP and GTP and in labeled adenine incorporation into ATP concomitant with smaller increases in UTP in controls than in diabetic animals. Adenine administration induced a greater decrease of labeled orotate incorporation into UTP and a smaller increase in ATP in controls than in diabetic animals. Prolonging the adenine infusion resulted in disappearance of these differences. The results are compatible with greater initial bioavailability of PRPP in the diabetic renal cortex than in controls but with a rate of maximal PRPP generation that is the same in both tissues.
To evaluate the short-term 24 h urinary excretion of platinum, arsenic, selenium, magnesium and zinc in patients with lung cancer and with cancer other than lungs treated with cisplatin or/and carboplatin from Antofagasta, Chile.Urine measurements of Pt and Se were made by inductively coupled plasma optical emission spectrometry, As by hydride-generation atomic absorption spectrometry and Mg and Zn by means of flame furnace atomic absorption spectrometry.All samples were provided by the Oncological Centre of Antofagasta Regional Hospital (Region of Antofagasta, Chile).Ninety 24-h urine samples from cancer patients after the infusion of Pt-base drugs and 10 24-h urine samples from cancer patients not treated with metal-base drugs.Concentrations of Pt, Se, As, Zn and Mg coming from 24-h urine samples.Pt excreted was not significantly different between patients with lung and other cancers treated with cisplatin. The excretion of Mg, Zn and Se was greater than As. Then, Pt favours the excretion of essential elements. For lung and other types of cancers treated with drugs without Pt, excretion of Mg, Zn and Se was also greater than that of As, suggesting antagonism Mg-Zn-Se-anti-cancer drug relationship.The amounts of Mg, Zn and Se excreted were greater than for As either with or without Pt-containing drugs, suggesting antagonist Mg-Zn-Se-anti-cancer drug relationships. The excretion of As, Mg, Zn and Se is induced by Pt. Knowledge obtained can contribute to understanding the arsenic cancer mechanism and the As-Mg-Zn-Se-Pt inter-element association for lung cancer and other types of cancer.
Cocaine exerts its stimulant effect by inhibiting dopamine (DA) reuptake, leading to increased dopamine signaling. This action is thought to reflect the binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share cocaine’s behavioral actions. Further, recent reports show more potent actions of the drug, implying the existence of a high-affinity receptor for cocaine. We now report high-affinity binding of cocaine associated with the brain acid soluble protein 1 (BASP1) with a dissociation constant (Kd) of 7 nM. Knocking down BASP1 in the striatum inhibits [3H]cocaine binding to striatal synaptosomes. Depleting BASP1 in the nucleus accumbens but not the dorsal striatum diminishes locomotor stimulation in mice. Our findings imply that BASP1 is a pharmacologically relevant receptor for cocaine.
