Enhancement of tubular organic base accumulation in renal cortical slices by repeated administrations ofTris-hydroxymethyl aminomethane,tromethamol (THAM) to rats of different ages

Summary After repeated THAM administrations to rats of different ages, an enhancement of THAM accumulation in renal cortical slices was observed, except in newborns. This effect can be interpreted as a specific substrate stimulation of the organic base transport system.Acknowledgment. The authors thank MissKarin Müller for technical assistance.     

Effects of long-term feeding of glibenclamide on normal rats

Summary Prolonged administration of glibenclamide decreased blood sugar, liver glycogen and protein and increased liver and serum lipids and organic phosphates of liver in normal rats. A significant weight increase observed in glibenclamide group of rats is attributed to lipid accumulation.     

Calmodulin-associated post-translational regulation of rat organic cation transporter 2 in the kidney is gender dependent

In this work, regulation of organic cation transporter type 2 from rat (rOCT2) stably transfected in HEK293 cells was investigated by microfluorimetry with 4-(4-(dimethylamino)styryl)-N-methylpyridinium as substrate. The transport mediated by rOCT2 was specifically stimulated by PKA, phosphatidylinositol-3-kinase, p56^lck tyrosine kinase, mitogen-extracellular-signal-regulated-kinase-1/2, calmodulin (CaM), and CaM-kinase-II. The regulatory pattern of rOCT2 differs markedly quantitatively and qualitatively from that of other OCT isoforms. Only CaM-dependent upregulation is conserved throughout the OCT family. For this reason, CaM regulation of rOCT2 was also investigated in isolated S3-segments (known to express only rOCT2) of male and female rat proximal tubules. Inhibition of CaM by calmidazolium significantly decreased rOCT2 activity (−49.0 ± 13.6%, n = 4) in male but not female (9.0 ± 13.0%, n = 4) rats. Real-time PCR and Western blot investigations of CaM expression in rat kidneys showed that male animals have significantly higher CaM expression. This is the first study describing post-translational gender-dependent rOCT2 regulation. Received 26 February 2009; accepted 16 March 2009     

Changes with hypertension and maturation in the response of stomach fundus to acetylcholine

The purpose of these experiments was to compare the contractile response to ACh of stomach fundal strips from hypertensive (SHR) and normotensive (WKY) rats during the development of hypertension. The results indicate that the reactivity to ACh is the same in fundal strips from young SHR and WKY rats; however, with maturation strips from WKY rats undergo a reduction in responsiveness which does not occur in the SHR. Therefore, strips from older SHR rats are more reactive to ACh than are those from age matched WKY rats.     

Decreased number of asialoglycoprotein receptors in diabetic BB Wistar rat

Summary The binding of asialoglycoproteins by hepatic binding protein was studied in freshly isolated hepatocytes from genetically diabetic BB Wistar rats. The number of cell surface asialoglycoprotein receptors was dramatically decreased (58,000±38,000 for diabetic rats compared to 267,000±70,000 for normal rats), while the association equilibrium constant was not changed. These results parallel those obtained with streptozotocin-diabetic rats and support the hypothesis that insulin deprivation is responsible for the decrease in the receptor number.     

Developmental exposure to organic lead causes permanent hippocampal damage in Fischer-344 rats

Summary The long-term consequences of neonatal exposure to triethyl lead, the putative neurotoxic metabolite of the anti-knock gasoline additive tetraethyl lead, were examined with respect to central nervous system (CNS) development. We presently report a series of studies in which exposure of neonatal rats to organic lead produces profound CNS damage in adulthood as indicated by dose-dependent, persistent behavioral hyperreactivity as well as dose-dependent, preferential, and permanent damage to the hippocampus. General morphological parameters of brain development were not altered. Pharmacological probes of neurotransmitter system integrity suggested a functional and dose-dependent relationship between this behavioral hyperreactivity and hippocampal damage via cholinergic, but not dopaminergic, pathways. Furthermore, these alterations were not accompanied by long-term alterations in motor activity and were not attributable to the presence of lead in adult neural tissue. Finally, these behavioral, anatomical, and pharmacological indices of developmental exposure to organic lead were dissociable from any effects of early undernutrition. These data collectively indicate that organolead compounds may pose a potent neurotoxic threat to the developing CNS.     

Developmental exposure to organic lead causes permanent hippocampal damage in Fischer-344 rats

The long-term consequences of neonatal exposure to triethyl lead, the putative neurotoxic metabolite of the anti-knock gasoline additive tetraethyl lead, were examined with respect to central nervous system (CNS) development. We presently report a series of studies in which exposure of neonatal rats to organic lead produces profound CNS damage in adulthood as indicated by dose-dependent, persistent behavioral hyperreactivity as well as dose-dependent, preferential, and permanent damage to the hippocampus. General morphological parameters of brain development were not altered. Pharmacological probes of neurotransmitter system integrity suggested a functional and dose-dependent relationship between this behavioral hyperreactivity and hippocampal damage via cholinergic, but not dopaminergic, pathways. Furthermore, these alterations were not accompanied by long-term alterations in motor activity and were not attributable to the presence of lead in adult neural tissue. Finally, these behavioral, anatomical, and pharmacological indices of developmental exposure to organic lead were dissociable from any effects of early undernutrition. These data collectively indicate that organolead compounds may pose a potent neurotoxic threat to the developing CNS.     

Copper metabolism in the LEC rat: Involvement of induction of metallothionein and disposition of zinc and iron

The Cu concentration was about 40 times higher in the liver of LEC (Long-Evans with a cinnamon-like coat color) rats aged 77 days (227.5±21.6 g/g liver) than in Fischer rats (5.2±0.1 g/g liver). However, in the kidney and brain of the LEC rats, Cu concentrations were lower than in these organs of the Fischer rats. Cu concentration in the hepatic metallothionein fraction was about 130 times higher in the LEC rats than in the Fischer rats. The LEC rats showed markedly low concentrations of Cu in the serum and bile. It seems likely that excretion of Cu from the liver into the bile and blood (as ceruloplasmin) is inherently lacking in the LEC rat.     

Changes with hypertension and maturation in the response of stomach fundus to acetylcholine

Summary The purpose of these experiments was to compare the contractile response to ACh of stomach fundal strips from hypertensive (SHR) and normotensive (WKY) rats during the development of hypertension. The results indicate that the reactivity to ACh is the same in fundal strips from young SHR and WKY rats; however, with maturation strips from WKY rats undergo a reduction in responsiveness which does not occur in the SHR. Therefore, strips from older SHR rats are more reactive to ACh than are those from age matched WKY rats.Acknowledgment. The authors wish to acknowledge the assistance of Mark Kunneman and Elaine Hughes. This work was supported by the following grants: American Heart Association (Texas Affiliate) and National Institutes of Health HL 23815, HL 25349 and HL 24585.     

Attenuation of diabetic retinopathy by the molecular chaperone-inducer amino acid analogue canavanine in streptozotocin-diabetic rats

The effect of canavanine treatment on the electroretinograms of healthy and streptozotocin-diabetic rats was studied. The characteristic amplitudes of the a-wave, W₂ and W₃ oscillatory potentials were markedly diminished in the 2-week streptozotocin-diabetic rats compared with those of the control rats. In contrast, the amplitudes of all the responses of the canavanine-pretreated streptozotocin-diabetic rats were practically indistinguishable from those of the control animals. Our results prompt further investigations for the use of amino acid analogues and other inducers of molecular chaperones in easing the chronic consequences of diabetes such as retinopathy. Received 3 June 1998; received after revision 14 August 1998; accepted 14 August 1998     

Zur Biosynthese von Biopterin in Säugetieren

Summary Biosynthesis of biopterin in mice and rats was studied. After vascular injection of¹⁴C-GTP (U) in mice and rats, radioactive biopterin was isolated from the urine. The specific radioactivity of 6-carboxypterin obtained by oxidation of biopterin was proved to be 7/9 that of biopterin. The result definitely shows that biopterin is biosynthesized from GTP in mice and rats, and the sidechain of biopterin is derived directly from the ribose moiety of GTP.     

Paper tools in experimental cultures

The paper studies various functions of Berzelian formulas in European organic chemistry prior to the mid-nineteenth century from a semiotic, historical and epistemological perspective. I argue that chemists applied Berzelian formulas as productive ‘paper tools’ for creating a chemical order in the ‘jungle’ of organic chemistry. Beginning in the late 1820s, chemists applied chemical formulas to build models of the binary constitution of organic compounds in analogy to inorganic compounds. Based on these formula models, they constructed new classifications of organic substances. They further applied Berzelian formulas in a twofold way to experimentally investigate organic chemical reactions: as tools which supplemented laboratory tools and as tools for constructing interpretive models of organic reactions. The scrutiny of chemists' performances with chemical formulas on paper also reveals a dialectic which contributed considerably to the formation of the new experimental culture of synthetic carbon chemistry that emerged between the late 1820s and the early 1840s. In an unintended and unforeseen way, the tools reacted back on the goals of their users and contributed to conceptual development and a shift of scientific objects and practices (‘substitution’) which transcended the originally intended chemical order.     

Absorption of iron from gut into blood: Sex- and time-related studies in rats

Summary As judged from 2-h blood level curves, adult female rats absorbed more Fe^II per cm² of gross duodenal mucosa than adult male rats. By contrast, the 2-h blood level curves per cm² of mucosa of proximal jejunum did not differ significantly in male and female rats although in both sexes, iron was absorbed more efficiently from the duodenum. This research was supported by grant RO1 AM 12381 from the National Institute of arthritis, Diabetes and Digestive and Kidney Diseases, National Institutes of Health.     

Effect of estradiol on aminoacid incorporation into proteins of different hypothalamic areas in prepuberal rats

Summary Estradiol in vitro produces a significant increase in the incorporation of³H-leucine into proteins of the anterior hypothalamic area in prepuberal female rats, 15 and 20 days old, but not in younger animals. The ovarian hormone induced no changes in the protein synthetic activity of middle and posterior hypothalamus and cerebral cortex in prepuberal female rats of different ages. Estradiol did not modify the protein synthesis of the hypothalamus and cerebral cortex in prepuberal male rats.Supported by a grant from the Consejo Nacional de Investigaciones Cientifícas y Técnicas de la República Argentina.     

Features on intracellular calcium distribution in the adipose tissue of spontaneously hypertensive rats (SHR)

Summar The in vitro study of the kinetics of⁴⁵Ca effux from adipose tissue of rats reveale 3 pools of exchangeable calcium. Calcium content in the intracellular pools of adipose tissue of spontaneously hypertensive rats is increased as compared to that in normotensive controls.     

The biliary excretion of [3H] lysergic acid diethylamide in Wistar and gunn rats

Summary The biliary excretion of [³H] LSD was studied in Wistar and homozygous Gunn rats. In Wistar rats approximately 46% of the given dose was recovered from bile in 2.5 h whilst in the homozygous Gunn rat 26% was recovered in the same time period. In both strains the main metabolites were glucuronides.     

Allotransplantation of rat parathyroid glands: Effects of organ culture and transplantation into the adrenal gland

Summary Allotransplantation of fresh, 1 or 2 week cultured parathyroid glands from Wistar rats (AgB²) to Fischer rats (AgB¹) resulted in prompt rejection of the transplant in the muscle site; whereas transplantation into the adrenal site offered slightly prolonged survival, suggesting that the latter is a privileged transplantation site.Acknowledgments. The authors thank Mrs Barbara Lovett for her secretarial assistance.     

Increased Na+-H+ exchanger activity in the ileal brush-border membrane of spontaneously hypertensive rats

In the present study, we have examined the intestinal Na⁺ transport, through the Na⁺-H⁺ exchanger, in ileal brush-border membrane vesicles (BBMV) isolated from spontaneously hypertensive rats (SHR), and normotensive Wistar Kyoto (WKY) rats as a control group. Na⁺ uptake into ileal BBMV was stimulated in the presence of a proton gradient (pH 5.5 inside/pH 7.5 outside) in SHR and WKY rats, resulting in a transient accumulation (overshoot) in both groups of rats. No overshoot was observed in the absence of a pH gradient. The magnitude of the accumulation was significantly higher in SHR than in WKY rats. Uptake of Na⁺ at equilibrium was identical in the presence and the absence of a proton gradient and was not changed in SHR. The use of amiloride inhibited pH gradient-driven Na⁺ uptake in a dose-dependent manner with a Ki of 90 μM and 100 μM for SHR and WKY rats, respectively. The relationship between proton gradient-driven Na⁺ uptake and external Na⁺ concentration was saturable and conformed to Michaelis-Menten kinetics in both SHR and WKY rats. Lineweaver-Burk analysis of the pH gradient-driven Na⁺ uptake indicated values of V_max that were significantly increased in SHR compared to WKY rats (11.4±0.55 nmol/mg/8 s vs. 4.96±0.78 nmol/mg/8 s for SHR and WKY rats, respectively). In contrast, similar K_m values for Na⁺ were found between SHR and WKY rats (4.0±0.2 mM vs. 4.9±0.6 mM for SHR and WKY rats, respectively). These studies show derangement in ileal BBMV Na⁺ transport of SHR, which is characterized by increased Na⁺-H⁺ exchanger activity. Received 18 December 1996; received after revision 3 February 1997; accepted 7 February 1997     

Inter omental-cerebral vascularization induced by omental graft to the rat brain

Summary The omentum of 13 rats were removed from the abdomen and placed directly on the brain. 5–14 days later the omentum and the underlying brain were joined by numerous vascular anastomoses in 9 rats. The purpose of this work was to study the use of omentum to establish extracranial vascularization of the brain.Supported by funds from Grant RR 514 from the Jefferson Medical College General Research Fund.     

Polymerization of phenolic intermediates of pesticides by a fungal enzyme

Summary The fungusRhizoctonia praticola produces an extracellular phenol oxidase (laccase) which polymerizes phenolic intermediates of various pesticides. The enzyme catalyzes the formation of oligomeric products from halogenated phenolic intermediates of phenoxyalkanoate herbicides and from naphtholic products derived from carbamate insecticides. These findings permit further investigations into the mechanism and role of oxidative coupling leading to the incorporation of xenobiotic compounds into soil organic matter.