Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substances known or suspected to cause subtle or transient anatomical alterations in renal development were administered prenatally or neonatally to rats in order to determine whether they are capable of altering renal functional development. Colchicine alters mitotic activity and cytoskeletal structure and is teratogenic in many species. Since the kidney of the newborn rat undergoes extensive cellular proliferation and nephron differentiation, it is possible that neonatal administration of colchicine may affect nephron development. Dinoseb and methyl salicylate have previously been reported to produce a high incidence of dilated renal pelvis in the term rat fetus. Colchicine was injected sc, at 75 micrograms/kg, to Postnatal Day (PD) 1 Sprague-Dawley rats. Dinoseb was administered ip to pregnant Sprague-Dawley rats on Gestation Days 10-12 at doses of 8 or 10.5 mg/kg/day, and methyl salicylate was administered ip at doses of 200, 250, or 300 mg/kg/day on Gestation Days 11-12. Renal function was examined in pups from immediately after birth through weaning. Maximal urine concentrating ability was measured after DDAVP (desmopressin acetate, a vasopressin analog) injection in suckling rats, and after 24 hr of water deprivation in weanlings. Proximal tubule transport was measured in renal cortical slices. Basal urinary parameters, including urine flow, osmolality, pH, and chloride content, were measured. Colchicine treatment had no effect on body weight or kidney weight. There was a significant decrease in maximal urine osmolality in PD 30 rats measured after 24 hr of water deprivation. The urine concentrating deficit detected in functionally mature PD 30 rats suggests that colchicine treatment during renal histogenesis causes a latent deficit in medullary function in the absence of any gross morphological effects. The 10.5 mg/kg/day dose of dinoseb caused a weight reduction in neonates which persisted after weaning. Urine volume after DDAVP challenge was increased over controls in both dose groups on PD 6, but maximal urine concentration was unaffected. On PD 14, maximal urine concentration after DDAVP injection was decreased in the 10.5 mg/kg/day group. By PD 30, urine concentrating ability was comparable to controls. Renal cortical slices from the 10.5 mg/kg/day dose group had an enhanced ability to accumulate organic anions on PD 3 and 31, but opposite effects were observed in the low-dose group. No other renal functional parameters were altered. Urine osmolality after DDAVP challenge was decreased over controls in the 250 mg/kg/day methyl salicylate group on PD 6, and urine volume was increased in this group after DDAVP injection on PD 14.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Functional teratogens of the rat kidney. I. Colchicine, dinoseb, and methyl salicylate. 322 Feb 14

The effects of the herbicides paraquat, dinoseb and 2,4-D on intracellular Ca2+ levels and on vasopressin-induced Ca2+ mobilization were investigated in intact isolated hepatocytes. Incubation of rat hepatocytes with paraquat (5 mM for 60 min) and dinoseb (10 microM) resulted in a time-dependent loss of viability by approximately 25%. Viability of cells treated with 2,4-D decreased significantly, dropping to about 20% at 10 mM and 60 min incubation. Exposure of hepatocytes to paraquat (1-10 mM) for 60 min had no effect on the basal level of [Ca2+]i. Additionally, exposure to paraquat had no effect on the magnitude and on the duration of the [Ca2+]i response to vasopressin. In the presence of 2,4-D (1-10 mM), basal [Ca2+]i increases as a function of herbicide concentration. The magnitude of the delta[Ca2+]i response decreases from 256 +/- 8 nM in control to 220 +/- 5 nM, at 10 mM 2,4-D. Exposure of hepatocytes to dinoseb (1-10 microM) had no effect on the basal level of [Ca2+]i. However, a strong concentration-dependent decrease in the magnitude of delta[Ca2+]i in response to vasopressin was noticed at 60 min incubation. Dinoseb markedly inhibited the stimulation of the production of inositol phosphates by vasopressin stimulus. The present study demonstrates that paraquat, 2,4-D and dinoseb cause cell death in hepatocytes by mechanisms not related to an early increase in [Ca2+]i. Additionally, it has been shown for the first time that dinoseb disturbs the transduction mechanism promoted by vasopressin by inhibiting the formation of IP3.
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PMID:Effects of paraquat, dinoseb and 2,4-D on intracellular calcium and on vasopressin-induced calcium mobilization in isolated hepatocytes. 852 41