Abstract

Cadmium and mercury are extremely nephrotoxic and the understanding of their mechanism of action is one essential step in preventing or reversing their detrimental effect on the kidney. This study is designed to provide insights into the action of heavy metals on critically involved in the urinary concentrating process. Using as a model isolated plasma membranes of the rectal gland of the shark, which are an abundant source for this cotransporter, their mechanism of action will be first characterized kinetically with regard tot he ion transport and bumetanide binding sites. Then the amino acid side chains involved in this interaction between heavy metals and the specific reagents with that of the toxins. Finally, the amino acids carrying these heavy metal- sensitive side chains will be localized at the molecular level. These studies will contribute substantially to the understanding of the action of heavy metals at the transporter protein level and thereby provide important information on potential target sites, putative receptors and possible binding motifs of heavy metals and their chemical nature.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Center Core Grants (P30)
Project #
5P30ES003828-15
Application #
6301305
Study Section
Project Start
2000-04-01
Project End
2001-03-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
15
Fiscal Year
2000
Total Cost
$35,639
Indirect Cost

  Institution

Name
Mount Desert Island Biological Lab
Department
Type
DUNS #
City
Salisbury Cove
State
ME
Country
United States
Zip Code
04672

  Publications

Hahn, Mark E; Karchner, Sibel I; Merson, Rebeka R (2017) Diversity as Opportunity: Insights from 600 Million Years of AHR Evolution. Curr Opin Toxicol 2:58-71
Telles, Connor J; Decker, Sarah E; Motley, William W et al. (2016) Functional and molecular identification of a TASK-1 potassium channel regulating chloride secretion through CFTR channels in the shark rectal gland: implications for cystic fibrosis. Am J Physiol Cell Physiol 311:C884-C894
Forrest Jr, John N (2016) THE SHARK RECTAL GLAND MODEL: A CHAMPION OF RECEPTOR MEDIATED CHLORIDE SECRETION THROUGH CFTR. Trans Am Clin Climatol Assoc 127:162-175
Schwarz, Julia S; de Jonge, Hugo R; Forrest Jr, John N (2015) Value of Organoids from Comparative Epithelia Models. Yale J Biol Med 88:367-74
Stahl, Klaus; Stahl, Maximilian; de Jonge, Hugo R et al. (2015) ANP and CNP activate CFTR expressed in Xenopus laevis oocytes by direct activation of PKA. J Recept Signal Transduct Res 35:493-504
Kelley, Catherine A; Decker, Sarah E; Silva, Patricio et al. (2014) Gastric inhibitory peptide, serotonin, and glucagon are unexpected chloride secretagogues in the rectal gland of the skate (Leucoraja erinacea). Am J Physiol Regul Integr Comp Physiol 306:R674-80
De Jonge, Hugo R; Tilly, Ben C; Hogema, Boris M et al. (2014) cGMP inhibition of type 3 phosphodiesterase is the major mechanism by which C-type natriuretic peptide activates CFTR in the shark rectal gland. Am J Physiol Cell Physiol 306:C343-53
Christian, Whitney V; Li, Na; Hinkle, Patricia M et al. (2012) ?-Subunit of the Ost?-Ost? organic solute transporter is required not only for heterodimerization and trafficking but also for function. J Biol Chem 287:21233-43
Barnes, D W (2012) Cell and molecular biology of the spiny dogfish Squalus acanthias and little skate Leucoraja erinacea: insights from in vitro cultured cells. J Fish Biol 80:2089-111
Miller, Hilary D; Clark, Bryan W; Hinton, David E et al. (2012) Anchoring ethinylestradiol induced gene expression changes with testicular morphology and reproductive function in the medaka. PLoS One 7:e52479

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