| Grant number: | 08/58287-5 |
| Support Opportunities: | Research Projects - Thematic Grants |
| Duration: | October 01, 2009 - February 28, 2014 |
| Field of knowledge: | Biological Sciences - Physiology |
| Principal Investigator: | Gerhard Malnic |
| Grantee: | Gerhard Malnic |
| Host Institution: | Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Pesquisadores principais: | Margarida de Mello Aires ; Nancy Amaral Reboucas |
| Associated scholarship(s): | 11/08657-3 - Study of the control exerted by GSK-3beta on nociception signaling in primary afferent nociceptors and glial cells, BP.PD |
Abstract
This thematic project includes projects having in common the study of ion transporters in membranes. Most of these projects focalize the study of epithelial cells of the kidney, with the exception of two, which analyze glial neurons/cells and osteoclasts. In neurons, the effect of phenylpropenes on voltage sensitive sodium channels will be investigated, and in glial cells, purinergic metabotropic receptors will be studied. In osteoclasts, the modulation of the proton pump (H+-ATPase) by calcitonin ++and inhibitors of the reabsorption of bone tissue will be investigated. The remaining projects are also directed mostly to the study of H+ ion transporters, including the Na+/H+ exchangers (NHE1, NHE3, NHE8) as well as vacuolar H+-ATPase, in cells from the different segments of the proximal tubule, as well as from the distaI nephron, including the convolute distaI tubule, connecting segment and collecting tubules. The interaction of H+-ATPase and C1- channels (CFTR and CLC5) will be investigated using siRNA to silence the expression of these channels in proximal tubule cells. The interaction of the Na+/H+ exchanger with the Na+-glucose cotransporter will be investigated in proximal tubules of normal and diabetic rats. The effect of chronic administration of angiotensin II upon the activity, expression and localization of NHEs and H+ -ATPase will be investigated in another series of studies, including the quantification of proteins, mRNA, promoter analysis and establishment of signaling pathways involved in these processes in different cell types. Besides angiotensin lI, the effects of aldosterone, glycocorticoids and atrial natriuretic peptide on cell pH and H+ transporters will be studied. A detailed analysis of the promoter gene of NHE3 and its modulation by angiotensin and acid-base changes will be performed. The role of guanylins (uro- and renoguanylin), angiotensin II and prostaglandin E2 in H+ and K+ transport in renal tubules in vivo will be evaluated using microperfusion techniques of renal tubules. The internalization of angiotensin receptors (ATIR) and their relationship with NHE1 modulation will be evaluated in collecting duct cells. Fusion proteins GST/Cytoplasmic portion of ATIR will be used to identify proteins that interact with AT1R in proximal tubule cells. An additional investigation line will be introduced by a new member of the group, involving the NH3/NH4+ transporters in renal collecting ducts, RhCG and RhBG. These studies will be performed in oocytes injected with specific mRNAs measuring cell and surface pH in order to determine the permeant species across this membrane. Finally, in collaboration with a group of cardiovascular Physiology, renal modifications (transporter expression and vascular reactivity) will be investigated during acute and chronic myocardial infarction in rats. (AU)
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