Impaired angiotensin II AT(1) receptor function and enhanced Na, K-ATPase affinity for sodium in proximal tubule of streptozotocin-treated diabetic rats.
We determined angiotensin II (Ang II) AT(1) receptor function in terms of Na-K-ATPAse (NKA) stimulation in the proximal tubule (PTs) of streptozotocin-induced diabetic rats. Ang II (10 pM) stimulated NKA activity in PTs of control rats but not diabetic rats. The AT(1) receptor expression was similar, but the expression of G-proteins (G(i)alpha2 and G(i)alpha3) in the PTs was decreased in diabetic compared with control rats. Kinetic studies revealed an increase in NKA affinity, low K(0.5,) for Na, with no changes in V(max) of the enzyme in diabetic compared with control rats. Basal Ser-phosphorylation of NKA alpha1-subunit was lower in diabetic compared with control rats. This data suggest that the higher basal NKA affinity for Na, possibly due to lower Ser-phosphorylaion of alpha1-subunit and not the AT(1) receptor function, in the PTs may be responsible for increased renal Na reabsorption associated with early stage of streptozotocin-induced diabetes.
Siddiqui
Athar H
AH
Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX 77204-5037, USA.
Hussain
Tahir
T
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D015870:Gene Expression; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D013311:Streptozocin / Q000009:adverse effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D013311:Streptozocin; D012964:Sodium; D019204:GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase