OAT1Organic Anion Transporter 1
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In addition, thymoquinone has also been shown to increase the expression of various organic anion and cation transporters such as OAT1, OAT3, OCT1, and OCT2, which are necessary for the renal clearance of xenobiotic agents including toxins and commonly used drugs [140, 141].
Several studies have also demonstrated that specific protein kinases could differentially modulate Oat1 and 3 transports of organic anions.
As mentioned earlier, renal Oat1 and 3 were influenced by certain pathological status and strongly correlated with the progression of diabetic kidney diseases [16] and para-aminohippurate (PAH) is a prototypical substrate for rOat1 and 3 transporters that are mainly localized on the basolateral membrane of renal proximal tubules [8, 9, 11].
One change from the ITC white paper is that all investigational drugs should be evaluated as inhibitors of the renal uptake transporters OCT2, OAT1, OATS, without regard to likely co-medications; the white paper recommended evaluating new drugs as inhibitors of one of these transporters if they were likely to be co-administered with a substrate of the same transporter.
(2007) Downregulation of organic anion transporters OAT1 and OAT3 correlates with impaired secretion of para-aminohippurate after ischemic acute renal failure in rats.
Torres, "Time course of organic anion excretion in rats with bilateral ureteral obstruction: role of organic anion transporters (Oat1 and Oat3)," Nephron Physiology, vol.
Torres, "Renal expression and function of Oat1 and Oat3 in rats with vascular calcification," Pharmacology, vol.
For rat kidneys, androgen-dependent expression of Oat1, Oat3, and Oct2 and higher expression of Oat2 in females was reported, suggesting sex-dependent renal drug handling at least in this species [12, 13].
Lithospermic acid, rosmarinic acid, salvianolic acid A, salvianolic acid B, and protocatechuic acid were reported to have inhibitory effects towards human organic anion transporter 1 (OAT1) and OAT3 with Kt values of 20.8 and 0.59, 0.35 and 0.55,5.6 and 0.16,22.2 and 19.8, and 13.4 and 81.8 [micro]M, respectively [54, 55].
Rat renal cortical OAT1 and OAT3 exhibit gender differences determined by both androgen stimulation and estrogen inhibition.