Renal Secretion of Hydrochlorothiazide Involves Organic Anion Transporter 1/3, Organic Cation Transporter 2, and Multidrug and Toxin Extrusion Protein 2-K.

Renal Secretion of Hydrochlorothiazide Involves Organic Anion Transporter 1/3, Organic Cation Transporter 2, and Multidrug and Toxin Extrusion Protein 2-K. Am J Physiol Renal Physiol. 2019 Jul 19;: Authors: Yin J, Wagner DJ, Prasad B, Isoherranen N, Thummel KE, Wang J Abstract Hydrochlorothiazide (HCTZ) is the most widely used thiazide diuretic for the treatment of hypertension either alone or in combination with other antihypertensives. HCTZ is mainly cleared by the kidney via tubular secretion but the underlying molecular mechanisms are unclear. Using cells stably expressing major renal organic anion and cation transporters (hOAT1, hOAT3, hOCT2, hMATE1, and hMATE2-K), we found that HCTZ interacted with both organic cation and anion transporters. Uptake studies further showed that HCTZ is transported by hOAT1, hOAT3, hOCT2, and hMATE2-K, but not by hMATE1. Detailed kinetic analysis coupled with quantification of membrane transporter proteins by targeted proteomics revealed that HCTZ is an excellent substrate for hOAT1 and hOAT3. The apparent affinities (Km) for hOAT1 and hOAT3 are 112 ± 8 and 134 ± 13 μM, respectively; and the calculated turnover numbers (kcat) are 2.48 and 0.79 s-1, respectively. On the other hand, hOCT2 and hMATE2-K showed much lower affinity for HCTZ. The calculated transport efficiency (kcat/Km) at the single transporter level follows the rank order of hOAT1> hOAT3> hOCT2 and hMATE2-K, suggesting a major role ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
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Source: Nuclear Medicine Communications - Category: Nuclear Medicine Tags: Original Articles Source Type: research
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