Expression of sulphonylurea receptor protein in mouse kidney

Abstract

The sulphonylurea receptor (SUR) is the site of action for sulphonylurea derivatives such as glibenclamide, which are widely used as oral hypoglycaemic agents. Sulphonylureas have also been shown to affect urine flow and salt excretion by the kidney; therefore, the use of these drugs may have important implications for the pharmacological manipulation of renal salt handling. The purpose of the present investigation was to increase our understanding of the possible role of SUR in the regulation of renal function by determining the distribution of SUR isoforms within mouse kidney. Immunostaining with anti-SUR antisera revealed specific staining of SUR2B in distal nephron segments of mouse kidney. A diffuse, low level staining was observed in proximal tubules in the inner cortical region. No evidence was found for the presence of SUR2B in intra-renal blood vessels. Reverse-transcription polymerase chain reaction and Western blotting experiments indicated that SUR2B is the only known isoform expressed. These data demonstrate that SUR2B in mouse kidney is expressed in tubule regions that are critical in determining renal salt excretion.

Localization of the Sulphonylurea Receptor Subunits, SUR2A and SUR2B, in Rat Renal Tubular Epithelium

“…The SUR2 protein was shown to be expressed during development of the rat kidney (Hernandez-Sanchez et al 1997). Although SUR2B has been reported to be a regulatory subunit of the K ATP channels in the rodent kidney (Beesley et al 1999), the present study for the fi rst time shows in immunohistochemistry as well as western blotting that both SUR2A and SUR2B are the regulatory subunits of K ATP channels in the rat kidney, which in accord with a previous fi nding of rabbit kidney in western and northern blottings (Brochiero et al 2002). Since such wide distribution of SUR2A and SUR2B in rat kidney was quite similar to that of Kir6.1 (Zhou et al 2007b), it is suggested that both SUR2A and SUR2B combine with Kir6.1 to form functional K ATP channels in the renal tubular epithelium.…”

Cloning of rabbit Kir6.1, SUR2A, and SUR2B: possible candidates for a renal KATP channel

“…In contrast, the rat kidney homologue of SUR2B was recently isolated and shown to be abundantly expressed in rat proximal tubules (41). Beesley et al (9) found that no protein could be detected with anti-SUR2A antiserum in Western blot studies, and no staining could be observed in the immunohistochemistry at dilution of antisera equivalent to that used with anti-SUR2B. Interestingly, at a lower dilution they found a low level of diffuse staining in proximal tubules, which suggests that a low level of SUR2A could be present in the proximal tubule.…”

“…On the other hand, SUR2B mRNAs are ex-pressed in kidney as well as in all other tissues examined (heart, eye, urinary bladder, skeletal muscle, brain, lung, liver, pancreas, spleen, stomach, small intestine, colon, uterus, ovary, and fat tissue) (23). In kidney, high staining was found with SUR2B antisera in distal nephron segments, whereas low, diffuse staining was found in proximal tubules (9).…”

“…However, it is still unknown whether the Kir6.1 subunit, which develops a channel with a 70-pS conductance in Xenopus oocytes (22), is the one responsible for the 50-pS channel in rabbit PCT. Attempts to determine the nature of the SUR subunits in mice and rats show that SUR1 and SUR2A mRNAs are generally absent in the kidney (9,19,23). On the other hand, SUR2B mRNAs are ex-pressed in kidney as well as in all other tissues examined (heart, eye, urinary bladder, skeletal muscle, brain, lung, liver, pancreas, spleen, stomach, small intestine, colon, uterus, ovary, and fat tissue) (23).…”

Comparison between the effect of glibenclamide and captopril on experimentally induced diabetic nephropathy in rats

“…Sulfonylurea compounds were the first available oral antidiabetic agents, and they remain an important tool for optimal glycemic control. 5 Beesley et al 6 demonstrated the presence of a functional rat mesangial K ATP containing unique receptors for sulfonylureas. However, little is known about their possible functional and metabolic effects, independently of the increased insulin secretion and decrease glycemia induced by these compounds.…”