Localization of angiotensin II type 1 receptor subtype mRNA in rat kidney

Abstract

The physiological effects of angiotensin II (ANG II) on the kidney are mediated primarily by the ANG II type 1 (AT1) receptor. Two highly similar AT1 receptor subtypes have been identified in the rat by molecular cloning techniques, namely AT1A and AT1B. The intrarenal localization of the AT1A and AT1B receptor subtypes has not been studied by hybridization methods with subtype-specific receptor probes. Using radiolabeled probes from the 3' noncoding region of the AT1A and AT1B cDNAs, we localized AT1 mRNA in rat kidney by in situ hybridization. Specificity of the 3' noncoding region probes was tested by Northern blot and solution hybridization methods. AT1A mRNA levels were highest in the liver, kidney, and adrenal. In contrast, AT1B mRNA levels were highest in the adrenal and pituitary and low in kidney. Autoradiographic localization of 125I-[Sar1,Ile8]ANG II binding indicated that the highest levels of AT1 receptors were found in glomeruli and vascular elements. In situ hybridization with a nonselective AT1 receptor riboprobe indicated that the highest levels of AT1 mRNA were in the outer medullary vasa recta and cortical glomeruli with additional diffuse labeling of the cortex and outer medulla, consistent with labeling of tubular elements. In contrast, in situ hybridization with the AT1 subtype selective probes revealed that AT1A receptor mRNA was primarily localized to the vasa recta and diffusely to the outer stripe of the outer medulla and the renal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization and Functional Properties of Angiotensin II AT1 Receptors in the Kidney. Focus on Renomedullary Interstitial Cells.

“…While localization of mRNAs for Ang II receptor subtypes in the kidney by reverse transcription polymerase chain reaction (RT-PCR) or in situ hybridization agrees generally with the results of most receptor mapping studies (29,(51)(52)(53), the distribution of AT1 receptor mRNA is more widespread (65)(66)(67)(68). For example, in addition to the well described AT1 receptor binding sites in the glomeruli, outer cortex, and inner stripe of the outer medulla, an early study using RT-PCR with a rat AT1A specific oligonucleotide primer pair detected AT1A mRNA in the rat renal papilla (65).…”

“…For example, in addition to the well described AT1 receptor binding sites in the glomeruli, outer cortex, and inner stripe of the outer medulla, an early study using RT-PCR with a rat AT1A specific oligonucleotide primer pair detected AT1A mRNA in the rat renal papilla (65). Subsequent in situ hybridization studies demonstrated AT1A receptor mRNA labelling in the outer stripe of the outer medulla (66) or AT1B mRNA expression in the tip of the papilla (68). These observations are surprising given that little AT1 receptor binding has been demonstrated in the outer stripe of the outer Red indicates the highest density of binding, whereas blue shows the background level.…”

AT2‐antagonist sensitive potentiation of angiotensin II‐induced vasoconstrictions by blockade of nitric oxide synthesis in rat renal vasculature

“…Although AT 2 -R have been detected in large vessels of various species (for reviews see Navar et al, 1996;Zhuo et al, 1996), AT 1 -R are the dominant subtype in the adult kidney vasculature and all of the major actions of Ang II on renal hemodynamics appear to be mediated primarily by activation of the AT 1 -R subtype (Navar et al, 1996). Moreover, among the two isoforms of the AT 1 -R, AT 1A and AT 1B , AT 1A is the predominant isoform in the kidney (Gasc et al, 1994;Healy et al, 1995). The hypothesis that AT 2 -R antagonists aect renal haemodynamics remains elusive.…”

Activation of Endothelin-A Receptors Contributes to Angiotensin-Induced Suppression of Renal Sensory Nerve Activation

“…28 -30 Although there is currently little evidence for ETA-R in the renal pelvic wall, AT1-Rs have been localized to the renal pelvic wall. 31 Also, we have demonstrated the presence of both Ang II and ET-1 in the renal pelvic wall. 10,16 Because of the demonstrated interaction between Ang II and ET-1 in the cardiovascular system 20,22,24 -27 and the similar enhancements produced by the AT1-R and ETA-R antagonists of the responsiveness of renal mechanosensory nerves in rats on low-sodium diet, 9,16 we hypothesized that activation of ETA-R contributes to the Ang II-induced suppression of the renorenal reflexes.…”

“…[1][2][3] Importantly, AT1-R has been located in the renal pelvic wall. 31 Although there is currently little information on the location of ETA-R in the renal pelvic wall, the presence of ETA-R in vascular smooth muscle layers throughout the kidney 35 suggests that these receptors are also found in the renal pelvic wall.…”