Table 1.
Summary of renal β2AR activity in the literature
| No. | Cited Reference | Renal Condition/Study Model | β2AR Activity |
|---|---|---|---|
| 1 | Vandongen et al. (11) | Effects of β-AR modulation on renin secretion in isolated perfused rat kidney | Increased renin secretion |
| 2 | Grospietsch et al. (12) | Changes in hormones and salt handing following long-term infusion of β2-agonist fenoterol and calcium channel blocker verapamil in pregnant rabbits | Increased plasma renin and antidiuretic hormone, and reduced plasma aldosterone, urinary sodium, potassium excretion, and clearance of creatinine |
| 3 | Grospietsch et al. (13) | Changes in urine and electrolyte balance following a bolus injection of β2-agonist fenoterol in female rabbits | β2-Agonism had antidiuretic effect, increased urinary osmolarity, and reduced sodium, potassium, and urine excretion |
| 4 | Singh et al. (14) | Effects of β2 blocker ICI-118551 on tubular function in cultured rat proximal tubule epithelial cells | Increased the activity of Na-K-ATPase and apical sodium entry independent of the cAMP and β2-antagonism decreased it |
| 5 | Singh et al. (15) | The role of protein kinase C (PKC) in β2AR-induced Na+/K+-ATPase activity and sodium transport in cultured rat proximal tubule cells | PKC mediated the β2AR-induced activity of Na-K-ATPase and apical sodium entry |
| 6 | Nakamura et al. (16) | Dose-response study of β2-agonist terbutaline on lipopolysaccharide (LPS)-induced IL-6 production in primary rat renal macrophage cells | β2-Agonism decreased LPS-induced IL-6 production at low concentration via an independent-cAMP suppression of TNF-α and MAPK and increased it at high concentration via a PKA-cAMP pathway |
| 7 | Nakamura et al. (17) | Effects of terbutaline, a β2-AR agonist, on Shiga toxin (Stx)2-induced apoptosis in adenocarcinoma-derived (ACHN) cells, as a model of human renal tubular epithelial cells | β2-Agonism dose-dependently inhibited Shiga toxin (Stx)2-induced apoptosis through cAMP-PKA pathway and p38MAPK cascade |
| 8 | Nakamura et al. (18, 19) | The role of β2-ARs in a rat model of endotoxin-induced acute renal failure | Adenoviral delivery of β2-ARs increased GFR and sodium reabsorption |
| 9 | Nakamura et al. (20) | To determine the role of β2-AR in renal pathophysiology in Wistar rats over-expressing renal β2-AR and by analyzing intrarenal β2-AR expression in 34 children and the changes in serum creatinine levels of 99 children who received beta2-AR agonists | Treatment with terbutaline in rats overexpressing renal β2AR reduced glomerular function and systemic blood pressure to a greater extent and was associated with higher mortality. Clinically, renal β2AR expression slowly increases with age and was upregulated by steroid therapy and may increase the risk of renal side effects in children receiving β2-agonists. |
| 10 | Nakamura et al. (21) | The role of β2-inhibitor ICI118,551 in pathology of LPS-induced septic rats | The combination of LPS and the β2-antagonist increased renal TNFα, CD14, TLR4 and decreased Gsα and cAMP. |
| 11 | Nakamura et al. (22) | The effect of kidney-specific β2-AR gene delivery on kidney function in endotoxemic rat model of acute renal failure (ARF) induced by renal artery occlusion and subcutaneous injections of Escherichia coli | Renal-specific overexpression of β2-AR improved renal dysfunction and declined the reduction rate of creatinine clearance and decreased expression levels of cannabinoid-1 (CB-1) receptor, CD14, TLR4, and TNF-α protein in the kidney |
| 12 | Chen et al. (23) | Effect of β2-AR gene variants on glomerular filtration rate (GFR) decline rate in 580 African-American participants with progressive hypertensive nephropathy | Gly16Arg gene variant in haplotype-3 significantly correlated with the risk of end-stage renal disease |
| 13 | Mu et al. (24) | The role of β2-AR signaling on the pathology of salt-sensitive rat model of hypertension | β2-AR activation leads to Na+ retention and finally salt-dependent hypertension via downregulation of WNK4 |
| 14 | Wills et al. (25) | Effects of β-agonists on mitochondrial biogenesis in primary renal proximal tubule cells (RPTC) isolated from female New Zealand white rabbits and primary adult feline cardiomyocytes (AFC) | β2-AR activation increased mitochondrial function in both cell lines |
| 15 | Wills et al. (25) | The in vivo changes of mitochondrial function following daily intraperitoneal injections of formoterol for 1 or 3 days | β2-AR agonism induced mitochondrial biogenesis, elevation in mtDNA copy number, and transcription of genes associated with mitochondrial electron transport chain in renal and cardiac tissues |
| 16 | Jesinkey et al. (26) | Effect of formoterol, on mitochondrial biogenesis and restoration of renal function in rats with ischemia-reperfusion induced acute kidney injury | β2-AR activation caused a rapid recovery of serum creatinine levels. It also reduced kidney injury molecule (KIM-1) levels and improved histological appearance and mitochondrial function |
| 17 | Li et al. (27) | The mechanism of cAMP-mediated protection in adriamycin (ADR) and puromycin aminonucleoside (PAN)-induced podocyte injury model | cAMP protected against PAN-induced podocyte loss via PKA. PKA signaling protected podocytes by inducing mitochondrial fusion. In vivo forskolin improved ADR-induced proteinuria and podocyte injury. |
| 18 | Wang et al. (28) | The role autoantibodies against β1, β2, and α1-AR in incidence of chronic cardiorenal syndrome (CRS) in 98 participants including 30 chronic cardiorenal syndrome CRS patients, 30 heart failure patients without kidney disease, and 38 healthy individuals | There is a strong correlation between the titer of auto-antibodies against β1, β2, and α1-AR and incidence of chronic cardiorenal syndrome (CRS) |
| 19 | Fujiu et al. (29) | The role of β2ARs in heart-brain-kidney interactions in response to pressure overload in a mouse model of transaortic constriction-induced heart failure | β2ARs in collecting duct cells are central to a proper hypertrophic response to pressure overload |
| 20 | Noh et al. (30) | Effects of β2AR agonists on TNF-α production in vitro (in phorbol myristate acetate-induced rat bone marrow macrophages and PBMCs isolated from streptozotocin-induced diabetic rats) and on diabetic nephropathy in vivo in Zucker diabetic fatty rats | β2-Agonism decreased TNF-a production in vitro and reduced monocyte activation, proinflammatory, and profibrotic responses in the kidneys in vivo |
| 21 | Cameron et al. (31) | Induction of mitochondrial biogenesis by formoterol | Unique structural features of formoterol allow it to interact with the β2-AR to activate the Gβγ-Akt-eNOS-sGC pathway to induce mitochondrial biogenesis |
| 22 | Stallaert et al. (32) | The influence of β2-AR on intracellular Ca2+ in HEK293S cells | Increased intracellular Ca2+ via activation of a IP3-dependent pathway through stimulating Gq-coupled P2Y purinergic receptors |
| 23 | Arif et al. (33) | The impact of formoterol, a long-acting β2-AR agonist on restoration of glomerular filtration in injured podocytes in acute nephrotoxic serum nephritis and chronic adriamycin glomerulopathy mouse models | Formoterol restored glomerular filtration via improving mitochondrial biogenesis in injured podocytes |
| 24 | Cameron et al. (34) | Investigating the cell type responsible for formoterol-induced recovery of renal function in mice after ischemia-reperfusion (IR) injury as a model of acute kidney injury (AKI) using mice with proximal tubule-specific knockout of the β2AR | Renal proximal tubule cells are required for formoterol-mediated protection against AKI |
| 25 | Ha et al. (35) | The prognostic value of β2AR gene (ADRB2) in patients with clear cell renal cell carcinoma (ccRCC) | Reduced ADRB2 expression is associated with poor prognosis in ccRCC patients |
| 26 | Zicha et al. (36) | Disputing the role of renal β2-adrenergic-WNK4-NCC pathway important in salt hypertension of Dahl rats | Propanolol failed to reduce hypertension in salt-sensitive rat suggesting no essential role for a renal βAR-WNK4-NCC pathway in pathogenesis and/or maintenance of salt hypertension in Dahl rats |
| 27 | Frame et al. (37) | β2-AR involvement in the sympathetic regulation of NCC in norepinephrine-evoked salt-sensitive hypertension in Sprague–Dawley rats | Norepinephrine-evoked hypertension is mostly mediated via β-adrenoceptor activation independently of the regulation of NCC. |
| 28 | Bhargava et al. (38) | The mechanism of formoterol-induced mitochondrial biogenesis in renal proximal tubule cells (RPTCs) isolated from female New Zealand White rabbit kidneys | β2AR agonist increased mitochondrial biogenesis (MB) through sGC/cGMP/PKG/p38/PGC-1 pathway |
| 29 | Cleveland et al. (39) | The role of formoterol on renal cortical mitochondrial function and energy production in diabetic db/db mice and in renal proximal tubule cells treated with high glucose | Formoterol restored expression of electron transport chain proteins in complexes I, II, III, and V and increased ATP levels in the renal cortex which were impaired in untreated db/db mice and glucose-exposed RPTC. |
β2AR, β2 adrenergic receptors; cAMP, adenosine 3′,5′-cyclic monophosphate; CD, collecting duct; eNOS, endothelial nitric oxide synthase; GFR, glomerular filtration rate; IL-6, interleukin-6; MAPK, mitogen-activated protein kinase; NCC, sodium chloride cotransporter; PKA, protein kinase A; sGC, soluble guanylyl cyclase; TLR4, Toll-like receptor 4; TNF-α, tumor necrosis factor α; WNK4, with-no-lysine (K) kinase 4.