Immunohistochemical Localization of<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:msub><mml:mrow><mml:mtext mathvariant="bold">AT</mml:mtext></mml:mrow><mml:mrow><mml:mtext mathvariant="bold">1a</mml:mtext></mml:mrow></mml:msub></mml:mrow></mml:math>,<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:msub><mml:mrow><mml:mtext mathvariant="bold">AT</mml:mtext></mml:mrow><mml:mrow><mml:mtext mathvariant="bold">1b</mml:mtext></mml:mrow></mml:msub><

Premer, Courtney; Lamondin, Courtney; Mitzey, Ann M.; Speth, Robert C.; Brownfield, Mark S.

doi:10.1155/2013/175428

Cited by 42 publications

(37 citation statements)

References 180 publications

(219 reference statements)

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“…However, we cannot explain why the 44-kDa band detected by Sc1473 in murine heart disappeared in knockout animals when studied by Bundgaard et al (2010) but not by us. Of note, in line with our findings, it has recently been discussed whether the lack of disappearance of staining with antibodies directed against the C-terminus of the AT 1a angiotensin II receptor in corresponding knockout mice may represent false negative data because that disruption also did not eliminate the C-terminus (Premer et al 2013). Thus, knockout approaches causing functional inactivation of a receptor but not eliminating expression of its C-terminus may be an inappropriate approach for the testing of antibodies raised against this part of the receptor.…”

Section: Discussionsupporting

confidence: 88%

Rat β3-adrenoceptor protein expression: antibody validation and distribution in rat gastrointestinal and urogenital tissues

Cernecka

Pradidarcheep

Lamers

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

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β3-Adrenoceptors play important roles in the regulation of urogenital and probably gastrointestinal function. However, despite recent progress, their detection at the protein level has remained difficult due to a lack of sufficiently validated selective antibodies. Therefore, we have explored the selectivity of two antibodies for the detection of rodent β3-adrenoceptors in immunoblots and immunohistochemistry. Of two reportedly promising candidates, antibody AB15688 did not exhibit subtype selectivity in immunoblots. In contrast, the antibody Sc1473 exhibited at least some selectivity in immunoblots and more promising results in immunocytochemical and immunohistochemical stains in cells transfected with cloned β-adrenoceptor subtypes and in rat and mouse tissues. In a systematic screening of rat gastrointestinal and urogenital tissues, Sc1473 produced selective staining in the epithelial cell lining of the stomach and the urothelium of ureter and bladder. We conclude that the two tested antibodies are inappropriate or at least insufficient for immunoblotting applications, but Sc1473 appears to be useful for immunohistochemical detection of β3-adrenoceptor protein in rodent tissues. The β3-adrenoceptor protein exhibits a distinct expression pattern in the rat gastrointestinal and urogenital tract, which is at least partly in line with previously reported functional data.

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Section: Discussionsupporting

confidence: 88%

Rat β3-adrenoceptor protein expression: antibody validation and distribution in rat gastrointestinal and urogenital tissues

Cernecka

Pradidarcheep

Lamers

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

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“…In addition to AT 1a Rs, ANG II can also activate brain AT 1b Rs. However, whether AT 1b Rs are present in the PVN is controversial, with studies supporting (14,58) or arguing against (30,39) its presence within the PVN. Since both AT 1 R subtypes share similar intracellular signaling pathways, we cannot rule out at present a possible role for AT 1b Rs in ANG II-mediated ROS production in the PVN.…”

Section: Tlr4 In Microglia Is Involved In Ang Ii-mediated Ros Within mentioning

confidence: 99%

Cross talk between AT₁receptors and Toll-like receptor 4 in microglia contributes to angiotensin II-derived ROS production in the hypothalamic paraventricular nucleus

Biancardi

Stranahan

Krause

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

109

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II is thought to increase sympathetic outflow by increasing oxidative stress and promoting local inflammation in the paraventricular nucleus (PVN) of the hypothalamus. However, the relative contributions of inflammation and oxidative stress to sympathetic drive remain poorly understood, and the underlying cellular and molecular targets have yet to be examined. ANG II has been shown to enhance Toll-like receptor (TLR)4-mediated signaling on microglia. Thus, in the present study, we aimed to determine whether ANG II-mediated activation of microglial TLR4 signaling is a key molecular target initiating local oxidative stress in the PVN. We found TLR4 and ANG II type 1 (AT 1) receptor mRNA expression in hypothalamic microglia, providing molecular evidence for the potential interaction between these two receptors. In hypothalamic slices, ANG II induced microglial activation within the PVN (ϳ65% increase, P Ͻ 0.001), an effect that was blunted in the absence of functional TLR4. ANG II increased ROS production, as indicated by dihydroethidium fluorescence, within the PVN of rats and mice (P Ͻ 0.0001 in both cases), effects that were also dependent on the presence of functional TLR4. The microglial inhibitor minocycline attenuated ANG II-mediated ROS production, yet ANG II effects persisted in PVN single-minded 1-AT 1a knockout mice, supporting the contribution of a non-neuronal source (likely microglia) to ANG II-driven ROS production in the PVN. Taken together, these results support functional interactions between AT 1 receptors and TLR4 in mediating ANG II-dependent microglial activation and oxidative stress within the PVN. More broadly, our results support a functional interaction between the central renin-angiotensin system and innate immunity in the regulation of neurohumoral outflows from the PVN. ANGIOTENSIN II (ANG II) plays a critical role in fluid balance and hemodynamic regulation (25). Within the central nervous system (CNS), ANG II acting through ANG II type 1 a (AT 1a ) receptors (AT 1a R) has been shown to be implicated in the regulation of sympathetic and neuroendocrine outputs from the brain (45, 49, 50). The paraventricular nucleus (PVN) of the hypothalamus has been recognized as a critical neuronal substrate mediating central ANG II actions, thus playing a critical role in ANG II-mediated neurohumoral responses (23, 78). Indeed, a large body of evidence supports enhanced angiotensinergic actions within the CNS, including the PVN, as a key pathophysiological mechanism involved in cardiovascular diseases, including hypertension and heart failure (37,60,78,80,88). However, despite its importance, the precise mechanisms and cellular/ molecular targets underlying ANG II signaling within the CNS are incompletely understood.Inflammation and oxidative stress have emerged as novel mechanisms by which central ANG II mediates its deleterious effects. For example, studies have shown that pressor and sympathetic responses to central ANG II are mediated by superoxide within the PVN (8, 22). Likewise, several studie...

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“…Apart from their role in cardiovascular regulation, RAS components within the central nervous system have other functions mediated by AT 1 and/or AT 2 receptors (Paul et al, 2006;Premer et al, 2013;Wright and Harding, 2011). In particular, previous studies have demonstrated that several neuromodulators, including angiotensin II acting on AT 1 receptors, are involved in cardiovascular regulation within the NTS (Arnold et al, 2010;Cheng et al, 2010Cheng et al, , 2012Kasparov et al, 1998;Mosqueda-Garcia et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

“…In particular, previous studies have demonstrated that several neuromodulators, including angiotensin II acting on AT 1 receptors, are involved in cardiovascular regulation within the NTS (Arnold et al, 2010;Cheng et al, 2010Cheng et al, , 2012Kasparov et al, 1998;Mosqueda-Garcia et al, 1990). Accordingly, high levels of ACE (Rogerson et al, 1995) and high densities of AT 1 receptors have been found at the level of the NTS in the rabbit (Aldred et al, 1993) as well as in many other mammals including humans (Paul et al, 2006;Premer et al, 2013;Wright and Harding, 2011). …”

Section: Introductionmentioning

confidence: 99%

The cough reflex is upregulated by lisinopril microinjected into the caudal nucleus tractus solitarii of the rabbit

Cinelli

Bongianni

Pantaleo

et al. 2015

Respiratory Physiology & Neurobiology

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a b s t r a c tWe have previously shown that cough potentiation induced by intravenous administration of the AT 1 receptor antagonist losartan is lower than that induced by the ACE inhibitor lisinopril in anesthetized and awake rabbits. Since losartan and lisinopril cross the blood-brain barrier, their central action on the cough reflex can be hypothesized. Mechanical stimulation of the tracheobronchial tree and citric acid inhalation were used to induce cough reflex responses in pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bilateral microinjections (30-50 nl) of losartan (5 mM), lisinopril (1 mM), bradykinin (0.05 mM), HOE-140 (0.2 mM, a bradykinin B 2 receptor antagonist) and CP-99,994 (1 mM, an NK 1 receptor antagonist) were performed into the caudal nucleus tractus solitarii, the predominant site of termination of cough-related afferents. Lisinopril, but not losartan increased the cough number. This effect was reverted by HOE-140 or CP-99,994. Cough potentiation was also induced by bradykinin. The results support for the first time a central protussive action of lisinopril mediated by an accumulation of bradykinin and substance P.

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Immunohistochemical Localization ofAT1a,AT1b<

Cited by 42 publications

References 180 publications

Rat β3-adrenoceptor protein expression: antibody validation and distribution in rat gastrointestinal and urogenital tissues

Rat β3-adrenoceptor protein expression: antibody validation and distribution in rat gastrointestinal and urogenital tissues

Cross talk between AT₁receptors and Toll-like receptor 4 in microglia contributes to angiotensin II-derived ROS production in the hypothalamic paraventricular nucleus

The cough reflex is upregulated by lisinopril microinjected into the caudal nucleus tractus solitarii of the rabbit

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Immunohistochemical Localization ofAT1a,AT1b<

Cited by 42 publications

References 180 publications

Rat β3-adrenoceptor protein expression: antibody validation and distribution in rat gastrointestinal and urogenital tissues

Rat β3-adrenoceptor protein expression: antibody validation and distribution in rat gastrointestinal and urogenital tissues

Cross talk between AT1receptors and Toll-like receptor 4 in microglia contributes to angiotensin II-derived ROS production in the hypothalamic paraventricular nucleus

The cough reflex is upregulated by lisinopril microinjected into the caudal nucleus tractus solitarii of the rabbit

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Cross talk between AT₁receptors and Toll-like receptor 4 in microglia contributes to angiotensin II-derived ROS production in the hypothalamic paraventricular nucleus