Angiotensin depolarizes parvocellular neurons in paraventricular nucleus through modulation of putative nonselective cationic and potassium conductances

Latchford, Kevin J.; Ferguson, Alastair V.

doi:10.1152/ajpregu.00549.2004

Cited by 28 publications

(21 citation statements)

References 48 publications

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“…We first validated previous observations that neurons in the rat hypothalamus express AT 1 R and the activation of which causes a membrane depolarization (Cato and Toney, 2005; Latchford and Ferguson, 2005). Ang II (1 mM), when applied to the recording neuron from a micropipette by a puff of nitrogen, evoked a membrane depolarization in 10 of the 27 hypothalamic neurons examined (Fig.…”

Section: Resultssupporting

confidence: 73%

“…Ang II depolarizes neurons in the rat paraventricular nucleus via activation of AT 1 R (Cato and Toney, 2005; Latchford and Ferguson, 2005). To validate the effect of Ang-(1-12) on native AT 1 R, whole cell patch clamp recordings were performed on neurons of rat hypothalamic slices in a manner similar to that described (Cato and Toney, 2005; Latchford and Ferguson, 2005).…”

Section: Resultsmentioning

confidence: 99%

“…To validate the effect of Ang-(1-12) on native AT 1 R, whole cell patch clamp recordings were performed on neurons of rat hypothalamic slices in a manner similar to that described (Cato and Toney, 2005; Latchford and Ferguson, 2005). …”

Section: Resultsmentioning

confidence: 99%

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Angiotensin-[1-12] interacts with angiotensin type I receptors

et al. 2014

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Angiotensin-(1-12) [Ang-(1-12)], a newer member of angiotensin peptides, is proposed to be converted enzymatically to angiotensin I (Ang I) and to angiotensin II (Ang II); the latter being the bioactive peptide. We studied the Ang-(1-12) and Ang II responses in COS-7 cells or CHO cells transfected with 5 μg AT1R by monitoring [Ca2+]i using the Fluo-4. Ang II (1 pM-1μM) and Ang-(1-12) (5 pM-5 μM) increased [Ca2+]i with an EC50 of 0.19 nM and 24 nM in COS-7 cells; and 0.65 nM and 28.7 nM in CHO cells. The AT1R antagonist losartan (1 nM-10 μM) suppressed [Ca2+]i induced by Ang-(1-12) and Ang II. In CHO cells transfected with 5 μg AT2R, Ang II (1 pM-1μM) increased [Ca2+]i, with an EC50 of 9.68 nM; whereas, Ang-(1-12) (5 pM-5 μM) failed to elicit a significant change in [Ca2+]i. In CHO cells transfected with AT1R, Ang-(1-12) stimulated ERK phosphorylation with a potency 300-fold less than that of Ang II. To evaluate the activity of Ang-(1-12) on native AT1R, whole cell patch recordings were made from neurons in the rat hypothalamic slices. Ang II or Ang-(1-12) ejected by pressure from a micropipette elicited a membrane depolarization; the latter was blocked by losartan (10 μM), and not affected by the AT2R antagonist PD 123319 (10 μM), nor by the angiotensin converting enzyme inhibitor captopril (10 μM). Our result shows that Ang-(1-12) may produce its biological activity by acting directly on AT1R, albeit at a concentration higher than that of Ang II.

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Section: Resultssupporting

confidence: 73%

Section: Resultsmentioning

confidence: 99%

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Angiotensin-[1-12] interacts with angiotensin type I receptors

et al. 2014

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“…Interestingly, these studies showed that while ANG specifically inhibited the transient potassium conductance I A (while there were not effects on the delayed rectifier IK) in magnocellular neurons, the depolarizing effects of ANG on these cells were the result of simultaneous actions on a glutamate interneuron as these effects were abolished by glutamate antagonists and blockers of synaptic transmission [25]. In contrast the effects of ANG on parvocellular neuroendocrine cells (putative CRH and TRH) appear to result from combined inhibition of IK and activation of a non selective cationic conductance (NSCC) [26]. These multiple direct effects of ANG on different subpopulations of neurons in the PVN are summarized schematically in Figure 3.…”

Section: Peptidergic Regulation Of Pvn Output Neuronsmentioning

confidence: 96%

The paraventricular nucleus of the hypothalamus – a potential target for integrative treatment of autonomic dysfunction

Ferguson

Latchford

Samson

2008

Expert Opinion on Therapeutic Targets

271

178

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Background-The paraventricular nucleus of the hypothalamus (PVN) has emerged as one of the most important autonomic control centers in the brain, with neurons playing essential roles in controlling stress, metabolism, growth, reproduction, immune, and other more traditional autonomic functions (gastrointestinal, renal and cardiovascular).Objectives-Traditionally the PVN was viewed very much as a nucleus in which afferent inputs from other regions were faithfully translated into changes in single specific outputs whether those were neuroendocrine or autonomic. Here we will present data which suggest that PVN in fact plays significant and essential roles in integrating multiple sources of afferent input and sculpting an integrated autonomic output by concurrently modifying the excitability of multiple output pathways. In addition we will highlight recent work which suggests that dysfunction of such intranuclear integrative circuitry may contribute to the pathology of conditions such as hypertension and congestive heart failure.Conclusions-This review highlights data showing that individual afferent inputs (SFO), signaling molecules (orexins, adiponectin), and interneurons (glutamate/GABA), all have the potential to influence (and thus coordinate) multiple PVN output pathways. We also highlight recent studies showing that modifications in this integrated circuitry may play significant roles in the pathology of diseases such as congestive heart failure and hypertension.

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“…56 It is worth noting that chronically high levels of Ang II regulate membrane potential by altering the expression of potassium channel proteins and potassium currents. [57][58][59] This mechanism may be very important in the setting of various disease states that are characterized by sympathoexcitation, such as CHF and hypertension. Data from the laboratory of Sumners and coworkers 60,61 have confirmed this mechanism.…”

Section: Central Angiotensin II and Sympathetic Outflow In Chfmentioning

confidence: 99%