Receptor-Mediated Effects of Angiotensin II on Neurons

doi:10.1006/frne.1994.1009

Frontiers in Neuroendocrinology

Volume 15, Issue 3, September 1994, Pages 203-230

https://doi.org/10.1006/frne.1994.1009 Get rights and content

Abstract

Aside from its well-known and numerous actions at peripheral tissues, the octapeptide angiotensin II (ANG II) elicits specific receptor-mediated effects within the central nervous system. In this review we focus on the receptor-mediated actions of ANG II on neurons. The distribution of ANG II receptors in the brain and physiological, electrophysiological, and cellular effects mediated by these receptors are discussed. This is extended to a review of the characteristics of ANG II receptor subtypes on cultured neurons and the cellular and genomic actions mediated by these receptors. Finally, we develop this information into speculative models for the cellular effects mediated by each ANG II receptor subtype in neurons.

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Cited by (75)

Angiotensin-(1-7) enhances LTP in the hippocampus through the G-protein-coupled receptor Mas
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The renin–angiotensin system not only plays a critical role in blood pressure control but is also involved in learning and memory mechanisms. In addition to angiotensin (Ang) II, Ang-(1–7) may also have important biological activities in the brain. Here, we show for the first time that Ang-(1–7) enhances long-term potentiation (LTP) in the CA1 region of the hippocampus. Our studies with AT1 receptor antagonists and selective Ang-(1–7) receptor antagonists demonstrate the existence of a distinct Ang-(1–7) receptor in the brain, the G-protein-coupled receptor Mas, encoded by the Mas protooncogene. We also show that the genetic deletion of this receptor abolishes the Ang-(1–7)-induced enhancement of LTP. Thus, we firstly demonstrate that Ang-(1–7) influences the induction of LTP in limbic structures implicating its distinct function in learning and memory mechanisms; secondly, we have identified Mas as a functional receptor for Ang-(1–7) in the brain.
Modulation of delayed rectifier potassium current by angiotensin II in CATH.a cells
2003, Biochemical and Biophysical Research Communications
Citation Excerpt :
In addition, it is necessary to understand the specific involvement of PKC and CaMKII in the Ang II-induced increase in NE release. In summary, it is established that some of the physiological actions of Ang II in the brain involve modulation of central noradrenergic neurons [25,26]. In this study, we have characterized catecholaminergic CATH.a cells in terms of Ang II receptors and AT1 receptor-mediated electrophysiological responses, and believe that these cells may provide an excellent model system for analysis of Ang II effects on NE at the single cell level.
Angiotensin II (Ang II) modulates, via Ang II type 1 (AT₁) receptors, the activity of brain catecholaminergic neurons. Here we utilized catecholaminergic CATH.a cells to define the effects of Ang II on delayed rectifier K⁺ current (I_Kv), one of the factors that determines changes in neuronal activation. Receptor binding analyses demonstrated the presence of AT₁ receptors in CATH.a cells. Whole cell voltage clamp experiments in these cells revealed that Ang II (100 nM) produced a significant inhibition of I_Kv, that was abolished by the AT₁ receptor blocker, losartan (1 μM), or by inhibition of phospholipase C (PLC) with U73122 (10 μM). Furthermore, this action of Ang II was completely abolished by co-inhibition of protein kinase C (PKC) and calcium/calmodulin protein kinase II (CaMKII). These results demonstrate that Ang II produces an inhibition of I_Kv in CATH.a cells, via an intracellular pathway that includes PLC, PKC, and CaMKII.
Angiotensin II-induced ionic currents and signalling pathways in submandibular ganglion neurons
2003, Archives of Oral Biology
Citation Excerpt :
Since CaM K II is activated by physiological elevations in [Ca2+]i,51,52 stimulation of receptors linked to PLC may cause activation of both PKC and CaM K II. There are some evidences that Ang II increases in PLC-mediated phosphoinositide (PI) hydrolysis, followed by increases in PKC activity and [Ca2+]i.50,53 There is also evidence that CaM K II is an essential signalling pathways of Ang II in vascular smooth muscle cells.54 In other neurons, there is also evidence that AT1 receptors activates mitogen-activated protein (MAP) kinase.55,56
Angiotensin II (Ang II) is one of the most important vasoconstrictive hormones but is also known to act as a neuromodulator and a neurotransmitter in the central and peripheral nervous system. The submandibular ganglion (SMG) neuron is a parasympathetic ganglion which receives inputs from preganglionic cholinergic neurons, and innervates the submandibular salivary gland to control saliva secretion. In this study, the effects of Ang II on SMG neurons were investigated using the whole-cell patch clamp technique. Membrane currents evoked by a ramp pulse from +50 to −100 mV (−150 mV/500 ms) were compared in both the absence and presence of Ang II. In eight neurons tested, 1 μM Ang II increased inward currents by 42.0±8.2%. The reversal potentials of the Ang II-induced current were 0.2±0.6 mV. These increase of inward currents by Ang II were antagonized by losartan, a selective antagonist of AT₁ receptors. Intracellular dialysis with 0.1 mM guanosin 5′-O-(2-thiodiphosphate) (GDP-β-S), a G-proteins blocker, and anti-G_q/11 antibody attenuated Ang II-induced ionic current. In addition, pretreatment of neurons with 10 μM staurosporine (stauro), a protein kinase C (PKC) inhibitor, 0.5 μM PMA, a PKC activator, and 10 μM KN-93, a Ca²⁺/calmodulin-dependent protein kinase II (CaM K II) inhibitor, attenuated Ang II-induced ionic current in SMG neurons. The data presented here demonstrated that Ang II-induced ionic current via G_q/11-proteins involving both PKC and CaM K II pathways in SMG neurons.
Cerebrospinal fluid angiotensin-converting enzyme (ACE) correlates with length of illness in schizophrenia
2000, Schizophrenia Research
The aim of the study was to evaluate a possible progression with time of cerebrospinal fluid (CSF) angiotensin-converting enzyme (ACE) levels in treated schizophrenia patients. CSF ACE was determined in duplicate by a sensitive inhibitor-binding assay (IBA) from morning CSF samples of 56 acute and chronic in-patients with schizophrenic psychoses diagnosed according to DSM-IV. CSF ACE correlated significantly with length of schizophrenic psychosis (r=0.39, p=0.003). There was also a positive significant correlation between CSF ACE and duration of current psychotic episode (r=0.39, p=0.003) as well as duration of current hospitalization (r=0.66, p<0.001). These significances were maintained even when patients who were not treated with antipsychotics at the time of sampling were excluded. The correlations also remained significant when controlling for current neuroleptic dose in chlorpromazine equivalents. Serum ACE did not correlate with any clinical variable. No significant correlations between serum or CSF ACE and age, diagnostic subgroup, gender, serum ACE, CSF to serum albumin ratios, or neuroleptic dose in chlorpromazine equivalents were detected. The elevation of CSF ACE seemed to be confined to a subgroup of chronic patients with few positive symptoms. Elevated CSF ACE may reflect an increased solubilization of ACE from cell membranes in the central nervous system or constitute an increased expression of the ACE gene in response to some stimuli. This may be a function of treatment or a result of the deteriorating schizophrenic process.
Transgenic and knockout models in renin-angiotensin system
1999, Immunopharmacology
The renin–angiotensin system, composed of enzymatic and signal-transduction cascades, plays a key role in the regulation of arterial blood pressure and in the development of certain forms of experimental and human hypertension. The products of this system, angiotensin peptides, exert a wide range of physiologically important effects on many tissues, including those of the cardiovascular systems, through their actions on angiotensin receptors. Molecular genetic and transgenic studies have begun to implicate some of the genes encoding components of the renin–angiotensin system in the development of cardiovascular diseases. Recently, we succeeded in generating transgenic mice with chronic hypertension and with inducible hypertension during pregnancy and in creating mice homozygous for a targeted disruption of the angiotensinogen gene (the only known precursor of angiotensins), resulting in the complete loss of angiotensin signals in vivo. Here, we will review recent advances related to the functional analysis of the renin–angiotensin system, in particular by focusing on transgenic approaches including gene targeting.
Phasic bursting activity of paraventricular neurons is modulated by temperature and angiotensin II
1999, Journal of Thermal Biology
- 1.
  Impulse activity of phasically firing (bursting) paraventricular neurons, which are assumed to be of the vasopressinergic type, have been extracellularly recorded in brain slices of the rat.
- 2.
  Analysis of burst patterns during temperature changes, angiotensin II application and combined application of both stimuli demonstrated that certain burst parameters are effected much stronger than the mean firing rate and also for a longer period of time.
- 3.
  The most sensitive parameter was the intraburst frequency which is considered to be the most effective parameter for increased vasopressin release.
- 4.
  These data indicate that there are functionally relevant changes in the impulse patterns which are not necessarily manifested in the mean firing rate.

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Regular ArticleReceptor-Mediated Effects of Angiotensin II on Neurons

Abstract

Regular Article
Receptor-Mediated Effects of Angiotensin II on Neurons