ANG III induces expression of inducible transcription factors of AP-1 and Krox families in rat brain

2005 ◽  
Vol 289 (3) ◽  
pp. R845-R850 ◽  
Author(s):  
Annegret Blume ◽  
Christian Undeutsch ◽  
Yi Zhao ◽  
Elena Kaschina ◽  
Juraj Culman ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Receptor Antagonist ◽  
Paraventricular Nucleus ◽  
Brain Regions ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Rapid Responses ◽  
The Central Nervous System ◽  
Brain Ventricle ◽  
Different Populations

In addition to rapid responses comprising increases in blood pressure, drinking, and stimulation of natriuresis, ANG II induces the expression of transcription factors (TF) in the central nervous system. The ANG II metabolite ANG III (ANG 2–8) has been demonstrated to exert physiological effects similar to those of ANG II. We aimed to determine 1) whether ANG III induces TF expression in the brain, 2) which ANG II (AT) receptor subtype is involved, and 3) whether the two peptides, ANG II and ANG III, differ in their efficacy to stimulate TF expression. ANG II (100 pmol), ANG III (100 pmol), or vehicle was injected into the lateral brain ventricle of conscious rats alone or in combination with the AT1 receptor antagonist losartan (10 nmol), the AT2 receptor antagonist PD-123319 (5 nmol), or the aminopeptidase inhibitor amastatin (10 nmol). Similar to ANG II, ANG III induced the expression of c-Fos, c-Jun, and Krox-24 in four brain regions, subfornical organ, median preoptic area, paraventricular nucleus, and supraoptic nucleus of the hypothalamus, with the same efficacy. This effect was AT1 receptor mediated. Pretreatment with amastatin reduced the expression of TF in response to ANG II, indicating that this expression is partly mediated by ANG III. Interestingly, the AT2 receptor antagonist PD-123319 alone slightly enhanced the expression of c-Fos, c-Jun, and Krox-24 in different populations of neurons of the paraventricular nucleus. These data indicate that different populations of neurons in the paraventricular nucleus are tonically inhibited by AT2 receptors under physiological conditions.

scholarly journals The role of angiotensin II in the early stages of bovine ovulation

Reproduction ◽  
2007 ◽  
Vol 134 (5) ◽  
pp. 713-719 ◽  
Author(s):  
Rogério Ferreira ◽  
João Francisco Oliveira ◽  
Rafael Fernandes ◽  
José Ferrugem Moraes ◽  
Paulo Bayard Gonçalves
Keyword(s):  
Receptor Antagonist ◽  
Gnrh Agonist ◽  
Saline Solution ◽  
Critical Role ◽  
Renin Angiotensin System ◽  
Ovulation Rate ◽  
Receptor Subtype ◽  
Ang Ii

There is evidence that the renin–angiotensin system plays an important role in ovulation in cattle. Using anin vivomodel, we investigated the role of angiotensin (Ang) II in bovine ovulation by injecting Ang II receptor antagonists into ovulatory follicles. Animals (n= 102) were pre-synchronized and, when the follicles reached 12 mm, they were given the respective treatment and the cows received GnRH agonist (i.m.) to induce ovulation. The ovulation rate was significantly lower when 100μM saralasin (Ang II receptor antagonist) was intrafollicularly injected (14.3%) in comparison with saline solution (83.3%). Based on these results, a second experiment was carried out to determine the timing of Ang II’s critical role in ovulation. Saralasin inhibited ovulation only when applied at 0 and 6 h (16.7 and 42.9% ovulation rate in the 0- and 6-h groups respectively), but not at 12 h (100%) following GnRH agonist treatment. To investigate the subtypes of Ang II receptors implicated in the LH-induced ovulation, losartan (LO; AT1-Ang II receptor antagonist), PD123 319 (AT2-Ang II receptor antagonist), LO+PD123 319, or saline were intrafollicularly injected when the cows were challenged with GnRH agonist. Ovulation was inhibited by PD123 319 and LO+PD123 319 (50.0 and 33.3% on ovulation rate respectively), but not by LO or saline solution (100% ovulation in both groups). From these results, we suggest that Ang II plays a pivotal role in the early mechanism of bovine ovulation via the AT2receptor subtype.

scholarly journals Mechanisms of angiotensin II-induced expression of B2 kinin receptors

2004 ◽  
Vol 286 (3) ◽  
pp. H926-H932 ◽  
Author(s):  
Yan Tan ◽  
Florence N. Hutchison ◽  
Ayad A. Jaffa
Keyword(s):  
Receptor Antagonist ◽  
Mapk Pathway ◽  
Renin Angiotensin System ◽  
Receptor Subtype ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Ang Ii ◽  
Western Blots ◽  
Protein Levels ◽  
Kinin Receptors

Although the primary roles of the kallikreinkinin system and the renin-angiotensin system are quite divergent, they are often intertwined under pathophysiological conditions. We examined the effect of ANG II on regulation of B2 kinin receptors (B2KR) in vascular cells. Vascular smooth muscle cells (VSMC) were treated with ANG II in a concentration (10—9-10—6 M)- and time (0–24 h)-dependent manner, and B2KR protein and mRNA levels were measured by Western blots and PCR, respectively. A threefold increase in B2KR protein levels was observed as early as 6 h, with a peak response at 10—7 M. ANG II (10—7 M) also increased B2KR mRNA levels twofold 4 h after stimulation. Actinomycin D suppressed the increase in B2KR mRNA and protein levels induced by ANG II. To elucidate the receptor subtype involved in mediating this regulation, VSMC were pretreated with losartan (AT1 receptor antagonist) and/or PD-123319 (AT2 receptor antagonist) at 10 μM for 30 min, followed by ANG II (10—7 M) stimulation. Losartan completely blocked the ANG II-induced B2KR increase, whereas PD-123319 had no effect. In addition, expression of B2KR mRNA levels was decreased in AT1A receptor knockout mice. Finally, to determine whether ANG II stimulates B2KR expression via activation of the MAPK pathway, VSMC were pretreated with an inhibitor of p42/p44mapk (PD-98059) and/or an inhibitor of p38mapk (SB-202190), followed by ANG II (10—7 M) for 24 h. Selective inhibition of the p42/p44mapk pathway significantly blocked the ANG II-induced increase in B2KR expression. These findings demonstrate that ANG II regulates expression of B2KR in VSMC and provide a rationale for studying the interaction between ANG II and bradykinin in the pathogenesis of vascular dysfunction.

Antidipsogenic actions of endothelins are exerted via the endothelin-A receptor in the brain

1993 ◽  
Vol 265 (5) ◽  
pp. R1212-R1215 ◽  
Author(s):  
W. K. Samson ◽  
T. C. Murphy
Keyword(s):  
Receptor Subtype ◽  
System Control ◽  
Ang Ii ◽  
Drinking Response ◽  
Endothelin A Receptor ◽  
Electrolyte Homeostasis ◽  
Relevant Role ◽  
The Central Nervous System ◽  
The Brain ◽  
Central Nervous System Control

The receptor subtype mediating the antidipsogenic effects of the endothelins (ETs) was determined in conscious, unrestrained, normally hydrated rats. Intracerebroventricular injection of 6, 12, and 20 ng ET-2 resulted in a significant, dose-related inhibition of water drinking in response to subsequent injection of 100 pmol angiotensin II (ANG II). Pretreatment with 50 or 100 ng ET-B receptor agonist failed to alter the subsequent drinking response to ANG II. Drinking in response to ANG II was significantly accentuated in rats pretreated with 50, 100, and 200 ng of the selective ET-A receptor antagonist BQ-123. These data indicate that the antidipsogenic effects of the ETs are mediated via the ET-A receptor subtype and further suggest that endogenous ET plays a physiologically relevant role in the central nervous system control of fluid and electrolyte homeostasis.

scholarly journals Cardamonin Modulates Neuropathic Pain through the Possible Involvement of Serotonergic 5-HT1A Receptor Pathway in CCI-Induced Neuropathic Pain Mice Model

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3677
Author(s):  
Nur Khalisah Kaswan ◽  
Noor Aishah Mohammed Idzham ◽  
Tengku Azam Shah Tengku Mohamad ◽  
Mohd Roslan Sulaiman ◽  
Enoch Kumar Perimal
Keyword(s):  
Neuropathic Pain ◽  
Receptor Antagonist ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Mice Model ◽  
Post Surgery ◽  
Way 100635 ◽  
The Central Nervous System ◽  
Serotonergic Pathway ◽  
Pain Symptoms

Cardamonin, a naturally occurring chalcone isolated from Alpinia species has shown to possess strong anti-inflammatory and anti-nociceptive activities. Previous studies have demonstrated that cardamonin exerts antihyperalgesic and antiallodynic properties in chronic constriction injury (CCI)-induced neuropathic pain animal model. However, the mechanisms underlying cardamonin’s effect have yet to be fully understood. The present study aims to investigate the involvement of the serotonergic system in cardamonin induced antihyperalgesic and antiallodynic effects in CCI-induced neuropathic pain mice model. The neuropathic pain symptoms in the CCI mice model were assessed using Hargreaves Plantar test and von-Frey filament test on day 14 post-surgery. Central depletion of serotonin along the descending serotonergic pathway was done using ρ-chlorophenylalanine (PCPA, 100 mg/kg, i.p.), an inhibitor of serotonin synthesis for four consecutive days before cardamonin treatment, and was found to reverse the antihyperalgesic and antiallodynic effect produced by cardamonin. Pretreatment of the mice with several 5-HT receptor subtypes antagonists: methiothepin (5-HT1/6/77 receptor antagonist, 0.1 mg/kg), WAY 100635 (5-HT1A receptor antagonist, 1 mg/kg), isamoltane (5-HT1B receptor antagonist, 2.5 mg/kg), ketanserin (5-HT2A receptor antagonist, 0.3 mg/kg), and ondansetron (5-HT3 receptor antagonist, 0.5 mg/kg) were shown to abolish the effect of cardamonin induced antihyperalgesic and antiallodynic effects. Further evaluation of the 5-HT1A receptor subtype protein expressions reveals that cardamonin significantly upregulated its expression in the brainstem and spinal cord. Our results suggest that the serotonergic pathway is essential for cardamonin to exert its antineuropathic effect in CCI mice through the involvement of the 5-HT1A receptor subtype in the central nervous system.

Are transcription factors NF-κB and AP-1 involved in the ANG II-stimulated production of proinflammatory cytokines induced by LPS in dehydrated rats?

2005 ◽  
Vol 289 (6) ◽  
pp. R1599-R1608 ◽  
Author(s):  
Kumiko Sasaki ◽  
Makoto Taniguchi ◽  
Michio Miyoshi ◽  
Osamu Goto ◽  
Kenzo Sato ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Receptor Antagonist ◽  
Intravenous Injection ◽  
Proinflammatory Cytokines ◽  
Ace Inhibitor ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hepatic Expression

We recently reported an involvement of ANG II and the ANG II type 1 (AT1) receptor in the hepatic expression of IL-1β induced in dehydrated rats by LPS. Here, we first confirmed that ANG II and AT1 receptors contribute to the LPS-induced increase in the splenic concentration of IL-1β in dehydrated rats. We then investigated whether ANG II contributes to IL-1 production through a modulating effect on the activation of proinflammatory transcription factors (NF-κB and AP-1) that is induced in the dehydrated rat's liver and spleen by intravenous injection of LPS. Surprisingly, LPS markedly increased the hepatic activation of NF-κB, an effect that was significantly enhanced (rather than reduced) by pretreatment with an ANG-converting-enzyme (ACE) inhibitor or AT1-receptor antagonist. Furthermore, the same ACE inhibitor and AT1-receptor antagonist each increased the resting NF-κB activity in the liver and spleen, although they had no effect on the LPS-induced splenic expression of NF-κB. Both hepatic and splenic AP-1 expressions were enhanced by LPS. This response was significantly augmented by pretreatment with the AT1-receptor antagonist (but not with the ACE inhibitor) in the spleen, while in the liver, neither drug had any effect. These results suggest that the endogenous ANG II or AT1 receptor suppresses the activation of hepatic or splenic transcription factors in dehydrated rats given LPS. Our results seem not to support the idea that NF-κB and AP-1 play key roles in the ANG II-induced enhancement of the production of proinflammatory cytokines that is induced by LPS in dehydrated rats.

scholarly journals Effect of Bicuculline on Thalamic Activity: A Direct Blockade of I AHP in Reticularis Neurons

1998 ◽  
Vol 79 (6) ◽  
pp. 2911-2918 ◽  
Author(s):  
Franck Debarbieux ◽  
Jennifer Brunton ◽  
Serge Charpak
Keyword(s):  
Receptor Antagonist ◽  
Brain Regions ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Receptor Subtype ◽  
Sk Channels ◽  
Patch Clamp Technique ◽  
Spike Burst ◽  
Gabaergic Synapses ◽  
Low Threshold

Debarbieux, Franck, Jennifer Brunton, and Serge Charpak. Effect of bicuculline on thalamic activity: a direct blockade of I AHP in reticularis neurons. J. Neurophysiol. 79: 2911–2918, 1998. The thalamic reticular nucleus (RTN) is the major source of inhibitory contacts in the thalamus and thus plays an important role in regulating the excitability of the thalamocortical network. Inhibition occurs through GABAergic synapses on relay cells as well as through GABAergic synapses between reticularis neurons themselves. Here we report that the role and mechanisms of this inhibition, which frequently have been studied using N-methyl derivatives of the γ-aminobutyric acid-A (GABAA) receptor antagonist bicuculline, should be revisited. Using the whole cell patch-clamp technique in thalamic slices from young rats, we observed an enhancement by bicuculline methiodide, methobromide, and methochloride (collectively referred to as bicuculline-M; 5–60 μM) of the low-threshold calcium spike burst in RTN neurons that persisted in the presence of tetrodotoxin (1 μM) and was not reproduced in picrotoxin (100–300 μM). The effect did not involve activation of any GABA receptor subtype. Voltage-clamp recordings showed that bicuculline-M blocked the current underlying the low-threshold spike burst afterhyperpolarization (AHP), an effect that was mimicked by apamin (100 nM). Recordings from nucleated patches extracted from reticularis neurons demonstrated that this effect was not mediated by modulation of the release of an unidentified neurotransmitter but that bicuculline-M directly blocks small conductance (SK) channels. The AHP-blocking effect also was observed in other brain regions, demonstrating that although bicuculline-M is a potent GABAA receptor antagonist, it is of limited value in assessing GABAergic network interactions, which should be studied using picrotoxin or bicuculline-free base. However, bicuculline-M may provide a useful tool for developing nonpeptide antagonists of SK channels.

scholarly journals Differential expression of five prosomatostatin genes in the central nervous system of the catshark Scyliorhinus canicula

2019 ◽  
Author(s):  
Daniel Sobrido-Cameán ◽  
Herve Tostivint ◽  
Sylvie Mazan ◽  
María Celina Rodicio ◽  
Isabel Rodríguez-Moldes ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Differential Expression ◽  
Brain Regions ◽  
Central Canal ◽  
Scyliorhinus Canicula ◽  
The Central Nervous System ◽  
Reticular Neurons ◽  
Different Populations ◽  
The Brain

ABSTRACTFive prosomatostatin genes (PSST1, PSST2, PSST3, PSST5 and PSST6) have been recently identified in elasmobranchs (Tostivint, Gaillard, Mazan, & Pézeron, 2019). In order to gain insight into the contribution of each somatostatin to specific nervous systems circuits and behaviors in this important jawed vertebrate group, we studied the distribution of neurons expressing PSST mRNAs in the catshark Scyliorhinus canicula using in situ hybridization with specific probes for the five PSSTs transcripts. Additionally, we combined in situ hybridization with tyrosine hydroxylase (TH) immunochemistry for better localization of some PSSTs-positive populations. The five PSST genes showed expression in the brain, although with important differences in distribution. PSST1 and PSST6 were widely expressed in different brain regions. Instead, PSST2 and PSST3 were expressed only in the ventral hypothalamus and in some hindbrain lateral reticular neurons, whereas PSST5 was only expressed in the region of the entopeduncular nucleus. PSST1 and PSST6 were expressed by numerous pallial neurons, although in different populations judging from the colocalization of tyrosine hydroxylase (TH) immunoreactivity and PSST6 expression in pallial neurons and the absence of colocalization between TH and PSST1 expression. Differential expression of PSST1 and PSST6 was also observed in the subpallium, hypothalamus, diencephalon, optic tectum, midbrain tegmentum and rhombencephalon. Expression of PSST1 was observed in numerous cerebrospinal fluid-contacting (CSF-c) neurons of the paraventricular organ of the hypothalamus and the central canal of the spinal cord. These wide differences in expression of PSST genes together with the numerous brain nuclei expressing PSSTs, indicate that catshark somatostatinergic neurons are implicated differentially in a number of neural circuits.

RAS in the Central Nervous System: Potential Role in Neuropsychiatric Disorders

2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neuropsychiatric Disorders ◽  
Extensive Literature ◽  
Ang Ii ◽  
Mas Receptor ◽  
The Central Nervous System ◽  
The Brain

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.

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