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Journal of Pharmacological Sciences Mar 2021Astrocytes are glial cells with numerous fine processes which are important for the functions of the central nervous system. The activation of β-adrenoceptors induces...
Astrocytes are glial cells with numerous fine processes which are important for the functions of the central nervous system. The activation of β-adrenoceptors induces process formation of astrocytes via cyclic AMP (cAMP) signaling. However, the role of α-adrenoceptors in the astrocyte morphology has not been elucidated. Here, we examined it by using cultured astrocytes from neonatal rat spinal cords and cortices. Exposure of these cells to noradrenaline and the β-adrenoceptor agonist isoproterenol increased intracellular cAMP levels and induced the formation of processes. Noradrenaline-induced process formation was enhanced with the α-adrenoceptor antagonist prazosin and α-adrenoceptor antagonist atipamezole. Atipamezole also enhanced noradrenaline-induced cAMP elevation. Isoproterenol-induced process formation was not inhibited by the α-adrenoceptor agonist phenylephrine but was inhibited by the α-adrenoceptor agonist dexmedetomidine. Dexmedetomidine also inhibited process formation induced by the adenylate cyclase activator forskolin and the membrane-permeable cAMP analog dibutyryl-cAMP. Moreover, dexmedetomidine inhibited cAMP-independent process formation induced by adenosine or the Rho-associated kinase inhibitor Y27632. In the presence of propranolol, noradrenaline inhibited Y27632-induced process formation, which was abolished by prazosin or atipamezole. These results demonstrate that α-adrenoceptors inhibit both cAMP-dependent and -independent astrocytic process formation.
Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Adrenergic beta-Agonists; Animals; Astrocytes; Cells, Cultured; Cyclic AMP; Dexmedetomidine; Imidazoles; Isoproterenol; Norepinephrine; Prazosin; Rats, Wistar; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Signal Transduction; Rats
PubMed: 33602503
DOI: 10.1016/j.jphs.2020.12.005 -
Psychiatry Investigation May 2021A central adrenergic hyperactivation is described in the neurobiology of posttraumatic stress disorder (PTSD) with probable variable symptomatic impact. Few studies have...
OBJECTIVE
A central adrenergic hyperactivation is described in the neurobiology of posttraumatic stress disorder (PTSD) with probable variable symptomatic impact. Few studies have evaluated using the alpha-1 adrenergic antagonist prazosin for such symptoms; however, given the likely pathophysiology involved, this drug may play an important role in the pharmacological approach to PTSD.
METHODS
This study assessed articles already published on the use of prazosin through a systematic review along a timeline in view of the symptomatic target of difficult access by standardized treatments. The impact of using this medication for the general symptoms of PTSD is also discussed. Several databases were searched for articles in the literature on the use of prazosin to treat PTSD.
RESULTS
A total of 168 articles were found containing search terms in the title or abstract. Overall, 85 articles met the criteria described, and 48 studies were explored to conduct the present systematic review. Most articles showed some improvement after prazosin administration, especially in relation to sleep symptoms (nightmares and night waking). Only one article demonstrated no improvement after the use of this drug. More randomized studies are needed.
CONCLUSION
Several clinical studies demonstrated the relevant role of prazosin for treating PTSD symptoms. Prazosin is an affordable and cost-effective pharmacological option compared to other drugs used to treat PTSD.
PubMed: 33979949
DOI: 10.30773/pi.2020.0411 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Jan 2021Post-traumatic stress disorder (PTSD) is characterized by intrusive emotional memory, alertness and avoidance after individuals suffer from one or more traumatic events.... (Review)
Review
Post-traumatic stress disorder (PTSD) is characterized by intrusive emotional memory, alertness and avoidance after individuals suffer from one or more traumatic events. With the exception of manifestations, sleep disturbances are also considered to be the core symptoms of PTSD. This article mainly discussed insomnia, nightmares, obstructive sleep apnea (OSA), and periodic limb movement during sleep (PLMS) in patients with PTSD. Existing evidence suggested that insomnia is a predictor of the development of PTSD. Cognitive behavioral therapy for insomnia is an important research direction for treating insomnia in PTSD patients. Nightmares are also the core symptom of PTSD. Prazosin and image rehearsal therapy are effective therapies to treat post-traumatic nightmares. The co-occurrence of obstructive sleep apnea (OSA) is over 40% in patients with PTSD. Preliminary studies have shown that continuous positive airway pressure therapy can improve PTSD symptoms in patients with PTSD comorbid OSA. In the process of diagnosis and treatment of PTSD patients, it is important to firstly evaluate whether PTSD patient comorbid OSA or insomnia, and then clinicians could further develop an appropriate treatment plan for these patients.
Topics: Continuous Positive Airway Pressure; Dreams; Humans; Sleep; Sleep Wake Disorders; Stress Disorders, Post-Traumatic
PubMed: 33474885
DOI: 10.12182/20210160201 -
Frontiers in Immunology 2022Catecholamines such as norepinephrine or epinephrine have been reported to participate in the development of acute respiratory distress syndrome (ARDS) by activating...
α-adrenoceptor stimulation ameliorates lipopolysaccharide-induced lung injury by inhibiting alveolar macrophage inflammatory responses through NF-κB and ERK1/2 pathway in ARDS.
INTRODUCTION
Catecholamines such as norepinephrine or epinephrine have been reported to participate in the development of acute respiratory distress syndrome (ARDS) by activating adrenergic receptors (ARs). But the role of α1-AR in this process has yet to be elucidated.
METHODS
In this study, ARDS mouse model was induced by intratracheal instillation of lipopolysaccharide. After treatment with α1-AR agonist phenylephrine or antagonist prazosin, lung pathological injury, alveolar barrier disruption and inflammation, and haemodynamic changes were evaluated. Cytokine levels and cell viability of alveolar macrophages were measured in vitro. Nuclear factor κB (NF-κB), mitogen-activated protein kinase, and Akt signalling pathways were analysed by western blot.
RESULTS
It showed that α1-AR activation alleviated lung injuries, including reduced histopathological damage, cytokine expression, and inflammatory cell infiltration, and improved alveolar capillary barrier integrity of ARDS mice without influencing cardiovascular haemodynamics. experiments suggested that α1-AR stimulation inhibited secretion of TNF-α, IL-6, CXCL2/MIP-2, and promoted IL-10 secretion, but did not affect cell viability. Moreover, α1-AR stimulation inhibited NF-κB and enhanced ERK1/2 activation without significantly influencing p38, JNK, or Akt activation.
DISCUSSION
Our studies reveal that α1-AR stimulation could ameliorate lipopolysaccharide-induced lung injury by inhibiting NF-κB and promoting ERK1/2 to suppress excessive inflammatory responses of alveolar macrophages.
Topics: Mice; Animals; NF-kappa B; Macrophages, Alveolar; MAP Kinase Signaling System; Lung Injury; Lipopolysaccharides; Proto-Oncogene Proteins c-akt; Respiratory Distress Syndrome; Cytokines; Receptors, Adrenergic
PubMed: 36685596
DOI: 10.3389/fimmu.2022.1090773 -
American Journal of Veterinary Research Feb 2020To examine the effects of imidazoline and nonimidazoline α-adrenergic agents on aggregation of feline platelets.
Effects of imidazoline and nonimidazoline α-adrenoceptor agonists and antagonists, including xylazine, medetomidine, dexmedetomidine, yohimbine, and atipamezole, on aggregation of feline platelets.
OBJECTIVE
To examine the effects of imidazoline and nonimidazoline α-adrenergic agents on aggregation of feline platelets.
SAMPLE
Blood samples from 12 healthy adult cats.
PROCEDURES
In 7 experiments, the effects of 23 imidazoline and nonimidazoline α-adrenoceptor agonists or antagonists on aggregation and antiaggregation of feline platelets were determined via a turbidimetric method. Collagen and ADP were used to initiate aggregation.
RESULTS
Platelet aggregation was not induced by α-adrenoceptor agonists alone. Adrenaline and noradrenaline induced a dose-dependent potentiation of ADP- or collagen-induced aggregation. Oxymetazoline and xylometazoline also induced a small potentiation of ADP-stimulated aggregation, but other α-adrenoceptor agonists did not induce potentiation. The α-adrenoceptor antagonists and certain imidazoline α-adrenergic agents including phentolamine, yohimbine, atipamezole, clonidine, medetomidine, and dexmedetomidine inhibited adrenaline-potentiated aggregation induced by ADP or collagen in a dose-dependent manner. The imidazoline compound antazoline inhibited adrenaline-potentiated aggregation in a dose-dependent manner. Conversely, α-adrenoceptor antagonists and nonimidazoline α-adrenergic agents including xylazine and prazosin were ineffective or less effective for inhibiting adrenaline-potentiated aggregation. Moxonidine also was ineffective for inhibiting adrenaline-potentiated aggregation induced by collagen. Medetomidine and xylazine did not reverse the inhibitory effect of atipamezole and yohimbine on adrenaline-potentiated aggregation.
CONCLUSIONS AND CLINICAL RELEVANCE
Adrenaline-potentiated aggregation of feline platelets may be mediated by α-adrenoceptors, whereas imidazoline agents may inhibit in vitro platelet aggregation via imidazoline receptors. Imidazoline α-adrenergic agents may have clinical use for conditions in which there is platelet reactivity to adrenaline. Xylazine, medetomidine, and dexmedetomidine may be used clinically in cats with minimal concerns for adverse effects on platelet function.
Topics: Adrenergic alpha-Antagonists; Animals; Blood Platelets; Cats; Dexmedetomidine; Imidazoles; Imidazolines; Medetomidine; Xylazine; Yohimbine
PubMed: 31985287
DOI: 10.2460/ajvr.81.2.159 -
Clinical Psychopharmacology and... May 2020The timing of administration of pharmacologic agents is crucial in traumatic stress since they can either potentiate the original fear memory or may cause fear...
OBJECTIVE
The timing of administration of pharmacologic agents is crucial in traumatic stress since they can either potentiate the original fear memory or may cause fear extinction depending on the phase of fear conditioning. Brain noradrenergic system has a role in fear conditioning. Data regarding the role of prazosin in traumatic stress are controversial.
METHODS
In this study, we examined the effects of prazosin and the noradrenergic system in fear conditioning in a predator stress rat model. We evaluated the direct or indirect effects of stress and prazosin on noradrenaline (NA), gamma-aminobuytyric acid (GABA), glutamate, glycine levels and choline esterase activity in the amygdaloid complex, the dorsal hippocampus, the prefrontal cortex and the rostral pons.
RESULTS
Our results demonstrated that prazosin might alleviate defensive behaviors and traumatic stress symptoms when given during the traumatic cue presentation in the stressed rats. However prazosin administration resulted in higher anxiety levels in non stressed rats when the neutral cue was presented.
CONCLUSION
Prazosin should be used in PTSD with caution because prazosin might exacerbate anxiety in non-traumatized subjects. However prazosin might as well alleviate stress responses very effectively. Stress induced changes included increased NA and GABA levels in the amygdaloid complex in our study, attributing noradrenaline a possible inhibitory role on fear acquisition. Acetylcholine also has a role in memory modulation in the brain. We also demonstrated increased choline esterase acitivity. Cholinergic modulation might be another target for indirect prazosin action which needs to be further studied.
PubMed: 32329303
DOI: 10.9758/cpn.2020.18.2.219 -
Physiological Reports Jan 2021Black individuals exhibit increased blood pressure (BP) responses to sympathetic stimulation that are associated with an increased risk of hypertension (HTN). We tested... (Randomized Controlled Trial)
Randomized Controlled Trial
Black individuals exhibit increased blood pressure (BP) responses to sympathetic stimulation that are associated with an increased risk of hypertension (HTN). We tested the hypothesis that α -adrenergic blockade inhibits the increased BP response during and after 45-min stress in young normotensive Black adults, which may be mediated, in part, by dampened vasoconstriction and decreased renal sodium retention. Utilizing a double-masked randomized, crossover study design, 51 normotensive Black adults (31 ± 8 yr) were treated with either a placebo or 1 mg/day of prazosin for 1 week. On the final day of each treatment, hemodynamic measures and urinary sodium excretion (UNaV) were collected before (Rest), during (Stress) and after (Recovery) 45 min of mental stress induced via a competitive video game task. During the Stress period, diastolic BP and total peripheral resistance (TPR) were significantly lower with prazosin compared to placebo (p < .05 for both). Similarly, we observed lower systolic BP, diastolic BP, and TPR during the Recovery period with prazosin versus placebo (p < .05 for both). There was no effect of prazosin on stress-associated UNaV. The change in systolic BP from Rest to Recovery was positively associated with the change in TPR with both treatments (p < .05 for both). In summary, prazosin treatment dampened BP reactivity to 45-min mental stress and lowered post-stress BP over the recovery period, which was linked to reduce TPR in young normotensive Black adults. These results suggest that α -adrenergic receptor activity may contribute to BP responses and delayed BP recovery to prolonged mental stress through increased vasoconstriction in Black adults.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adult; Black People; Blood Pressure; Female; Humans; Male; Prazosin; Reflex; Sodium; Stress, Psychological
PubMed: 33356011
DOI: 10.14814/phy2.14642 -
Oxidative Medicine and Cellular... 2022Doxazosin and carvedilol have been evaluated as an alternative treatment against chronic liver lesions and for their possible role during the regeneration of damage...
Doxazosin and carvedilol have been evaluated as an alternative treatment against chronic liver lesions and for their possible role during the regeneration of damage caused by liver fibrosis in a hamster model. However, these drugs have been reported to induce morphological changes in hepatocytes, affecting the recovery of liver parenchyma. The effects of these /𝛽 adrenoblockers on the viability of hepatocytes are unknown. Herein, we demonstrate the protective effect of curcumin against the possible side effects of doxazosin and carvedilol, drugs with proven antifibrotic activity. After pretreatment with 1 M curcumin for 1 h, HepG2 cells were exposed to 0.1-25 M doxazosin or carvedilol for 24, 48, and 72 h. Cell viability was assessed using the MTT assay and SYTOX green staining. Morphological changes were detected using the hematoxylin and eosin (H&E) staining and scanning electron microscopy (SEM). An expression of apoptotic and oxidative stress markers was analyzed using reverse transcription-quantitative PCR (RT-qPCR). The results indicate that doxazosin decreases cell viability in a time- and dose-dependent manner, whereas carvedilol increases cell proliferation; however, curcumin increases or maintains cell viability. SEM and H&E staining provided evidence that doxazosin and carvedilol induced morphological changes in HepG2 cells, and curcumin protected against these effects, maintaining the morphology in 90% of treated cells. Furthermore, curcumin positively regulated the expression of , , and mRNAs in cells treated with 0.1 and 0.5 M doxazosin. Moreover, the / ratio was higher in cells that were treated with curcumin before doxazosin or carvedilol. The present study demonstrates that curcumin controls doxazosin- and carvedilol-induced cytotoxicity and morphological changes in HepG2 cells possibly by overexpression of .
Topics: Apoptosis; Carvedilol; Cell Membrane Permeability; Cell Proliferation; Cell Survival; Curcumin; Doxazosin; Gene Expression; Hep G2 Cells; Hepatocytes; Humans; NF-E2-Related Factor 2; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2
PubMed: 35189631
DOI: 10.1155/2022/6085515 -
Cellular Physiology and Biochemistry :... May 2024Adrenaline quickly inhibits the release of histamine from mast cells. Besides β2-adrenergic receptors, several in vitro studies also indicate the involvement of...
BACKGROUND/AIMS
Adrenaline quickly inhibits the release of histamine from mast cells. Besides β2-adrenergic receptors, several in vitro studies also indicate the involvement of α-adrenergic receptors in the process of exocytosis. Since exocytosis in mast cells can be detected electrophysiologically by the changes in the membrane capacitance (Cm), its continuous monitoring in the presence of drugs would determine their mast cell-stabilizing properties.
METHODS
Employing the whole-cell patch-clamp technique in rat peritoneal mast cells, we examined the effects of adrenaline on the degranulation of mast cells and the increase in the Cm during exocytosis. We also examined the degranulation of mast cells in the presence or absence of α-adrenergic receptor agonists or antagonists.
RESULTS
Adrenaline dose-dependently suppressed the GTP-γ-S-induced increase in the Cm and inhibited the degranulation from mast cells, which was almost completely erased in the presence of butoxamine, a β2-adrenergic receptor antagonist. Among α-adrenergic receptor agonists or antagonists, high dose prazosin, a selective α1-adrenergic receptor antagonist, significantly reduced the ratio of degranulating mast cells and suppressed the increase in the Cm. Additionally, prazosin augmented the inhibitory effects of adrenaline on the degranulation of mast cells.
CONCLUSION
This study provided electrophysiological evidence for the first time that adrenaline dose-dependently inhibited the process of exocytosis, confirming its usefulness as a potent mast cell-stabilizer. The pharmacological blockade of α1-adrenergic receptor by prazosin synergistically potentiated such mast cell-stabilizing property of adrenaline, which is primarily mediated by β2-adrenergic receptors.
Topics: Animals; Mast Cells; Epinephrine; Rats; Prazosin; Cell Degranulation; Male; Exocytosis; Patch-Clamp Techniques; Adrenergic alpha-1 Receptor Antagonists; Rats, Wistar
PubMed: 38852193
DOI: 10.33594/000000703 -
Current Issues in Molecular Biology Jan 2022Pacliatxel is a taxol-based chemotherapeutic drug that is widely used to treat cancer. However, it can also induce peripheral neuropathy, which limits its use. Although...
Pacliatxel is a taxol-based chemotherapeutic drug that is widely used to treat cancer. However, it can also induce peripheral neuropathy, which limits its use. Although several drugs are prescribed to attenuate neuropathies, no optimal treatment is available. Thus, in our study, we analyzed whether SH003 and its sub-components could alleviate paclitaxel-induced neuropathic pain. Multiple paclitaxel injections (cumulative dose 8 mg/kg, i.p.) induced cold and mechanical allodynia from day 10 to day 21 after the first injection in mice. Oral administration of SH003, an herbal mixture extract of , , and Maximowicz (Tk), dose-dependently attenuated both allodynia. However, when administered separately only Tk decreased both allodynia. The effect of Tk was shown to be mediated by the spinal noradrenergic system as intrathecal pretreatment with α- and α-adrenergic-receptor antagonists (prazosin and idazoxan), but not 5-HT, and 5-HT-receptor antagonists (methysergide and MDL-72222) blocked the effect of Tk. The spinal noradrenaline levels were also upregulated. Among the phytochemicals of Tk, cucurbitacin D was shown to play a major role, as 0.025 mg/kg (i.p.) of cucurbitacin D alleviated allodynia similar to 500 mg/kg of SH003. These results suggest that Tk should be considered when treating paclitaxel-induced neuropathic pain.
PubMed: 35723335
DOI: 10.3390/cimb44020050