Inhibition of Glutamatergic Synaptic Input to Spinal Lamina IIo Neurons by Presynaptic α2-Adrenergic Receptors

2002 ◽  
Vol 87 (4) ◽  
pp. 1938-1947 ◽  
Author(s):  
Yu-Zhen Pan ◽  
De-Pei Li ◽  
Hui-Lin Pan
Keyword(s):  
Receptor Antagonist ◽  
Synaptic Input ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Dorsal Root ◽  
Primary Afferents ◽  
Noradrenergic System ◽  
Analgesic Action ◽  
Adrenergic Agonists ◽  
Excitatory Synaptic Input

Activation of spinal α2-adrenergic receptors by the descending noradrenergic system and α2-adrenergic agonists produces analgesia. However, the sites and mechanisms of the analgesic action of spinally administered α2-adrenergic receptor agonists such as clonidine are not fully known. The dorsal horn neurons in the outer zone of lamina II (lamina IIo) are important for processing nociceptive information from C-fiber primary afferents. In the present study, we tested a hypothesis that activation of presynaptic α2-adrenergic receptors by clonidine inhibits the excitatory synaptic input to lamina IIo neurons. Whole cell voltage-clamp recordings were performed on visualized lamina IIo neurons in the spinal cord slice of rats. The miniature excitatory postsynaptic currents (mEPSCs) were recorded in the presence of tetrodotoxin, bicuculline, and strychnine. The evoked EPSCs were obtained by electrical stimulation of the dorsal root entry zone or the attached dorsal root. Both mEPSCs and evoked EPSCs were abolished by application of 6-cyano-7-nitroquinoxaline-2,3-dione. Clonidine (10 μM) significantly decreased the frequency of mEPSCs from 5.8 ± 0.9 to 2.7 ± 0.6 Hz (means ± SE) without altering the amplitude and the decay time constant of mEPSCs in 25 of 27 lamina IIo neurons. Yohimbine (2 μM, an α2-adrenergic receptor antagonist), but not prazosin (2 μM, an α1-adrenergic receptor antagonist), blocked the inhibitory effect of clonidine on the mEPSCs. Clonidine (1–20 μM, n = 8) also significantly attenuated the peak amplitude of evoked EPSCs in a concentration-dependent manner. The effect of clonidine on evoked EPSCs was abolished in the presence of yohimbine ( n = 5). These data suggest that clonidine inhibits the excitatory synaptic input to lamina IIo neurons through activation of α2-adrenergic receptors located on the glutamatergic afferent terminals. Presynaptic inhibition of glutamate release from primary afferents onto lamina IIoneurons likely plays an important role in the analgesic action produced by activation of the descending noradrenergic system and α2-adrenergic agonists.

scholarly journals The Alpha-1 Adrenergic Receptor Antagonist Prazosin Reduces Binge-Like Eating in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1569
Author(s):  
Callum Hicks ◽  
Valentina Sabino ◽  
Pietro Cottone
Keyword(s):  
Receptor Antagonist ◽  
Adrenergic Receptor ◽  
Fixed Ratio ◽  
Progressive Ratio ◽  
Noradrenergic System ◽  
Palatable Food ◽  
Schedule Of Reinforcement ◽  
Male Wistar Rats

Background: Binge-eating disorder is a pervasive addiction-like disorder that is defined by excessive and uncontrollable consumption of food within brief periods of time. The aim of the current study was to examine the role of the brain noradrenergic system in binge-like eating through the use of the alpha-1 adrenergic receptor antagonist prazosin. Methods: For this purpose, we employed a limited access model whereby male Wistar rats were allowed to nosepoke for either chow (Chow rats) or a sugary, highly palatable food (Palatable rats) for 1 h/day. The effects of prazosin (0, 0.5, 1 and 2 mg/kg, i.p.) were tested in a fixed ratio 1 (FR1) and progressive ratio (PR) schedule of reinforcement. Results: The results show that prazosin preferentially reduced the responses for palatable food in a FR1 reinforcement schedule; when tested in a PR schedule of reinforcement, prazosin increased breakpoint in both Chow and Palatable rats, but more potently and more efficaciously in the latter. Our results suggest that prazosin treatment preferentially increased the motivational properties of the palatable diet. Conclusions: The current findings provide the characterization of the effects of prazosin on binge-like eating and offer support to the existing literature showing the important role of the noradrenergic system in addiction-like behavior.

Tachykinins mediate slow excitatory postsynaptic transmission in guinea pig sphincter of Oddi ganglia

2001 ◽  
Vol 281 (2) ◽  
pp. G357-G364 ◽  
Author(s):  
Brian P. Manning ◽  
Gary M. Mawe
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Receptor Antagonist ◽  
Synaptic Input ◽  
Intracellular Recording ◽  
Small Diameter ◽  
Sphincter Of Oddi ◽  
Receptor Desensitization ◽  
Afferent Fibers ◽  
Excitatory Synaptic Input

Intracellular recording techniques were used to test whether tachykinins could be mediators of slow excitatory postsynaptic potentials (EPSPs) in guinea pig sphincter of Oddi (SO) ganglia. Application of the tachykinin substance P (SP) onto SO neurons caused a prolonged membrane depolarization that was reminiscent of the slow EPSP in these cells. Pressure ejection of the neurokinin 3 (NK3) receptor-specific agonist senktide caused a similar depolarization; however, no responses were detected on application of NK1 or NK2 receptor agonists. The NK3 receptor antagonist SR-142801 (100 nM) significantly inhibited both SP-induced depolarization and the stimulation-evoked slow EPSP, as did NK3 receptor desensitization with senktide. Capsaicin, which causes the release of SP from small-diameter afferent fibers, induced a depolarization that was similar to the evoked slow EPSP in both amplitude and duration. The capsaicin-induced depolarization was significantly attenuated in the presence of SR-142801. These data indicate that tachykinins, released from extrinsic afferent fibers, act via NK3 receptors to provide slow excitatory synaptic input to SO neurons.

Role of supraspinal and spinal α1-adrenergic receptor subtypes in micturition reflex in conscious rats

2010 ◽  
Vol 299 (4) ◽  
pp. F785-F791 ◽  
Author(s):  
Masaru Yoshizumi ◽  
Kazumasa Matsumoto-Miyai ◽  
Akihiko Yonezawa ◽  
Masahito Kawatani
Keyword(s):  
Spinal Cord ◽  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Intrathecal Injection ◽  
Receptor Subtypes ◽  
Lumbosacral Spinal Cord ◽  
Micturition Reflex ◽  
Conscious Rats

α1-Adrenergic receptor subtypes are widely distributed in the central nervous system and are involved in autonomic functions such as micturition. We investigated the presence and the role of supraspinal and/or spinal α1-adrenergic receptors in modulating the micturition reflex in conscious female Wistar rats. The expression of α1-adrenergic receptor subtypes in rat brain and lumbosacral spinal cord was studied using RT-PCR. Continuous-infusion cystometrograms were obtained in conscious rats, and α1-adrenergic receptor antagonists were administered via intracerebroventricular or intrathecal routes. The mRNA expression of α1A-, α1B-, and α1D-adrenergic receptors was detected in rat brain (midbrain and pons) and lumbosacral spinal cord (dorsal and ventral parts of spinal cord). In addition, intracerebroventricular injection of the α1-adrenergic receptor antagonist tamsulosin (1–10 μg), the selective α1A-adrenergic receptor antagonist silodosin (1–10 μg), and the selective α1D-adrenergic receptor antagonist BMY 7378 (1–10 μg) significantly prolonged the intercontraction interval (ICI) but did not alter maximum voiding pressure (MVP). Although intrathecal injection of BMY 7378 (0.0001–10 μg) did not affect ICI, tamsulosin and silodosin prolonged ICI in a dose-dependent manner. MVP was significantly reduced by intrathecal injection of tamsulosin (10 μg) but not by silodosin or BMY 7378 (0.0001–10 μg). Supraspinal α1A- and α1D-adrenergic receptors are apparently important for the regulation of reflex-bladder activity in conscious rats. Noradrenergic projection from the brain stem to the lumbosacral spinal cord may promote the afferent limb rather than the efferent limb of the micturition reflex pathway via α1A-adrenergic receptors.

Interaction between prolactin and catecholamines on hypothalamic GnRH release in vitro

1996 ◽  
Vol 151 (2) ◽  
pp. 269-275 ◽  
Author(s):  
A E Calogero ◽  
N Burrello ◽  
A M Ossino ◽  
R F A Weber ◽  
R D'Agata
Keyword(s):  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Experimental Conditions ◽  
Adrenergic Mechanism ◽  
Gnrh Release ◽  
Β Adrenergic Receptors

Abstract Brain catecholamines have been implicated in the regulation of gonadotrophin release. It has been recently reported that noradrenaline (NA), applied within the hypothalamic paraventricular nucleus, suppresses the pulsatile release of LH in the rat through a corticotrophin-releasing hormone (CRH)-dependent mechanism. Prolactin (PRL) is also able to suppress hypothalamic GnRH release following activation of the CRH-releasing neurone. Given that PRL stimulates the release of NA from hypothalamic explants and that NA stimulates the release of hypothalamic CRH, we hypothesized that this neurotransmitter may be involved in the intrahypothalamic neuroendocrine circuit mediating the inhibitory effects of PRL on GnRH release. To test this hypothesis, we evaluated the effects of PRL on GnRH release in the presence of α- or β-adrenergic receptor antagonists using a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release from individually incubated, longitudinally halved hypothalami. As previously shown, PRL at a concentration of 100 nm inhibited basal iGnRH release by about 35%. Phentolamine, a non-selective α-adrenergic receptor antagonist, prazosin, an α1-receptor antagonist, and yohimbine, an α2-receptor antagonist, overcame the inhibitory effect of PRL on iGnRH release in a concentration-dependent fashion. In contrast, propranolol, a non-selective β-adrenergic receptor antagonist, atenolol, a β1-receptor antagonist, and ICI-118,551, a β2-receptor antagonist, had no effect. None of these compounds had any effect on basal iGnRH release. These findings suggested that an α-adrenergic mechanism is involved in the suppressive effects of PRL on GnRH release. Since the activation of α-adrenergic receptors increases hypothalamic CRH release, we evaluated whether PRL stimulates CRH release via an α-adrenergic mechanism. PRL stimulated basal CRH release by about twofold and this effect was inhibited by phentolamine in a concentration-dependent fashion. In conclusion, α-, but not β-, adrenergic receptors mediate the inhibitory effects of PRL on GnRH release in vitro. We speculate that, at least under these experimental conditions, PRL inhibits GnRH release through an α-adrenergic mechanism which activates the CRH-secreting neurone. Journal of Endocrinology (1996) 151, 269–275

scholarly journals α1-Adrenergic Receptor Blockade by Prazosin Synergistically Stabilizes Rat Peritoneal Mast Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Nozomu Abe ◽  
Hiroaki Toyama ◽  
Yutaka Ejima ◽  
Kazutomo Saito ◽  
Tsutomu Tamada ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
High Dose ◽  
Patch Clamp Technique ◽  
Receptor Agonists ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells

Background. 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. Conclusions. 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.

scholarly journals The Effect of α-Adrenergic Receptor Blockers Prazosin and Yohimbine on Cerebral Metabolism and Biogenic Amine Content of Traumatized Brain

1991 ◽  
Vol 11 (2) ◽  
pp. 242-252 ◽  
Author(s):  
Masaru Inoue ◽  
Michael McHugh ◽  
Hanna M. Pappius
Keyword(s):  
Brain Injury ◽  
Biogenic Amine ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cerebral Metabolism ◽  
Noradrenergic System ◽  
Injured Brain ◽  
Amine Content ◽  
Hydroxyindoleacetic Acid ◽  
Functional Consequences

Widespread decrease in local cerebral glucose utilization (LCGU) previously shown to occur 3 days after a focal freezing lesion was interpreted as reflecting a depression of functional activity in the affected areas. In parallel experiments, cortical norepinephrine (NE) content of traumatized brain was found to be decreased. The effects of prazosin (PZ), an α1-adrenergic receptor blocker, and yohimbine (YOH), an α2-blocker, on glucose use and biogenic amine content of lesioned rat brain were studied to determine if the changes in the noradrenergic system associated with injury are of functional importance, to identify the receptors that may be involved in mediating the action of NE in injured brain, and to look for evidence of interaction between the noradrenergic and the serotonergic systems in traumatized brain. PZ (1 mg/kg) given 30 min before the lesion ameliorated the subsequent metabolic cortical depression seen in untreated animals. PZ given for 3 days starting before the lesion (3 mg/kg/day) was also effective in normalizing LCGU in areas where it was depressed by lesioning, despite the fact that this regimen induced significant global decrease in LCGU in normal animals. Once cortical metabolic depression had developed 3 days after the lesion, it could not be modified by PZ. YOH was less effective than PZ and was so only when given for 3 days (22.5 mg/kg/day in three divided doses). PZ (3 mg/kg/day in three divided doses) slightly but significantly decreased the accumulation of the serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid in the traumatized hemisphere. These results provide evidence that blockage of α1adrenergic receptors prevents the development of cortical dysfunction associated with brain trauma. This implies that the noradrenergic system plays a role in the functional consequences of injury and that this effect is, at least in part, mediated by α1-adrenergic receptors. Furthermore, α1-adrenergic receptor blockage appears to modulate cortical turnover of 5-HT, previously also implicated in functional consequences of brain injury. The data are compatible with inhibitory effects of NE in the cortex and suggest a potential of α1-adrenergic blockage in development of novel therapeutic approaches to brain injury.

scholarly journals SAT-306 Muscarinic and Adrenergic Receptor Cooperativity in a Human Adrenocortical Carcinoma Cell Line

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Latha Malaiyandi ◽  
Alice Meyer ◽  
Nuntida Surachaicharn ◽  
Dominic Pelchat ◽  
Annette Gilchrist ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Calcium Oscillations ◽  
Binding Assays ◽  
Steroid Synthesis ◽  
M3 Receptors ◽  
Aldosterone Production ◽  
Autonomic Receptors

Abstract The role of autonomic receptors in the regulation of the adrenal cortex is poorly understood. We recently showed that activation of M3 muscarinic receptors stimulates intracellular calcium oscillations, aldosterone production, and expression of CYP11B2 (1). The present study explores the relationship between muscarinic and adrenergic receptors in corticosteroid production. Using live-cell fluorescence imaging of HAC15 adrenocortical cells with the calcium-sensitive probe Fluo-4, we have shown that stimulation of adrenergic receptors with the endogenous, non-selective adrenergic agonist norepinephrine (10μM) enhances intracellular Ca2+ oscillations caused by the cholinergic agonist carbachol (1μM). However, Ca2+ is not affected by norepinephrine alone. Adrenergic enhancement of carbachol-induced Ca2+ oscillations is blocked by the ⍺ adrenergic receptor antagonist phentolamine, but not by the β adrenergic receptor antagonist propanolol. Specifically, ⍺2 and β2 antagonists (such as yohimbine and butoxamine, respectively) significantly suppressed the norepinephrine effect, but ⍺1 and β1 antagonists (such as tamsulosin and metoprolol, respectively) had no effect. RT qPCR identified ⍺2A receptors as the most abundant adrenergic receptor in HAC15 cells. Saturation experiments using 3H-NMS and 3H-Rauwolscine confirmed the presence of muscarinic M2 and M3 receptors as well as ⍺2A receptors. Using competition radiolabeled binding assays we explored the cooperation between M2/M3 and ⍺2A adrenergic receptors. Our results suggest that autonomic regulation of intracellular Ca2+ depends on an interplay of M3 and ⍺2A receptors. Additional experiments will use ELISA methods to determine the functional impact of autonomic receptor cooperativity on steroid synthesis and secretion. References: (1) Malaiyandi et al., Mol Cell Endocrinol. 2018 478: 1-9.

Central lipopolysaccharide elevates plasma IL-6 concentration by an alpha-adrenoreceptor-mediated mechanism

1997 ◽  
Vol 272 (6) ◽  
pp. R1880-R1887 ◽  
Author(s):  
B. N. Finck ◽  
R. Dantzer ◽  
K. W. Kelley ◽  
J. A. Woods ◽  
R. W. Johnson
Keyword(s):  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Alpha Adrenergic Receptor ◽  
Inflammatory Stimuli ◽  
Dose Dependent Fashion ◽  
Subsequent Activation ◽  
Dose Dependent ◽  
The Brain ◽  
Circulating Levels

High circulating levels of interleukin-6 (IL-6) are evident after intracerebroventricular injection of lipopolysaccharide (LPS). To investigate the pathway of centrally induced IL-6 production, in the present study we evaluated the effects of specific alpha-adrenergic receptor antagonists administered peripherally on IL-6 production and hypertriglyceridemia induced by LPS administered centrally. In the first study, adult male Wistar-Furth rats were injected intracerebroventricularly with LPS. Centrally injected LPS increased plasma IL-6 and triglycerides (TG) in a dose-dependent fashion. To determine if LPS increased plasma IL-6 and TG through an alpha-adrenoreceptor mechanism, rats were pretreated intraperitoneally with either vehicle, phentolamine (alpha 1- and alpha 2-receptor antagonist), prazosin (alpha 1-receptor antagonist), or yohimbine (alpha 2-receptor antagonist). Thirty minutes later, rats were injected intracerebroventricularly with LPS. Whereas prazosin and yohimbine attenuated the increases in plasma IL-6 caused by LPS, phentolamine completely blocked the peripheral effects of central LPS. These data suggest that increased sympathetic activity and subsequent activation of alpha 1- and alpha 2-adrenergic receptors are important for controlling peripheral metabolic and endocrine systems when inflammatory stimuli are present in the brain.

scholarly journals β3-Adrenergic receptor antagonist improves exercise performance in pacing-induced heart failure

2013 ◽  
Vol 305 (6) ◽  
pp. H923-H930 ◽  
Author(s):  
Satoshi Masutani ◽  
Heng-Jie Cheng ◽  
Atsushi Morimoto ◽  
Hiroshi Hasegawa ◽  
Qing-Hua Han ◽  
...  
Keyword(s):  
Heart Failure ◽  
Receptor Antagonist ◽  
Exercise Performance ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Systolic Pressure ◽  
Mechanical Efficiency ◽  
Left Ventricular ◽  
Diastolic Filling ◽  
Stimulation Of

In heart failure (HF), the impaired left ventricular (LV) arterial coupling and diastolic dysfunction present at rest are exacerbated during exercise. We have previously shown that in HF at rest stimulation of β3-adrenergic receptors by endogenous catecholamine depresses LV contraction and relaxation. β3-Adrenergic receptors are activated at higher concentrations of catecholamine. Thus exercise may cause increased stimulation of cardiac β3-adrenergic receptors and contribute to this abnormal response. We assessed the effect of L-748,337 (50 μg/kg iv), a selective β3-adrenergic receptor antagonist (β3-ANT), on LV dynamics during exercise in 12 chronically instrumented dogs with pacing-induced HF. Compared with HF at rest, exercise increased LV end-systolic pressure (PES), minimum LV pressure (LVPmin), and the time constant of LV relaxation (τ) with an upward shift of early diastolic portion of LV pressure-volume loop. LV contractility decreased and arterial elastance (EA) increased. LV arterial coupling (EES/EA) (0.40 vs. 0.51) was impaired. Compared with exercise in HF preparation, exercise after β3-ANT caused similar increases in heart rate and PES but significantly decreased τ (34.9 vs. 38.3 ms) and LVPmin with a downward shift of the early diastolic portion of LV pressure-volume loop and further augmented dV/d tmax. Both EES and EES/EA (0.68 vs. 0.40) were increased. LV mechanical efficiency improved from 0.39 to 0.53. In conclusion, after HF, β3-ANT improves LV diastolic filling; increases LV contractility, LV arterial coupling, and mechanical efficiency; and improves exercise performance.

scholarly journals Role of beta-adrenergic receptor subtypes in pig uterus contractility with inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Barbara Jana ◽  
Jarosław Całka
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Domestic Animals ◽  
Inhibitory Effect ◽  
Receptor Subtypes ◽  
Beta Adrenergic Receptor ◽  
Pharmacological Modulation ◽  
Uterine Inflammation ◽  
Myometrial Contractility

AbstractUterine inflammation is a very common and serious condition in domestic animals. To development and progression of this pathology often lead disturbances in myometrial contractility. Participation of β1-, β2- and β3-adrenergic receptors (ARs) in noradrenaline (NA)-influenced contractility of the pig inflamed uterus was studied. The gilts of SAL- and E.coli-treated groups were administered saline or E.coli suspension into the uterine horns, respectively. Laparotomy was only done in the CON group. Compared to the period before NA administration, this neurotransmitter reduced the tension, amplitude and frequency in uterine strips of the CON and SAL groups. In the E.coli group, NA decreased the amplitude and frequency, and these parameters were lower than in other groups. In the CON, SAL and E.coli groups, β1- and β3-ARs antagonists in more cases did not significantly change and partly eliminated NA inhibitory effect on amplitude and frequency, as compared to NA action alone. In turn, β2-ARs antagonist completely abolished NA relaxatory effect on these parameters in three groups. Summarizing, NA decreases the contractile amplitude and frequency of pig inflamed uterus via all β-ARs subtypes, however, β2-ARs have the greatest importance. Given this, pharmacological modulation of particular β-ARs subtypes can be used to increase inflamed uterus contractility.

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