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.

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 Adrenergic α1 receptor activation is sufficient, but not necessary for phrenic long-term facilitation

2014 ◽  
Vol 116 (11) ◽  
pp. 1345-1352 ◽  
Author(s):  
A. G. Huxtable ◽  
P. M. MacFarlane ◽  
S. Vinit ◽  
N. L. Nichols ◽  
E. A. Dale ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Intermittent Hypoxia ◽  
Receptor Agonist ◽  
Receptor Activation ◽  
Motor Nucleus ◽  
Long Term Facilitation ◽  
Dose Dependent

Acute intermittent hypoxia (AIH; three 5-min hypoxic episodes) causes a form of phrenic motor facilitation (pMF) known as phrenic long-term facilitation (pLTF); pLTF is initiated by spinal activation of Gq protein-coupled 5-HT2 receptors. Because α1 adrenergic receptors are expressed in the phrenic motor nucleus and are also Gq protein-coupled, we hypothesized that α1 receptors are sufficient, but not necessary for AIH-induced pLTF. In anesthetized, paralyzed, and ventilated rats, episodic spinal application of the α1 receptor agonist phenylephrine (PE) elicited dose-dependent pMF (10 and 100 μM, P < 0.05; but not 1 μM). PE-induced pMF was blocked by the α1 receptor antagonist prazosin (1 mM; −20 ± 20% at 60 min, −5 ± 21% at 90 min; n = 6). Although α1 receptor activation is sufficient to induce pMF, it was not necessary for AIH-induced pLTF because intrathecal prazosin (1 mM) did not alter AIH-induced pLTF (56 ± 9% at 60 min, 78 ± 12% at 90 min; n = 9). Intravenous (iv) prazosin (150 μg/kg) appeared to reduce pLTF (21 ± 9% at 60 min, 26 ± 8% at 90 min), but this effect was not significant. Hypoglossal long-term facilitation was unaffected by intrathecal prazosin, but was blocked by iv prazosin (−4 ± 14% at 60 min, −13 ± 18% at 90 min), suggesting different LTF mechanisms in different motor neuron pools. In conclusion, Gq protein-coupled α1 adrenergic receptors evoke pMF, but they are not necessary for AIH-induced pLTF.

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 Involvement of phosphoinositide metabolism in potentiation by adrenaline of ADP-induced aggregation of rabbit platelets

1987 ◽  
Vol 242 (3) ◽  
pp. 841-847 ◽  
Author(s):  
C Lalau Keraly ◽  
J D Vickers ◽  
R L Kinlough-Rathbone ◽  
J F Mustard
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Inositol Phosphate ◽  
Phosphoinositide Metabolism ◽  
Beta Adrenergic ◽  
Alpha Adrenergic Receptor ◽  
Rabbit Platelets ◽  
Phosphatidylinositol 4 ◽  
Induced Changes ◽  
Induced Aggregation

Changes in phosphoinositide metabolism were examined in washed rabbit platelets stimulated with 0.5 microM-ADP, 50 microM-adrenaline, or ADP and adrenaline in combination. Adrenaline does not stimulate platelet aggregation when used alone, but does potentiate aggregation stimulated by ADP. In platelets prelabelled with [32P]Pi and [3H]glycerol, adrenaline was found to potentiate the ADP-induced changes in platelet phospholipids, causing larger increases in the amount and labelling of phosphatidylinositol 4-phosphate (PIP) and phosphatidic acid than was observed with ADP alone. The combination of ADP and adrenaline did not produce a greater decrease in phosphatidylinositol 4,5-bisphosphate (PIP2) than was produced by ADP alone. In platelets prelabelled with [3H]inositol, adrenaline potentiated the increases in labelling of inositol phosphate and inositol bisphosphate stimulated by ADP; no increase in inositol trisphosphate labelling was detected with ADP alone or with the combination of ADP and adrenaline. Phentolamine, an alpha-adrenergic-receptor antagonist, blocked potentiation by adrenaline of ADP-induced changes in phosphoinositide metabolism. Propranolol and sotalol, beta-adrenergic-receptor antagonists, augmented the potentiation; this is consistent with the concept that the effect of adrenaline is mediated by beta-adrenergic receptors. The effect of adrenaline on phosphoinositide metabolism appears to be to potentiate the mechanisms by which ADP causes turnover of PIP and possibly degradation of PI, rather than the mechanism by which PIP2 is decreased.

scholarly journals Alpha adrenergic receptors are involved in the contractile activity of neuropeptide Y in the porcine isolated ovarian artery

2012 ◽  
Vol 48 (No. 10) ◽  
pp. 283-292
Author(s):  
W. Markiewicz
Keyword(s):  
Blood Pressure ◽  
Neuropeptide Y ◽  
Estrous Cycle ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Contractile Activity ◽  
Steroid Hormone ◽  
Ovarian Artery ◽  
Alpha Adrenergic Receptors ◽  
Alpha Adrenergic Receptor

The objective of this study was to determine whether &alpha;-adrenergic receptors are involved in the contractile activity of neuropeptide Y (NPY) in the porcine isolated ovarian artery collected from immature pigs and from the animals on day 1&ndash;5, 8&ndash;13 and 17&ndash;20 of the estrous cycle. NPY increased (P &lt; 0.05) blood pressure in preparations collected form the immature and mature pigs. NPY administration into prazosin pre-treated vessels increased (P &lt; 0.05) blood pressure in preparations of the immature and mature animals with the highest potency in the vessels from days 17&ndash;20 of the cycle. Simultaneous methoxamine and NPY treatment caused an increase (P &lt; 0.05) in blood pressure in the vessels from all the periods examined with the highest potency in the preparations from days 17&ndash;20 of the cycle. NPY administration at the time of the maximum response to rauwolscine increased (P &lt; 0.05) blood pressure in the preparations from the immature and mature pigs with the highest changes in the preparations from days 17&ndash;20 of the cycle. In clonidine pre-treated ovarian arteries, NPY insignificantly increased (P &gt; 0.05) blood pressure in the preparations collected from the immature pigs and on days 1&ndash;5, 8&ndash;13 of the cycle, and significantly increased (P &lt; 0.05) blood pressure in preparations from the animals on days 17&ndash;20 of the oestrous cycle. The present study has revealed that NPY increases blood pressure in the isolated porcine ovarian artery and that &alpha;-adrenergic receptors are involved in the vosocontractile action of this peptide. Moreover, the changes in the blood pressure caused by NPY alone or administered after &alpha;-adrenergic receptor agonists or antagonists treatment are dependent on steroid hormone concentrations.

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 Vascular α1A Adrenergic Receptors as a Potential Therapeutic Target for IPAD in Alzheimer’s Disease

2020 ◽  
Vol 13 (9) ◽  
pp. 261
Author(s):  
Miles Frost ◽  
Abby Keable ◽  
Dan Baseley ◽  
Amber Sealy ◽  
Diana Andreea Zbarcea ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Muscle Cells ◽  
Cerebral Vessels ◽  
Cerebrovascular Smooth Muscle Cells ◽  
The Brain ◽  
Young Old

Drainage of interstitial fluid from the brain occurs via the intramural periarterial drainage (IPAD) pathways along the basement membranes of cerebral capillaries and arteries against the direction of blood flow into the brain. The cerebrovascular smooth muscle cells (SMCs) provide the motive force for driving IPAD, and their decrease in function may explain the deposition of amyloid-beta as cerebral amyloid angiopathy (CAA), a key feature of Alzheimer’s disease. The α-adrenoceptor subtype α1A is abundant in the brain, but its distribution in the cerebral vessels is unclear. We analysed cultured human cerebrovascular SMCs and young, old and CAA human brains for (a) the presence of α1A receptor and (b) the distribution of the α1A receptor within the cerebral vessels. The α1A receptor was present on the wall of cerebrovascular SMCs. No significant changes were observed in the vascular expression of the α1A-adrenergic receptor in young, old and CAA cases. The pattern of vascular staining appeared less punctate and more diffuse with ageing and CAA. Our results show that the α1A-adrenergic receptor is preserved in cerebral vessels with ageing and in CAA and is expressed on cerebrovascular smooth muscle cells, suggesting that vascular adrenergic receptors may hold potential for therapeutic targeting of IPAD.

muscle microcirculation: effects of tissue pH, PCO2, and PO2 during systemic hypoxia

1981 ◽  
Vol 240 (5) ◽  
pp. H746-H754 ◽  
Author(s):  
R. J. Morff ◽  
P. D. Harris ◽  
D. L. Wiegman ◽  
F. N. Miller
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cremaster Muscle ◽  
Third Order ◽  
First Order ◽  
Alpha Adrenergic Receptors ◽  
Alpha Adrenergic Receptor ◽  
Systemic Hypoxia ◽  
O2 Concentration ◽  
Biphasic Responses

The responses of arterioles and venules to systemic hypoxia (fractional inspired O2 concentration 0.10) were determined for the rat cremaster muscle that was positioned with intact nerve and vascular supplies in a tissue bath that had controlled pH, O2 tension (PO2), CO2 tension (PCO2), and temperature. Blood pressure and heart rate were decreased significantly during systemic hypoxia. First- and second-order arterioles actively constricted during systemic hypoxia, whereas most first-, second-, and third-order venules had biphasic responses (dilation followed by constriction). There were no significant differences in the active arteriolar responses to systemic hypoxia when cremaster bath pH was altered from 6.9 to 7.2, or when bath PCO2 was changed from 60 +/- 2.2 to less than 5 mmHg; but, there was significantly greater arteriolar constriction with high bath PO2 (139 +/- 1.3 mmHg) in comparison to low bath PO2 (4.5 +/- 0.5 mmHg). Decreased bath pH, decreased PO2, and increased PCO2 had no effect on the dilation responses of first-, and second-, and third-order venules to systemic hypoxia; however, these bath alterations attenuated the constriction responses of third-order venules. alpha-Adrenergic receptor blockade did not alter the arteriolar responses to systemic hypoxia. Our data indicate 1) that there is a centrally mediated stimulus for constriction of first-order arterioles during systemic hypoxia, 2) that changes in local cremaster PO2, but not PCO2 or pH, can attenuate this centrally mediated arteriolar constriction, and 3) that the centrally mediated arteriolar constriction does not involve alpha-adrenergic receptors.

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