scholarly journals The effects of estrogen on the α2-adrenergic receptor subtypes in rat uterine function in late pregnancy in vitro

2016 ◽  
Vol 57 (2) ◽  
pp. 100-109 ◽  
Author(s):  
Judit Hajagos-Tóth ◽  
Judit Bóta ◽  
Eszter Ducza ◽  
Adrienn Csányi ◽  
Zita Tiszai ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Late Pregnancy ◽  
Receptor Subtypes ◽  
Uterine Function

scholarly journals Role of α1-adrenergic receptor subtypes in contractility of the rabbit abdominal aorta in vitro

2013 ◽  
Vol 82 (3) ◽  
pp. 331-336 ◽  
Author(s):  
Jan Gnus ◽  
Albert Czerski ◽  
Stanisław Ferenc ◽  
Wojciech Zawadzki ◽  
Wojciech Witkiewicz ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Abdominal Aorta ◽  
Adrenergic Receptor ◽  
Receptor Subtypes ◽  
Organ Bath ◽  
Dependent Manner ◽  
Receptor Antagonists ◽  
Selective Antagonists

Investigation of the effect of α1-adrenergic receptor subtypes on the contraction of the abdominal aorta will allow for more effective treatment of hypertension by use of selective antagonists. The aim of the study was to evaluate the participation of α1-adrenergic receptor subtypes in the contractility of the aortic smooth muscle cells in rabbits. The in vitro experiments were performed in isolated tissue preparations from 30 adult female New Zealand rabbits. The abdominal aortic sections were placed in organ bath chambers and contracted with increasing doses of non-selective α1-adrenergic receptor agonist phenylephrine without pre-incubation or after incubation in α1-adrenergic receptor subtype-selective or non-selective antagonists. Separate sections were incubated with increasing concentrations of antagonists. Phenylephrine caused maximal rise in arterial smooth muscle tone to 4.75 ± 0.47 mN. The most potent in blocking phenylephrine induced contraction was 5-metylurapidil (α1A-adrenergic receptor antagonist) followed by phentolamine and prazosin (non-selective α1-adrenergic receptor antagonists); BMY 7378 (α1D-adrenergic receptor antagonist), cyclazosin and L-765.314 (α1B-adrenergic receptor antagonists) were less effective. All antagonists, except BMY 7378 elicited relaxation of non-precontracted aorta in dose dependent manner. Our results indicate that postsynaptic α1A receptors are the most potent in producing rabbit abdominal aorta contraction, while α1B and α1D subtypes are less effective.

scholarly journals α-1-Adrenergic Receptor Agonist Activity of Clinical α-Adrenergic Receptor Agonists Interferes with α-2-Mediated Analgesia

2009 ◽  
Vol 110 (2) ◽  
pp. 401-407 ◽  
Author(s):  
Daniel W. Gil ◽  
Cynthia V. Cheevers ◽  
Karen M. Kedzie ◽  
Cynthia A. Manlapaz ◽  
Sandhya Rao ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Adrenergic Receptor ◽  
Receptor Agonist ◽  
Intraperitoneal Administration ◽  
Analgesic Efficacy ◽  
Therapeutic Window ◽  
Receptor Subtypes ◽  
Agonist Activity ◽  
Wild Type

Background The use of alpha-2 adrenergic agonists for analgesia is limited due to a narrow therapeutic window. Definition of the role of alpha receptor subtypes in alpha agonist mediated analgesia may identify strategies to separate the analgesic from sedative and cardiovascular effects. Methods Analgesic activity of brimonidine, clonidine, and tizanidine was investigated in wild-type C57B/6, alpha-2A, and alpha-2C knockout mice with allodynia induced by N-methyl-D-aspartate or sulprostone. The alpha receptor selectivity of the alpha agonists was assessed using functional in vitro recombinant assays. Results Brimonidine, clonidine, and tizanidine reduced N-methyl-D-aspartate- and sulprostone-induced allodynia in wild-type mice, but not alpha-2A knockout mice. In alpha-2C knockout mice, brimonidine and tizanidine reduced allodynia in both models, whereas clonidine only reduced N-methyl-D-aspartate-induced allodynia. In vitro, clonidine and tizanidine activated alpha-1 and alpha-2 receptors with similar potencies, whereas brimonidine was selective for alpha-2 receptors. In alpha-2C knockout mice with sulprostone-induced allodynia, blockade of clonidine's alpha-1 receptor agonist activity restored clonidine's analgesic efficacy. In wild-type mice, the analgesic potency of intrathecal clonidine and tizanidine was increased 3- to 10-fold by coadministration with the alpha-1A-selective antagonist 5-methylurapidil without affecting sedation. Following intraperitoneal administration, the therapeutic window was negligible for clonidine and tizanidine, but greater for brimonidine. 5-Methylurapidil enhanced the therapeutic window of intraperitoneal clonidine and tizanidine approximately 10-fold. Conclusions Alpha-1A receptor agonist activity can counterbalance alpha-2 receptor agonist-induced analgesia. Greater alpha-2 selectivity may enhance the therapeutic window of alpha-2 agonists in the treatment of pain.

Differential cardioprotective/cardiotoxic effects mediated by β-adrenergic receptor subtypes

2005 ◽  
Vol 289 (6) ◽  
pp. H2441-H2449 ◽  
Author(s):  
Daniel Bernstein ◽  
Giovanni Fajardo ◽  
Mingming Zhao ◽  
Takashi Urashima ◽  
Jennifer Powers ◽  
...  
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Contractile Function ◽  
Cardiovascular Effects ◽  
Fold Increase ◽  
Receptor Subtypes ◽  
Wild Type ◽  
Selective Antagonist

Recent data suggest that β-adrenergic receptor subtypes couple differentially to signaling pathways regulating cardiac function vs. cardiac remodeling. To dissect the roles of β1- vs. β2-receptors in the pathogenesis of cardiomyopathy, doxorubicin was administered to β1, β2, and β1/β2 knockout (−/−) and wild-type mice. Expression and activation of MAPKs were measured. Wild-type and β1−/− mice showed no acute cardiovascular effects, whereas β2−/− mice all died within 30 min. The additional deletion of the β1-receptor (β1/β2−/−) totally rescued this toxicity. β2−/− mice developed decreased contractile function, hypotension, QTc prolongation, and ST segment changes and a 20-fold increase in p38 MAPK activity not seen in the other genotypes. The MAPK inhibitor SB-203580 rescued β2−/− mice from this acute toxicity. The enhanced toxicity in β2−/− mice was also recapitulated in wild-type mice with the β2-selective antagonist ICI-118,551, although the rescue effect of the β1-deletion was not recapitulated using the β1-selective antagonist metoprolol or the nonselective β-antagonist propranolol. These data suggest that β2-adrenergic receptors play a cardioprotective role in the pathogenesis of cardiomyopathy, whereas β1-adrenergic receptors mediate at least some of the acute cardiotoxicity of anthracyclines. Differential activation of MAPK isoforms, previously shown in vitro to regulate β-agonist as well as doxorubicin cardiotoxicity, appears to play a role in mediating the differential effects of these β-adrenergic receptor subtypes in vivo.

Piperazinylimidazo[1,2-a]pyrazines with selective affinity for in vitro .alpha.-adrenergic receptor subtypes

1983 ◽  
Vol 26 (3) ◽  
pp. 357-363 ◽  
Author(s):  
William C. Lumma ◽  
William C. Randall ◽  
E. L. Cresson ◽  
Joel R. Huff ◽  
Richard D. Hartman ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Receptor Subtypes ◽  
Alpha Adrenergic Receptor

scholarly journals The effects of progesterone on the alpha2-adrenergic receptor subtypes in late-pregnant uterine contractions in vitro

2016 ◽  
Vol 14 (1) ◽  
Author(s):  
Judit Hajagos-Tóth ◽  
Judit Bóta ◽  
Eszter Ducza ◽  
Reza Samavati ◽  
Anna Borsodi ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Receptor Subtypes ◽  
Uterine Contractions

scholarly journals Pregnancy-induced decrease in the relaxant effect of terbutaline in the late-pregnant rat myometrium: role of G-protein activation and progesterone

Reproduction ◽  
2005 ◽  
Vol 130 (1) ◽  
pp. 113-122 ◽  
Author(s):  
Róbert Gáspár ◽  
Eszter Ducza ◽  
Attila Mihályi ◽  
Árpád Márki ◽  
Zoltán Kolarovszki-Sipiczki ◽  
...  
Keyword(s):  
G Protein ◽  
Protein Level ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Mrna Level ◽  
Late Pregnancy ◽  
Plasma Progesterone ◽  
Protein Activation ◽  
G Protein Activation

The effectiveness of β2-agonists in preterm delivery is reduced by several factors. The aim of this study was to determine the influence of late pregnancy in the uterus-relaxing effect of terbutaline in the rat in vitro. Rat uterine tissues from late pregnancy (days 15, 18, 20 and 22) were used. In vitro electrical field-stimulation (EFS) was used to evoke contractions. The radioligand-binding technique, reverse transcription-polymerase chain reaction and radioimmunoassay technique were used to determine the β-adrenergic receptor density and mRNA level and the plasma sex hormone level, respectively. The activated G-protein level of the β-adrenergic receptors was investigated by a radiolabelled GTP binding assay. EFS-induced contractions were inhibited by terbutaline. This effect decreased towards term with respect to both the EC50 and maximal inhibition values. A drop in plasma progesterone level was also detected. Binding studies revealed an increase in β-adrenergic receptor number on the last day of pregnancy, which correlated with the change in receptor mRNA level. The G-protein-activating effect of terbutaline decreased continuously between days 15 and 20. Surprisingly, terbutaline decreased the G-protein activation to below the basal level on day 22. However, progesterone pretreatment set back the uterine action of terbutaline, increased the density of the β2-adrenergic receptors and their mRNA level and increased the G-protein-activating property of terbutaline. These data provide evidence of a pregnancy-induced decrease in activated G-protein level after β2-agonist stimulation. The decrease in plasma progesterone level has a crucial role in this process. The effects of β2-adrenergic receptor agonists in tocolytic therapy may possibly be potentiated with progesterone.

ChemInform Abstract: PIPERAZINYLIMIDAZO(1,2-A)PYRAZINES WITH SELECTIVE AFFINITY FOR IN VITRO α-ADRENERGIC RECEPTOR SUBTYPES

1983 ◽  
Vol 14 (34) ◽  
Author(s):  
W. C. JUN. LUMMA ◽  
W. C. RANDALL ◽  
E. L. CRESSON ◽  
J. R. HUFF ◽  
R. D. HARTMAN ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Receptor Subtypes
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