Characterization of myometrial desensitization to β-adrenergic agonists

1990 ◽  
Vol 68 (10) ◽  
pp. 1377-1384 ◽  
Author(s):  
Brian A. Dayes ◽  
Stephen J. Lye
Keyword(s):  
Adrenergic Receptors ◽  
Contractile Activity ◽  
Significant Inhibition ◽  
Scatchard Analysis ◽  
Continuous Exposure ◽  
Partial Recovery ◽  
Adrenergic Agonists ◽  
Camp Content ◽  
Adrenoceptor Antagonist ◽  
Β Adrenergic Receptors

Continuous exposure of ovine myometrial strips exposed to isoproterenol (10 μM) resulted in only transient inhibition with contractions returning within 60 min. Rechallenging these strips with isoproterenol failed to induce inhibition, confirming the occurrence of desensitization. In contrast, exposure of myometrial tissue to isoproterenol for only 5 min did not result in desensitization. Myometrial strips exposed to isoproterenol demonstrated a significant increase in cAMP content associated with inhibition of contractile activity and a subsequent fall in cAMP content upon desensitization. Elevation of endogenous cAMP levels by either inhibition of cAMP-dependent phosphodiesterase activity (0.5 mM isobutylmethylxanthine, in ovine strips) or direct activation of adenylyl cyclase (10 μM forskolin, in rat strips) induced a rapid and significant inhibition of myometrial contractile activity in desensitized tissue. Scatchard analysis of the binding of the β-adrenoceptor antagonist, [125I]iodocyanopindolol, revealed a significant reduction in the concentration of β-adrenergic receptors (but no change in binding affinity) in desensitized myometrial tissue. Incubation of desensitized tissue with fresh buffer for 3 h induced only a partial recovery in responsiveness to isoproterenol. These data suggest that prolonged, but not acute, exposure of the myometrium to β-adrenergic agonists induces a state of desensitization that is associated with a down-regulation of β-adrenoceptors but maintenance of postreceptor function.Key words: myometrium, contraction, β-adrenergic receptors, β-antagonists.

scholarly journals Adrenergic and Cholinergic Receptors of Cerebral Microvessels

1981 ◽  
Vol 1 (3) ◽  
pp. 329-338 ◽  
Author(s):  
Sami I. Harik ◽  
Virendra K. Sharma ◽  
John R. Wetherbee ◽  
Robert H. Warren ◽  
Shailesh P. Banerjee
Keyword(s):  
Adrenergic Receptors ◽  
Specific Binding ◽  
Cholinergic Receptors ◽  
Biologically Active ◽  
Adrenergic Agonists ◽  
Muscarinic Cholinergic Receptors ◽  
Cerebral Microvessels ◽  
Binding Characteristics ◽  
Muscarinic Cholinergic ◽  
Β Adrenergic Receptors

The presence of α- and β-adrenergic and muscarinic cholinergic receptors in cerebral microvessels of the rat and pig was assessed by ligand binding techniques. The results demonstrate the presence of specific binding to α2- and β-adrenergic receptors but no appreciable specific binding to α1-adrenergic or muscarinic cholinergic receptors. β-Adrenergic receptors of pig cerebral microvessels are similar to those of the brain and other organs in their binding characteristics to the tritiated ligand and in their stereospecificity of binding to the biologically active isomers of β-adrenergic agonists. Further evidence derived from the differential potency of binding displacement by the various β-adrenergic agonists and selective β1- and β2-adrenergic antagonists indicates that β-adrenergic receptors of pig cerebral microvessels are mostly of the β2-subtype.

Interaction of β-adrenergic agonists and antagonists with the stimulation of growth hormone release induced by clonidine or by morphine in the rat

1982 ◽  
Vol 94 (3) ◽  
pp. 327-331 ◽  
Author(s):  
M. T. Bluet-Pajot ◽  
D. Durand ◽  
F. Mounier ◽  
C. Schaub ◽  
C. Kordon
Keyword(s):  
Adrenergic Receptors ◽  
Hormone Release ◽  
Adrenergic Agonists ◽  
Adrenergic Agonist ◽  
Basal Secretion ◽  
Experimental Conditions ◽  
Gamma Hydroxybutyrate ◽  
Β Adrenergic Receptors ◽  
Dose Dependent

The β-adrenergic agonist, isoprenaline, and antagonist, propranolol, had no effect on the delayed basal secretion of GH consistently observed in rats treated with the narco-analgesic gamma-hydroxybutyrate. Under the same experimental conditions, GH release was distinctly stimulated by infusion of the α-adrenergic agonist, clonidine, and by morphine; both responses were dose-dependent. The effects of β-adrenergic agonists and antagonists on these GH responses were as follows: in rats pretreated with isoprenaline the GH release induced by clonidine and morphine was abolished whereas it was enhanced in rats pretreated with propranolol. These data confirmed and extended previous reports from this laboratory on the inhibitory role of β-adrenergic receptors on GH regulation.

Evidence for α-adrenergic receptors acting through the guanylate cyclase system in human cultured thyroid cells

1983 ◽  
Vol 104 (1) ◽  
pp. 64-68 ◽  
Author(s):  
Maria Luisa Brandi ◽  
Carlo M. Rotella ◽  
Annalisa Tanini ◽  
Roberto S. Toccafondi
Keyword(s):  
Guanylate Cyclase ◽  
Adrenergic Receptors ◽  
Human Thyroid ◽  
Camp Accumulation ◽  
Adrenergic Agonists ◽  
Adrenergic Agonist ◽  
Thyroid Cells ◽  
Camp Content ◽  
Adrenergic Antagonist ◽  
Camp Levels

Abstract. In order to investigate the presence of α-adrenergic receptors in human thyroid, we have studied the effect of α-adrenergic agonists and antagonists on cGMP cellular content of human thyroid cells in primary culture. Epinephrine as well as TSH were not able to modify the cGMP cellular levels, while norepinephrine significantly increased cGMP accumulation already at 10 nm, a dose inactive on cAMP accumulation. A non selective α-adrenergic antagonist, phentolamine, significantly inhibited cGMP accumulation induced by norepinephrine. Norepinephrine-induced cGMP accumulation was unaffected by prazosin, an α1-adrenergic antagonist, but was abolished by yohimbine, an α2-adrenergic antagonist. Phenylephrine, an α-adrenergic agonist, produced an increase of cellular cGMP levels without modifying cAMP content. In the presence of TSH, the cGMP response to norepinephrine was not modified; however, the increase of cAMP levels was inhibited by norepinephrine at doses inactive on cAMP accumulation, but active on cGMP levels. The present results demonstrate the existence in human thyroid cells of α2-adrenergic receptors, regulating the guanylate cyclase system. It may be postulated that the counter-regulation exerted by α-adrenergic agonists on the response to TSH operates on the TSH-dependent adenylate cyclase.

Potential Noradrenergic Targets for Cognitive Enhancement in Schizophrenia

CNS Spectrums ◽  
2004 ◽  
Vol 9 (5) ◽  
pp. 350-356 ◽  
Author(s):  
Joseph I. Friedman ◽  
Daniel G. Stewart ◽  
Jack M. Gorman
Keyword(s):  
Prefrontal Cortex ◽  
Adrenergic Receptors ◽  
Atypical Antipsychotics ◽  
Cognitive Enhancement ◽  
Cognitive Impairments ◽  
Cognitive Remediation ◽  
Adrenergic Agonists ◽  
Substantial Evidence ◽  
Β Adrenergic Receptors ◽  
Noradrenergic Function

AbstractSubstantial evidence suggests that alterations in noradrenergic function contribute to the cognitive impairments of schizophrenia. Activation of post-junctional α2a-adrenergic receptors in the prefrontal cortex by the α2a-selective agonist guanfacine has demonstrated some preliminary benefit in subjects with schizophrenia treated with atypical antipsychotics. α1-drenergic receptor activity may be less important in mediating the cognitive impairments of schizophrenia, β-adrenergic receptors may serve as another potential target for cognitive remediation in schizophrenia. However, the potential increase in memory consolidation in schizophrenia patients produced by β-adrenergic agonists may be outweighed by the impairment in cognitive flexibility and executive functioning produced by α-adrenergic agonists. Finally, norepinephrine reuptake inhibitors, such as atomoxetine, hold promise as potential cognitive enhancers in schizophrenia because of their ability to indirectly but selectively increase extracellular dopamine concentrations in the prefrontal cortex.

Molecular Docking and Drug Discovery in β-Adrenergic Receptors

2017 ◽  
Vol 24 (39) ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
Adrenergic Receptors ◽  
Β Adrenergic Receptors

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 Role of β-Adrenergic Receptors and Nitric Oxide Signaling in Exercise-Mediated Cardioprotection

Physiology ◽  
2013 ◽  
Vol 28 (4) ◽  
pp. 216-224 ◽  
Author(s):  
John W. Calvert ◽  
David J. Lefer
Keyword(s):  
Nitric Oxide ◽  
Risk Factors ◽  
Adrenergic Receptors ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nitric Oxide Signaling ◽  
Factors Associated ◽  
Cardioprotective Effects ◽  
Β Adrenergic Receptors

Exercise promotes cardioprotection in both humans and animals not only by reducing risk factors associated with cardiovascular disease but by reducing myocardial infarction and improving survival following ischemia. This article will define the role that nitric oxide and β-adrenergic receptors play in mediating the cardioprotective effects of exercise in the setting of ischemia-reperfusion injury.

Chronic Effects of Metoprolol on Myocardial β-Adrenergic Receptors in Doxorubicin-Induced Cardiac Damage in Rats

1991 ◽  
Vol 17 (4) ◽  
pp. 656-661 ◽  
Author(s):  
Naoya Fujita ◽  
Michiaki Hiroe ◽  
Yotihiko Ohta ◽  
Toshinobu Horie ◽  
Saichi Hosoda
Keyword(s):  
Adrenergic Receptors ◽  
Cardiac Damage ◽  
Chronic Effects ◽  
Β Adrenergic Receptors
Sign in / Sign up

Export Citation Format

Share Document