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Adrenergic Pathways (adrenergic + pathway)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

An abnormal gene expression of the ,-adrenergic system contributes to the pathogenesis of cardiomyopathy in cirrhotic rats,

HEPATOLOGY, Issue 6 2008
Giulio Ceolotto
Decreased cardiac contractility and ,-adrenergic responsiveness have been observed in cirrhotic cardiomyopathy, but their molecular mechanisms remain unclear. To study ,-adrenergic,stimulated contractility and ,-adrenergic gene expression patterns, 20 Wistar Kyoto rats were treated with carbon tetrachloride to induce cirrhosis and 20 rats were used as controls. Left ventricular contractility was recorded in electrically driven isolated hearts perfused at constant flow with isoproterenol (10,10 to 10,6 M). A cardiac gene expression profile was obtained using a microarray for the myocyte adrenergic pathway. The cardiac contractility maximal response to isoproterenol was significantly reduced in cirrhotic rats in comparison to control rats, whereas the half-maximal effective concentration was not different. In cirrhotic rats, cardiac gene expression analysis showed a significant overexpression of G protein alpha,inhibiting subunit 2 (G,i2), cyclic nucleotide phosphodiesterase (PDE2a), regulator of G-protein signaling 2 (RGS2), and down-expression of adenylate cyclase (Adcy3). These results indicate that overexpression of G,i2, PDE2a, and RGS2 down-regulates the ,-adrenergic signaling pathway, thus contributing to the pathogenesis of cirrhotic cardiomyopathy. (HEPATOLOGY 2008;48:1913-1923.) [source]

Clinical and experimental aspects of Adreno-muscarinic synergy in the bladder base and prostate,,

NEUROUROLOGY AND URODYNAMICS, Issue 8 2009
Alexander Roosen
Abstract Recent clinical trials have shown that combination therapy using an alpha-receptor antagonist and an antimuscarinic is more effective than either agent alone in improving quality of life and objective urodynamic variables in men with bladder outflow obstruction. There appear to be no negative effects on bladder function. The mode of action of this combination is unknown but presumed to be an antimuscarinic reduction in detrusor overactivity and the alpha-receptor antagonist reduced outflow tract resistance. We have shown with in vitro experiments that in smooth muscles influencing outflow tract resistance (prostate, trigone) there is a profound contractile synergy between adrenergic and muscarinic pathways. We propose the hypothesis that both arms of the combination therapy reduce contractile tone of the outflow tract and that their simultaneous attenuation has a disproportionately large effect on outflow tract resistance. Our data from trigone muscle suggest that adrenergic and muscarinic receptor activation increase the intracellular [Ca2+] but the adrenergic pathway also operates through Ca2+ -sensitisation of the contractile apparatus, primarily through a PKC-dependent pathway. Neurourol. Urodynam. 28:938,943, 2009. © 2009 Wiley-Liss, Inc. [source]

Adrenergic regulation of cardiac myocyte apoptosis

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2001
Krishna Singh
The direct effects of catecholamines on cardiac myocytes may contribute to both normal physiologic adaptation and pathologic remodeling, and may be associated with cellular hypertrophy, apoptosis, and alterations in contractile function. Norepinephrine (NE) signals via ,- and ,-adrenergic receptors (AR) that are coupled to G-proteins. Pharmacologic studies of cardiac myocytes in vitro demonstrate that stimulation of ,1 -AR induces apoptosis which is cAMP-dependent and involves the voltage-dependent calcium influx channel. In contrast, stimulation of ,2 -AR exerts an anti-apoptotic effect which appears to be mediated by a pertussis toxin-sensitive G protein. Stimulation of ,1 -AR causes myocyte hypertrophy and may exert an anti-apoptotic action. In transgenic mice, myocardial overexpression of either ,1 -AR or G,s is associated with myocyte apoptosis and the development of dilated cardiomyopathy. Myocardial overexpression of ,2 -AR at low levels results in improved cardiac function, whereas expression at high levels leads to dilated cardiomyopathy. Overexpression of wildtype ,1B -AR does not result in apoptosis, whereas overexpression of G,q results in myocyte hypertrophy and/or apoptosis depending on the level of expression. Differential activation of the members of the mitogen-activated protein kinase (MAPK) superfamily and production of reactive oxygen species appear to play a key role in mediating the actions of adrenergic pathways on myocyte apoptosis and hypertrophy. This review summarizes current knowledge about the molecular and cellular mechanisms involved in the regulation of cardiac myocyte apoptosis via stimulation of adrenergic receptors and their coupled effector pathways. © 2001 Wiley-Liss, Inc. [source]

Effect of in vivo and in vitro ethanol on adrenergic and purinergic responses of the bisected rat vas deferens to low and high frequency pulses

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2001
C. Boselli
1 This study investigates the effect of acute in vivo and in vitro ethanol administration on the contractions evoked electrically and by exogenous noradrenaline and ,,,-methylene-ATP in the rat bisected vas deferens. 2 In vivo ethanol treatment (3 g kg,1, i.p.) significantly potentiated the early purinergic (phase I) and the delayed adrenergic (phase II) phases evoked by single-pulse stimulation of the epididymal portion of the rat vas deferens, leaving unaffected both phases in the prostatic portion. In vitro 50 mM ethanol significantly depressed phase I leaving unaffected phase II in both portions from untreated rats. In vitro ethanol significantly depressed phase I in the epididymal portion from in vivo ethanol treated animals and potentiated phase II in both portions. 3 In vivo ethanol treatment (3.0 g kg,1, i.p.) selectively impaired the response to noradrenaline only in the prostatic portion of rat vas deferens while it was devoid of any action on ,,,-methylene-ATP contractions. Ethanol 50 mMin vitro was devoid of any action on the response to exogenous noradrenaline and ,,,-methylene-ATP in both tissues. 4 In vivo ethanol treatment slightly but significantly increased the phasic response in the epididymal portion to trains of stimuli (2,30 Hz). In vitro 50 mM ethanol was ineffective against the phasic and tonic contractions elicited by the tetanus in both portions. 5 It is concluded that ethanol treatment affects purinergic and adrenergic pathways of transmission possibly leading to a disruption of physiological contractions necessary to seminal emission. [source]

Neural control of the urethra and development of pharmacotherapy for stress urinary incontinence

BJU INTERNATIONAL, Issue 8 2003
M.O. Fraser
SUMMARY This review discusses the control of the urethra by the central nervous system, emphasizing the importance of nervous system control and the role of serotonin and noradrenaline in storage, micturition and sphincter reflexes. The concept of pharmacological neuromodulation and the use of pharmacological therapy as first-line therapy for stress urinary incontinence (SUI) is presented. Coordination between the urinary bladder and urethra is mediated by many reflex pathways organized in the brain and spinal cord. During bladder filling, activation of mechanoreceptor afferent nerves in the bladder wall triggers firing in the cholinergic efferent pathways to the external urethral sphincter and in sympathetic adrenergic pathways to the urethral smooth muscle. These storage reflexes depend on interneuronal circuitry in the spinal cord and are modulated by descending pathways. It would therefore seem that neurotransmission in the central nervous system and periphery may be important in SUI, and moreover that pharmacological agents affecting these neurotransmitter pathways may be used to treat SUI. The central and peripheral mechanisms of action of duloxetine affect serotonin and noradrenaline neurotransmission in ways that may ameliorate the symptoms of SUI. [source]