Disease relevance of Levarterenol

• To determine if this actin iso-mRNA switch during cardiac hypertrophy reflects changes in the transcriptional status of the myocyte nucleus, we quantified the rate of transcription of actin mRNAs and total RNA, using an in vitro run-on transcription assay with nuclei isolated from the cultured myocytes after stimulation with norepinephrine (NE) [1].
• The enhanced renal NE spillover in obesity may have implications for the development of hypertension in this group, whereas the low cardiac sympathetic tone would be expected to be cardioprotective [2].
• Therefore, we sought to determine whether chronic hypoxia could alter NE-stimulated hypertrophy and if so, whether this alteration was related to alpha 1-AR-mediated signaling and alpha 1-AR changes at both the protein and mRNA levels [3].
• It is not known, however, whether hypoxia, a major component of ischemia, has any direct effect on NE-stimulated hypertrophy [3].
• In Purkinje fibers from dogs treated with pertussis toxin, NE no longer induced a CEC-sensitive decrease in automaticity [4].

Psychiatry related information on Levarterenol

• Following a chemical sympathectomy, hyperalgesia was eliminated and injection of NA into the hyperalgesic paw had no effect on pain thresholds [5].
• The results suggest that NA in PPT tonically inhibits REM sleep, possibly by acting on the cholinergic REM-ON neurons, while GABA inhibits the release of NA for REM sleep regulation [6].
• Gene-gene interaction between the monoamine oxidase A gene and solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2 gene in anorexia nervosa (restrictive subtype) [7].
• Furthermore our results demonstrate an additional mechanism by which NA can modulate the excitability of multipolar VLPO neurons which may have important implications for its role in regulating sleep/wakefulness [8].
• Overnight (12-h) urinary cortisol, norepinephrine (NE) and epinephrine (E) were measured in 21 mothers of pediatric cancer survivors with (n = 14) and without PTSD symptoms (n = 7) and in control mothers of healthy children (n = 8) [9].

High impact information on Levarterenol

• MAOA preferentially oxidizes serotonin (5-hydroxytryptamine, or 5-HT) and norepinephrine (NE), whereas MAOB preferentially oxidizes beta-phenylethylamine (PEA) [10].
• Noradrenaline (NA) released from sympathetic nerves acts on alpha 1-adrenoceptors to increase cytosolic Ca2+ and promote smooth muscle contraction [11].
• During guanadrel compared with placebo, plasma NE levels (1.28 +/- 0.09-0.85 +/- 0.06 nM; P = 0.0001) and the extra vascular NE release rate derived from [3H]NE kinetics were lower (7.1 +/- 0.7-4.0 +/- 0.2 nmol/min per m2; P = 0.0004), suggesting suppression of SNS activity [12].
• In contrast, there was no difference in the FABF response to AII (analysis of variance P = 0.81), suggesting that the upregulation observed to NE was homologous [12].
• Preincubation with Con A, 0.5 micrograms/ml, attenuated 1 microM (-)-norepinephrine (NE)-induced downregulation of beta-adrenergic receptors and resulted in a 50% augmentation of cAMP accumulation stimulated by 1 microM NE [13].

Chemical compound and disease context of Levarterenol

• As is the case for the previously reported inhibitory actions of these transmitters on DRG cell calcium channels, we demonstrate that NE and GABA inhibit peptide secretion through activation of alpha-adrenergic and GABAb receptors that are functionally coupled to pertussis toxin (PTX)-sensitive G proteins [14].
• Together, these data indicate that mice genetically endowed with increased SOD activity are protected from 2'-NH2-MPTP-induced toxicity, thereby implicating superoxide radicals in the mechanism of action of a neurotoxin that selectively depletes 5-HT and NE without affecting dopamine [15].
• (3) Anaphylaxis increased NE and E accumulation by 10 and 19 per cent, respectively [16].
• Acute gastric changes in patients with acute stroke. Part 2: gastroendoscopic findings and biochemical observation of urinary noradrenalin, adrenalin, 17-OHCS and serum gastrin [17].
• The concentration-response relationship for L-lactate showed that the NA contracture was relaxed by 50% at approximately 26 mM [18].

Biological context of Levarterenol

• The NE induction was mediated by the beta-adrenergic receptor in high-density cultures (3-4 x 10(6) cells per 60-mm dish), as was induction of hypertrophy, contractility, and endogenous skeletal alpha-actin gene expression [19].
• A DNA region required for NE responsiveness but not for tissue-specific expression was located between base pair -2000 and base pair -1300 [19].
• Factors related to cell communication may influence the pathways mediating NE-regulated gene transcription during cardiac myocyte hypertrophy [19].
• Yohimbine and NIP increased and PRO + EPI and methoxamine decreased NE FSO, without effects on systemic blood pressure, heart rate, or arterial levels of catechols [20].
• NE (0.1 micrograms/kg per minute) also induced a greater effect on LV dP/dt in the three transgenic mice with heart rates held constant compared with three wild-type control mice (65 +/ 8% versus 28 +/- 4%, P < .05) [21].

Anatomical context of Levarterenol

• The EC50 for NE induction of beta-MHC was 40 nM, and pharmacologic experiments indicated alpha 1-adrenergic receptor specificity. alpha-MHC isogene expression was predominant in control myocytes (68% alpha-isoprotein and 60% alpha-iso-mRNA) [22].
• Global indices of sympathetic nervous system (SNS) function such as plasma or urinary norepinephrine (NE) have been unable to define SNS status in obesity [2].
• The maximal force of contraction induced by NE in the presence or absence of endothelium was significantly decreased (p < 0.05) in vitro in mesenteric artery rings from AMD pump dogs compared with saline control dogs [23].
• In contrast, most neonatal Purkinje fibers show an increase in automaticity in response to these concentrations of NE [4].
• The results suggest that alpha 2-adrenoceptors modulate release of NE from vascular sympathetic nerve endings in humans and that the function of these receptors is unchanged during acute changes in junctional NE concentrations [20].

Associations of Levarterenol with other chemical compounds

• When an intermediate amount of alpha 1- versus alpha 2-adrenoceptor tone was first produced with bath-added norepinephrine (NE) in the presence of rauwolscine or prazosin, L-NMMA caused constriction with greater potency and efficacy during alpha 2 than during alpha 1 tone [24].
• The effect of TGF-beta 1 on the NE action was not blocked by propranolol but by prazosin [25].
• Furthermore, two structurally distinct inhibitors of PI3K (wortmannin and LY294002) inhibited NE uptake in intact as well as digitonin-permeabilized PC12 cells, but had no effect on calcium-evoked NE secretion [26].
• In isolated perfused tail arteries of spontaneously hypertensive rats (SHR), the selective alpha 2-adrenergic receptor antagonist idazoxan ( RX781094 ) at low concentrations antagonized vasoconstrictor responses induced by norepinephrine (NE) and low frequency periarterial field stimulation [27].
• CONCLUSIONS: These data replicate our previous studies demonstrating that acute stress elicits NPY release and that this release is positively associated with cortisol and NE release [28].

Gene context of Levarterenol

• The Ca++ chelator bis(2-aminophenoxy)ethane-N-N-N'-N'-tetraacetate (BAPTA) dose dependently abolished NE-stimulated Ca++ responses but not ERK or JNK activation [29].
• We earlier found an association between anorexia nervosa (AN) restrictive subtype (AN-R) and an inserted sequence within the NETpPR, a polymorphic region located in the promoter of the solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2 (SLC6A2) gene [7].
• Some long projection neurons such as the pyramidal, mitral, principal neurons of several cranial nuclei, and presumably monoaminergic cells containing noradrenalin, dopamine, and serotonin, expressed high levels of L1cam [30].
• Endothelin-1 and -3 diminish neuronal NE release through an NO mechanism in rat anterior hypothalamus [31].
• In comparison to NO and HE, increase of NE, GH and ACTH was significantly higher in HO, NE declined significantly in HE before exercise [32].

Analytical, diagnostic and therapeutic context of Levarterenol

• In contrast, beta-MHC expression was equal to alpha-MHC or predominant after treatment with NE (51% beta-isoprotein and 69% beta-iso-mRNA) [22].
• Norepinephrine (NE) was added to the cremaster bath to produce intermediate reductions in diameter of large arterioles and venules (55% and 38% of maximum constriction, respectively) [33].
• Simultaneous intra-arterial infusions of tracer amounts of [3H]NE were used to calculate the extraction rate of NE in the forearm [20].
• MAT2A mRNA and MAT II protein were increased in organ culture by treatment with norepinephrine (NE), the sympathetic neurotransmitter that stimulates the pineal gland at night [34].
• Since this treatment only partially depletes vascular norepinephrine (NE) content, we evaluated the degree of sympathectomy achieved with the 6-HODA treatment and the structural vascular changes in treated and untreated animals [35].

References