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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although processes involved in mRNA degradation play a significant role in dictating steady state mRNA levels, the influence of cell surface signaling on mRNA stability control is understood incompletely. In this study, the effects of cAMP-elevating agents on type I angiotensin II receptor (AT1-R) mRNA levels were assessed in cultured rat aortic vascular smooth muscle cells (VSMCs). AT1-R mRNA levels are rapidly reduced by forskolin treatment, in which the maximal effect yields an 80% reduction in AT1-R mRNA levels after 6 hr of treatment. The rate of AT1-R mRNA decay in response to forskolin is greater than its apparent intrinsic decay, as assessed in the presence of the transcriptional inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, suggesting forskolin treatment destabilizes the AT1-R mRNA. Nuclear run-on analysis indicates forskolin treatment does not affect transcription of the AT1-R gene in VSMCs, implying induced AT1-R mRNA destabilization accounts for the entire effect of forskolin in decreasing AT1-R mRNA levels. Dose-effect studies that assessed AT1-R mRNA levels and cAMP production were conducted using forskolin and the beta-adrenergic receptor agonist isoproterenol as agonists. Isoproterenol is almost 3 orders of magnitude more potent at eliciting the reduction in AT1-receptor mRNA levels than it is at stimulating cAMP production. Similarly, forskolin elicits reductions in AT1-R mRNA, which occur at concentrations that fail to elicit a detectable production of cAMP. However, protein kinase A activity is stimulated maximally by isoproterenol and forskolin concentrations that do not stimulate detectable cAMP production. These data provide evidence that the mechanism for down-regulation of AT1-R mRNA levels by cAMP-elevating agents in VSMCs occurs via a PKA-regulated mRNA destabilization pathway.
Mol Pharmacol 1997 Nov
PMID:The vascular smooth muscle type I angiotensin II receptor mRNA is destabilized by cyclic AMP-elevating agents. 935 68

Since various secretory stimuli regulate not only secretion but also protein, RNA, and DNA syntheses in salivary glands, we evaluated the effect of secretory stimuli on the phosphorylation state of CREB (cAMP response element-binding protein). Isoproterenol, forskolin, and CPS-cAMP markedly stimulated the phosphorylation of CREB in parotid acinar cells, and PKA inhibitors H-8 and H-89 dose-dependently inhibited it. In contrast, carbachol (CCH) and A23187 decreased CREB phosphorylation, but CCH did not decrease it in the absence of extracellular Ca2+. Although protein phosphatase inhibitor calyculin A alone markedly increased the phosphorylation, it could not prevent CCH-induced dephosphorylation of CREB. CaM kinase IV, a putative protein kinase for CREB in response to Ca2+ elevation, was undetectable in parotid acinar cells.
Biochem Mol Biol Int 1997 Oct
PMID:Regulation of CREB phosphorylation by cAMP and Ca2+ in parotid acinar cells. 935 75

The purpose of this study was to test the relationship between biochemical and functional changes accompanying beta-agonist induced cardiac hypertrophy and the activation of a calcium stimulated cysteine protease. Because the ultrastructural and ionic changes accompanying beta-agonist induced cardiac hypertrophy are reminiscent of the actions of the calcium activated neutral protease, calpain, it was hypothesized that lowering calpain activity (by the use of an exogenous inhibitor(s)) would reduce the extent of hypertrophy. Rats (275-300 g) were randomly assigned to either a control, beta-agonist (iso) or cysteine protease inhibitor (E64c) group. Isoproterenol administration (1 mg/kg) resulted in changes for ventricular weight to body weight ratio (increases 19%), ventricular [RNA] (increases 105.6%), rate of pressure development (increases 22% for +dP/dt) and maximum developed left ventricular pressure (increases 19%) (p < 0.05) after 3 days. Calpain-like activity (assessed by microplate method) increased by 45% (p < 0.05), while [cAMP] returned to control levels (following a transient rise at 1 day; 606.03 +/- 124.1 pmol/g/wet/wt to 937.9 +/- 225 (p < 0.05)). E64c (administered 1 h prior to iso) reduced the extent of hypertrophy, from 19 to 12%, and prevented the increases in; total [RNA], left ventricular function, the initial [cAMP] increase and calpain-like activity. It is concluded that a calcium stimulated cysteine protease(s), such as calpain, may be involved in the biochemical and functional changes associated with isoproterenol induced cardiac hypertrophy.
Mol Cell Biochem 1997 Nov
PMID:A calcium stimulated cysteine protease involved in isoproterenol induced cardiac hypertrophy. 940 68

The contribution of adrenergic stimulation to the proarrhythmic effects of pinacidil (30 microM), an opener of ATP-sensitive potassium channels (K+ATP), was tested in an isolated guinea-pig heart model of global ischemia (10 min) and reperfusion (10 min). None (0%) of the control hearts (n=10) elicited arrhythmias during ischemia or reperfusion. In the pinacidil-treated group, one heart (5%) experienced episodes of ventricular tachycardia (VT)/fibrillation (VF) during normoxia. During ischemia, 63% (12 out of 19) of pinacidil-treated hearts exhibited episodes of VT or VF. Hearts not in VT or VF (n=7) at the time of reperfusion, exhibited 71% VT and 43% VT/VF upon reperfusion. Proarrhythmic effects of pinacidil during ischemia or reperfusion were completely reversed by glyburide (n=9; 10 microM), a K+ATP antagonist, or nadolol (n=9; 3 microM), a beta-adrenergic antagonist. Isoproterenol (n=10; 50 nM), a beta-adrenergic agonist, induced a 20% incidence of ischemic VT and VF, and a 70% incidence of reperfusion VF, while methoxamine (n=10; 10 microM), an alpha-adrenergic agonist, demonstrated little proarrhythmia (20% VT/VF at reperfusion only). Proarrhythmic effects of isoproterenol were reversed by nadolol, but not glyburide. Pinacidil caused a slight potentiation of tachycardia induced by a bolus injection of tyramine (30 micro g), an indirectly acting sympathomimetic, but bolus injections of pinacidil (100 micro g) had no effect on heart rate. Nisoxetine, a catecholamine uptake 1 inhibitor, had no proarrhythmic effects when given alone. Catecholamine levels were reduced in pinacidil-treated hearts relative to vehicle-treated. In conclusion, it is suggested that the proarrhythmic effects of pinacidil following global ischemia and reperfusion in the isolated perfused guinea-pig heart appears to involve stimulation of beta-adrenoceptors. These proarrhythmic effects of pinacidil do not appear to be mediated solely through direct opening of K+ATP, but rather through an indirect enhancement of catecholamine release.
J Mol Cell Cardiol 1998 Feb
PMID:Proarrhythmic effects of pinacidil are partially mediated through enhancement of catecholamine release in isolated perfused guinea-pig hearts. 951 18

The nona-peptide oxytocin (OT) induces contraction of the myometrium by interaction with specific plasma membrane associated OT receptors (OTR), whereas stimulation of beta2-adrenoceptors (beta2AR) causes relaxation. Homologous desensitization of the myometrium to both hormones has been described. However, a possible interaction between the two systems has not been investigated. In the present study, long-term in vivo treatment of non-pregnant estrogen-primed rats with isoproterenol decreased maximal relaxation of isolated uterine strips challenged with isoproterenol. Increased EC50 values of similarly treated animals suggest that the coupling between receptor occupancy and contractile response was impaired. Since beta2AR mRNA levels were left unchanged, we conclude that the homologous desensitization to beta2 stimulation is not due to changes in beta2AR gene expression. OT infusion did not alter beta2AR mRNA levels or isoproterenol-induced relaxation of isolated uterine strips. Treatment with OT had no effect on the amount of myometrial OTR mRNA. We have previously found that OT down-regulates OTR in the non-pregnant rat myometrium, but this therefore does not appear to take place at the level of mRNA production. Isoproterenol treatment resulted in a three-fold increase in OTR mRNA. This was accompanied by a 91% rise in OTR binding and an augmented contractile response of isolated uterine strips to OT, suggesting that the increased production of mRNA reflects formation of active receptors. Neither OTR affinity nor EC50 of in vitro strips was affected by isoproterenol treatment. We conclude that stimulation of beta2AR causes heterologous up-regulation of OTR in the non-pregnant estrogen-primed rat myometrium.
J Mol Endocrinol 1998 Apr
PMID:Beta2-adrenoceptor desensitization in non-pregnant estrogen-primed rat myometrium involves modulation of oxytocin receptor gene expression. 958 40

We have used rat cortical astrocytes in culture to investigate the signaling pathways involved in the regulation of fibroblast growth factor-2 (FGF-2) and one of its high affinity receptor FGF receptor-1 (FGFR-1). These cells represent a source of different neurotrophic factors and play important roles in physiological and pathological conditions of the central nervous system. FGF-2 mRNA levels are increased by stimulation of beta-adrenergic receptors or exposure to glucocorticoid hormones and these effects are additive to each other. The regulation of FGFR-1, highly expressed in cultured astroglial cells, appears to be different. Isoproterenol produced an elevation of FGFR-1 mRNA levels, whereas dexamethasone decreased its expression alone or in the presence of isoproterenol, suggesting that the glucocorticoid pathway may predominate over the cAMP-induced up-regulation of the receptor. FGF-2 over-expression may produce different cellular responses depending on the concomitant regulation of its receptor and the cell phenotype where these changes do occur. These mechanisms can contribute to adaptive changes taking place in the CNS in different physiological and pathological situations.
Brain Res Mol Brain Res 1998 Jun 01
PMID:Differential regulation of FGF-2 and FGFR-1 in rat cortical astrocytes by dexamethasone and isoproterenol. 963 May 2

We report the initial characterization of [3H]5-(N-methyl-N-isobutyl)amiloride (MIA) binding to the Na+/H+ exchanger (NHE) and expression of its gene in mammalian cerebrovascular, choroidal and neocortical tissues. [3H]MIA bound reversibly to particulate fractions of rat, pig and human cerebral microvessels, choroid plexus and cerebral cortex. Scatchard analyses revealed binding to a single amiloride-sensitive site with dissociation constants (Kd) ranging from 20 to 90 nM for the various tissue preparations. The maximal binding capacities (Bmax) were between 2 to 17 pmol/mg protein and were several-fold greater in cerebral microvessels compared to the cerebral cortex. Amiloride, MIA, 5-(N, N-hexamethylene)amiloride (HMA), 5-(N, N-dimethyl)amiloride (DMA) and 5-(N-methyl-N-isopropyl)amiloride (IPA) variably displaced [3H]MIA binding to the microvessels in the following rank order: MIA>HMA>/=IPA>DMA>amiloride. Benzamil, a potent ligand of the Na+/Ca+ transporter was the least sensitive. These binding results were most compatible with the existence of the amiloride-sensitive NHE type 1 in the brain vascular and choroidal tissues. To substantiate this, we utilized reverse transcription polymerase chain reaction (RT-PCR) techniques to search for NHE-1 mRNA. Using primers corresponding to conserved sequences of the human growth factor-activatable NHE gene, RT-PCR revealed strong expression of NHE-1 mRNA in cerebral microvessels, choroid plexus, pial vessels and vascular smooth muscle cells relative to neocortical tissues from several species including rat, pig, cow, monkey and human subjects. Further confirmation of NHE-1 isoform mRNA expression in the cerebrovascular tissues was obtained by HpaII restriction digestion analysis and by subcloning and sequencing of the PCR amplified products. Our study suggests that mammalian cerebrovascular and choroidal tissues contain high amounts of the ubiquitous amiloride-sensitive [3H]MIA binding proteins consistent with the expression of NHE type 1 mRNA.
Brain Res Mol Brain Res 1998 Jul 15
PMID:Identification and expression of the Na+/H+ exchanger in mammalian cerebrovascular and choroidal tissues: characterization by amiloride-sensitive [3H]MIA binding and RT-PCR analysis. 968 33

Phospholamban gene transcript levels are much lower in murine atria as compared to murine ventricles and this reduced phospholamban expression has been suggested to result in enhanced atrial contractile parameters. To delineate the functional role of phospholamban in murine atrium, the contractile parameters of isolated muscles from phospholamban knockout and cardiac-specific phospholamban overexpression mice along with their isogenic wild-type controls were evaluated. Assessment of the times (ms) to peak tension development and to half-relaxation of developed tension, as well as the rates (mg/s) of tension development and relaxation in paced atrial muscles, revealed that phospholamban ablation was associated with enhanced rates of relaxation with no significant effect on contraction rate, while phospholamban overexpression (three-fold) was associated with depressed rates of both contraction and relaxation. Isoproterenol stimulation resulted in significant increases in the rates of developed tension and relaxation in both phospholamban deficient and phospholamban overexpression atria, indicating that the beta-adrenergic pathway was functional in these muscles. These findings suggest that phospholamban is an important modulator of atrial contractility and its responses to beta-adrenergic agonists.
J Mol Cell Cardiol 1998 Jul
PMID:Phospholamban modulates murine atrial contractile parameters and responses to beta-adrenergic agonists. 971 Jul 96

Adrenergic stimulation of parotid secretion was investigated in anaesthetised brushtail possums to ascertain fluid secretion rates and salivary composition. Because neither alpha- nor beta-adrenergic stimulation evoked saliva output, infusion of the adrenergic agonists was superimposed on a pre-existing bethanechol-stimulated flow. Isoprenaline infusion (2.4 nmol min-1) increased salivary amylase activity, [protein]; [HCO3]; [PO4] and [Ca], and amylase/Ca and protein/Ca ratios; reduced [Cl]; [K] and osmolality; but did not alter H+ activity; [urea]; [Na]; [Mg]; amylase/protein or saliva/plasma urea ratios. These data are consistent with isoprenaline stimulating acinar secretion of protein, Ca and PO4 but not the ion transport necessary for primary fluid formation at the endpieces and modifying transport of monovalent ions in the excurrent ducts. Consequently, the possum parotid has beta-adrenergic receptors in both the endpieces and excurrent ducts. Phenylephrine infusions at 2.4 and 24 nmol min-1 were without effect whereas phenylephrine at 240 nmol min-1 caused changes in salivary composition which paralleled those for isoprenaline administration but were generally of lesser magnitude. Thus, the possum parotid has few or no alpha-adrenergic receptors and the salivary response elicited was the result of cross-reaction of phenylephrine with beta-adrenergic receptors.
Comp Biochem Physiol A Mol Integr Physiol 1998 Jun
PMID:Response of the parotid gland of the brushtail possum, Trichosurus vulpecula, to adrenergic stimulation. 977 9

A dual approach was employed to study beta-adrenergic receptor signal transduction in post ischemic (stunned) myocardium, examining physiological interventions in awake, chronically instrumented pigs and biochemical, cellular mechanisms in sarcolemmal preparations from the stunned hearts using the contralateral non-ischemic zone as a control. Ten min of coronary artery occlusion (CAO) and 30 min coronary artery reperfusion (CAR) resulted in depressed posterior wall-thickening (myocardial stunning). Isoproterenol increased transmural wall thickening more in stunned myocardium than in non-ischemic myocardium. In contrast, the responses of wall thickening to forskolin, actually decreased during stunning compared with control. NKH 477, a water soluble forskolin derivative, that does not activate cardiac nerves, increased wall thickening in non-ischemic tissue similarly to the effects on stunned myocardium. Increasing cardiac neural tone reflexly with inferior venal caval occlusion (IVCO) elicited similar results to forskolin, i.e., stunned myocardium responded with less of an increase in wall thickening as compared with non-ischemic myocardium. Beta-adrenergic receptor density, as determined with 125I-cyanopindolol binding, was significantly increased in stunned subendocardium and subepicardium compared with respective values in non-ischemic myocardium. There were no differences in the response of adenylyl cyclase to isoproterenol in stunned and non-ischemic myocardium. The enhanced responsiveness of the beta-adrenergic receptor to isoproterenol stimulation in stunned myocardium corresponded to the increase in beta-adrenergic receptor density. The combination of enhanced responses to isoproterenol, and decreased responses to forskolin and to IVCO and preserved responsiveness to NKH 477, suggest that stunned myocardium is characterized by transient sympathetic neural stunning. The enhanced sensitivity to beta-adrenergic receptor stimulation has important clinical implications, both in terms of therapy of stunned myocardium and detection of stunned and/or hibernating myocardium, i.e., low dose dobutamine echocardiography.
Mol Cell Biochem 1998 Sep
PMID:Physiological and biochemical adrenergic regulation of the stunned myocardium. 977 94


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