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

The actions of cyclic AMP are subject to several levels of post-receptor modulation in cardiac tissue. Isoproterenol and prostaglandin E1 both stimulate cAMP accumulation, but only isoproterenol causes activation of particulate cAMP-dependent protein kinase, leading to activation of phosphorylase kinase and glycogen phosphorylase, and inhibition of glycogen synthase. Through the use of isolated, adult ventricular myocytes, we have determined that the hormone-specific activation of glycogen phosphorylase is due to subcellular compartmentation of cAMP. There is some evidence that cyclic nucleotide phosphodiesterases, whose activity is stimulated by alpha 1-adrenergic agonists in isolated myocytes, may have a role in compartmentation. Phosphoinositide hydrolysis is stimulated by alpha 1 and muscarinic agonists, presumably leading to activation of protein kinase C, which in turn has multiple effects on hormone-sensitive adenylate cyclase.
Mol Cell Biochem
PMID:Post-receptor modulation of the effects of cyclic AMP in isolated cardiac myocytes. 284 10

The beta-adrenergic agonist 1-isoproterenol induced an early (less than 1 min) stimulation of endocytosis, amino acid transport and hexose transport, monitored by the temperature-sensitive uptake of horseradish peroxidase, alpha-aminoisobutyrate and 2-deoxyglucose, respectively, in rat ventricle cubes. This stimulation was time- and concentration-dependent and was maximum at 10(-8) M isoproterenol. The beta-adrenergic antagonist propranolol blocked isoproterenol stimulation of membrane transport, thereby confirming beta-adrenoceptor mediation; 2.5 mM EGTA, 1 mM LaCl2 and 100 microM verapamil blocked the hormonal response without affecting basal transport. The calcium ionophore A23187 caused an acute stimulation of endocytosis, hexose and amino acid transport. Isoproterenol rapidly (less than 30 s) stimulated 45Ca2+ influx. These data suggest that stimulus-response (stimulus-"transport") coupling is mediated by a rise in cytosolic Ca2+ concentration. A rapid (less than 30 to 60 s) increase in ornithine decarboxylase (ODC) activity, followed by an early (less than 1 to 2 min), sustained increase in putrescine, spermidine and spermine concentrations was evoked by 10(-7) M isoproterenol. The ODC inhibitor alpha-difluoromethylornithine (DFMO, 5 mM) suppressed the isoproterenol-induced increase in ODC and polyamine levels and the stimulation of 45Ca influx, endocytosis, hexose transport, and amino acid transport. Putrescine (0.5 mM) negated DFMO inhibition and restored the increase in polyamines, 45Ca influx, endocytosis, and transport of hexose and amino acid. These data suggest that polyamine synthesis is involved in isoproterenol stimulation of Ca2+ influx and membrane transport functions in ventricular myocardium. These findings are consistent with a model for signal transduction and stimulus-response coupling in which polyamines function as intracellular messengers to generate cytosolic Ca2+ signals by stimulating Ca2+ influx.
J Mol Cell Cardiol 1988 Sep
PMID:The role of polyamines in beta-adrenergic stimulation of calcium influx and membrane transport in rat heart. 285 23

Primary cultures of myocardial cells from neonatal rats were exposed for up to 5 days to the cyclic AMP derivative 8-Br-cAMP. After one day of exposure to the nucleotide, an increase in specific binding capacity of the hydrophilic beta-adrenoceptor antagonist 3H-CGP 12177 was observed in intact cells. (-)-Isoprenaline displaced the radioligand from its binding site. Neither the KD of the antagonist, nor that of the agonist were significantly affected by 8-Br-cAMP. The loss of beta-adrenoceptors during desensitization by long term treatment of the cells with isoprenaline could be partially prevented by 8-Br-cAMP. Only in desensitized, but not in normal cells was isoprenaline-induced cAMP formation significantly enhanced by 8-Br-cAMP pretreatment. This may indicate that beta-adrenoceptors which appear during 8-Br-cAMP exposure are poorly coupled to the adenylate cyclase. Alternatively, the change in receptor density may be accompanied by alterations of other components in the beta-adrenergic system, e.g. an inhibition of the adenylate cyclase. We suggest that cAMP-dependent feed-back regulation of the beta-adrenergic system may play a role during postnatal myocardial differentiation.
J Mol Cell Cardiol 1985 Apr
PMID:Regulation by 8-Br-cAMP of beta-adrenoceptors in cultured myocardial cells. 286 85

Basal levels of cyclic adenosine monophosphate (cAMP) were measured in embryonic chick hearts at various times during development. Basal cAMP was highest on incubation day 5 and decreased throughout the remaining incubation period. Cyclic AMP could not be stimulated above basal level by intravenous in ovo administration of isoproterenol or tyramine on incubation day 5; however, there was a decrease in cAMP 2 mins after intravenous injection which was identical to the decrease in cAMP in controls injected with saline. Heart rate decreased following intravenous injection of saline on incubation day 5, but a similar decrease was not observed following intravenous isoproterenol injection. Functional sympathetic innervation of the heart does not occur until incubation day 16, and this fact is responsible for the insensitivity to tyramine stimulation on incubation day 5. Although the level of cAMP could not be stimulated above basal level on incubation day 5, beta-antagonists caused a decrease in the level of cAMP, with no decrease in heart rate. These observations indicate that the beta-receptor is coupled to adenylate cyclase on incubation day 5 but it is questionable whether adenylate cyclase is effectively coupled to heart rate. Isoproterenol and tyramine caused a significant elevation in cardiac cAMP and heart rate on incubation day 17 following intravenous in ovo injection. Hearts made sympathetically aneural by removal of premigratory neural crest responded to isoproterenol but not tyramine on incubation day 17 which demonstrates that the morphologically aneural hearts are also functionally aneural.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1986 Aug
PMID:Cyclic AMP in normal and sympathetically aneural chick hearts during development. 287 90

Isoproterenol-induced myocardial necrosis was examined in male mice with alloxan-induced and genetically transmitted diabetes. Ten days after alloxan treatment, mice exhibited an elevation in blood glucose concentrations, weight loss, polyuria and decreased heart rates (510 +/- 15 v. 675 +/- 11 beats/min) compared with matched control mice. Similarly, genetically diabetic mice exhibited lower heart rates than the corresponding age-matched controls (383 +/- 30 v. 603 +/- 30 beats/min). In comparison to matched controls, both groups of diabetic mice had a significant decrease in the severity of the cardiac necrosis which was induced by the administration of isoproterenol. The reduction in isoproterenol-induced cardiac lesions was similar in mice with chemically induced diabetics and mice with genetically transmitted diabetes. Biochemical studies of ventricular slices revealed no change in basal cAMP levels and no differences in isoproterenol-induced changes in cAMP levels in mouse hearts from both models of diabetes. Insulin treatment corrected the chemically induced diabetic state and restored the cardiotoxic potential of isoproterenol.
J Mol Cell Cardiol 1985 Apr
PMID:Influence of the diabetic state on isoproterenol-induced cardiac necrosis. 299 38

The effect of GDP on rabbit heart adenylate cyclase has been determined under conditions where only 0.08% to 0.26% of an added 100 microM was converted to GTP in the course of the assay. At concentrations of 100 microM, GDP stimulated basal cyclase activity to the same extent as GTP and guanosine-5'-O-(2-thiodiphosphate) (GDP beta S). Isoproterenol increased activity in the presence of GTP or guanylyl-imidodiphosphate (Gpp(NH)p), but not in the presence of GDP or GDP beta S. It is suggested that the hydrolysis of GTP to GDP is the "turn-off" mechanism for beta-receptor stimulation of cardiac adenylate cyclase, but not for stimulation by GTP alone. The effects of GDP and GDP beta S are readily removed by washing, implying that their binding to Ns (the guanine nucleotide binding protein) is weak. GDP beta S initially competes with Gpp(NH)p, reducing Gpp(NH)p-stimulated activity. As stimulation of cyclase activity by Gpp(NH)p develops, in the course of 30 min, Gpp(NH)p becomes no longer displaceable by GDP beta S. Isoproterenol does not release 3H-Gpp(NH)p or reduce Gpp(NH)p-stimulated activity, once the nucleotide has become tightly bound. Nor does isoproterenol change the relative affinities of GDP beta S and Gpp(NH)p when these analogs are given together. There is, therefore, no evidence that isoproterenol acts by releasing tightly bound GDP from Ns, or that it 'unlocks' the guanine nucleotide binding site in the myocardial sarcolemma. In this, the cardiac adenylate cyclase system differs from the avian erythrocyte system. The action of isoproterenol is best explained by an increased dissociation of alpha(GTP) and beta,gamma-subunits of the Ns protein.
J Mol Cell Cardiol 1986 Aug
PMID:GDP activates rabbit heart adenylate cyclase, but does not support stimulation by isoproterenol: a re-appraisal of the control mechanism. 301 66

Isoproterenol (50 nM) potentiated the effects of angiotensin (1-50 nM) on 86Rb efflux and 45Ca efflux from guinea pig hepatocytes. This effect occurred in the presence or absence of extracellular Ca2+ and required the simultaneous presence of both isoproterenol and angiotensin. Neither the divalent cationophore, A23187, nor 4 beta-phorbol dibutyrate could substitute for angiotensin. The effects of isoproterenol were greatest with submaximal concentrations of angiotensin, whereas maximal concentrations of angiotensin were affected little. Isoproterenol did not substantially increase the formation of [3H]inositol triphosphate or the ratio of isomers [3H]inositol 1,4,5-trisphosphate and [3H]inositol 1,3,4-trisphosphate formed in response to angiotensin. Isoproterenol also enhanced the phase of Ca2+ mobilization involving Ca2+ entry which is consistent with the previously proposed functional linkage between receptor-regulated Ca2+ release and Ca2+ entry. These findings suggest that isoproterenol may act by increasing the sensitivity of the endoplasmic reticulum to the Ca2+-releasing action of inositol 1,4,5-trisphosphate.
Mol Pharmacol 1986 Oct
PMID:Further studies on the interactions between the calcium mobilization and cyclic AMP pathways in guinea pig hepatocytes. 302 Mar 89

Isoproterenol (IPR), a beta-adrenergic agonist, induces division of acinar cells in the parotid and submandibular glands of adult rodents and produces hyperplastic and hypertrophic enlargements of these organs. We analyzed the effects of IPR on thymidine incorporation, c-fos mRNA levels, and the immunocytochemical localization of c-fos protein in the submandibular glands of adult and of 5- and 14-day-old mice. In the glands of untreated mice c-fos transcripts were not detectable. In all experimental groups, administration of IPR led to a rapid, transient increase in the c-fos mRNA level. Propranolol blocked the IPR effect, while treatment with IPR and cycloheximide led to superinduction. We observed no correlation between the effect of IPR on cell replication or organ growth and stimulation of c-fos expression, and conclude that the latter is the result of beta-adrenergic receptor-IPR interaction. The c-fos protein was localized immunocytochemically in both the cytoplasm and the nuclei of acinar cells and in the nuclei of duct cells.
Mol Cell Biol 1986 Aug
PMID:Beta-adrenergic stimulation of c-fos gene expression in the mouse submandibular gland. 302 55

Parathyroid hormone (PTH), the plasma concentration of which is raised in uremia, has been suggested as one of the agents responsible for the myocardial changes commonly seen in uremia. The effect of intact PTH on rat heart cells grown in tissue culture has been studied. Addition of the hormone to the media significantly stimulated beating rate. The stimulation was directly proportional to the amount of PTH in the medium. Excessively high concentration of PTH caused immediate cessation of the beating, which was reversed by the addition of calcium to the medium. The extent of stimulation by PTH was inversely proportional to the calcium concentrations in the medium. Isoproterenol and phenylephrine at excessively high concentrations in the medium did not mimic the PTH effect either alone or together with PTH. When beating ceased due to verapamil the effect was not reversed by the addition of calcium to the medium. Calcium added to the myocytes seen after beating ceased reversed the effect and the cells started to beat again. Cells kept for a longer period in the arrested state were not revived by the addition of calcium.
Mol Cell Biochem 1987 Sep
PMID:The relationship of calcium and parathyroid hormone in their effect on heart cells. 312 19

Impaired energy production has been proposed as one mechanism to explain the contractile abnormality in post-ischemic "stunned" myocardium. If energy production were impaired, administration of inotropic agents should result in a deterioration of cellular energy stores because of an inability of ATP synthesis to match the rate of increased utilization. In this study we correlated changes in myocardial high energy phosphates, measured by 31P-NMR spectroscopy, with changes in left ventricular function and energy requirement in buffer perfused rabbit hearts following ischemia and reperfusion, and during stimulation with isoproterenol. Hearts were stunned by 20 min of zero flow global ischemia at room temperature. After reperfusion, isovolumic developed pressure returned to 77.8 +/- 2.2% of baseline and ATP content was reduced to 80.9 +/- 4.1% of baseline. Isoproterenol (5 x 10(-8) M for 10 min) caused increases in developed pressure and rate-pressure product (to 134.1 +/- 12.6% and 195.0 +/- 21.4% of baseline, respectively) without a decrease in ATP or phosphocreatine (PCr) content (80.0 +/- 7.1% and 103.0 +/- 3.8% of preischemia, respectively), and without functional or metabolic deterioration of the hearts after discontinuation of the drug. Control hearts not subjected to ischemia showed similar functional and metabolic responses to isoproterenol. The phosphocreatine/inorganic phosphate (PCr/Pi) ratio, an index of the balance between energy production and utilization, was higher (not lower) than baseline in stunned hearts, thus confirming that energy production was not intrinsically impaired. Together these data indicate that despite reduced myocardial ATP content, mitochondrial function in stunned hearts is capable of sustaining a large increase in function and energetic requirements.
J Mol Cell Cardiol 1987 Oct
PMID:Preserved high energy phosphate metabolic reserve in globally "stunned" hearts despite reduction of basal ATP content and contractility. 343 54


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