Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The long-term effects of sinoaortic denervation on the development of left ventricular hypertrophy (assessed by the measurement of the ratio (R): heart weight/total body weight and LVT: left ventricular thickness), myocardial beta-adrenergic receptivity (measured by [125I]-cyanopindolol binding and adenylate cyclase activity) and plasma catecholamine levels (measured by h.p.l.c.) were investigated in three groups of dogs: normotensive controls (group 1), dogs made hypertensive by sinoaortic denervation and evaluated 1 (group 2) and 18 months (group 3) later. 2. Noradrenaline (NA) and adrenaline (A) plasma levels were 461 +/- 54 and 85 +/- 45 pg ml-1 in controls, 861 +/- 185 and 191 +/- 23 pg ml-1 in group 2 (P less than 0.05). They were normal in group 3 (426 +/- 132 and 110 +/- 16 pg ml-1). 3. R and LVT values were significantly (P less than 0.05) higher in sinoaortic denervated dogs (R = 7.7 +/- 0.1 and 7.8 +/- 0.2; LVT = 13.6 +/- 1.3 and 14.2 +/- 0.9 mm in groups 2 and 3 respectively) than in normotensive dogs (group 1: R = 6.7 +/- 0.1, LVT = 9.3 +/- 0.8 mm). 4. In group 1, the total number of beta-adrenoceptors (Bmax) was 37 +/- 11 and 29 +/- 6 fmol mg-1 protein in the left ventricle (LV) and right auricle (RA) respectively. In group 2, Bmax was significantly lower (10 +/- 3 in LV and 13 +/- 2 fmol mg-1 protein in RA, P less than 0.05) than in group 1. There was no difference between group 1 and group 3 (37 +/- 3 fmol mg-1 prot in LV and 31 +/- 3 fmol mg-1 protein in RA). 5. The percentage of beta 1-adrenoceptors was 82 +/- 4 in LV and 75 +/- 5 in RA in group 1. It was significantly lower (P less than 0.05) in groups 2 (LV: 33 +/- 6 and RA: 33 +/- 5) and 3 (LV: 59 +/- 3 and RA: 55 +/- 4). 6. Basal values of adenylate cyclase activity in LV significantly decreased after sinoaortic denervation.7. These data show that sinoaortic denervation is associated with left ventricular hypertrophy which appears early (1 month) and persists until 18 months despite the normalization of plasma catecholamine levels. The total number of myocardial beta-adrenoceptors is closely related to catecholamine levels but a selective decrease in beta 1-adrenoceptors is observed during cardiac hypertrophy. The fall in basal adenylate cyclase activity suggests that cardiac hypertrophy is associated with an impairment of transmembrane signalling.
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PMID:Myocardial hypertrophy, cardiac beta-adrenoceptors and adenylate cyclase activity during sinoaortic denervation in dogs. 131 24

Previous assessment of beta-adrenoceptor function has shown alterations in essential hypertension (EH). In the present study, we compared lymphocyte beta-adrenoceptor density (Bmax) and adenylate cyclase (AC) activity stimulated by l-isoproterenol, Gpp(NH)p, Gpp(NH)p + l-isoproterenol, and forskolin in 46 patients with EH and in 17 normotensive subjects. The patients with EH were divided into two subgroups, one with left ventricular myocardial mass (LVMM) less than 200 g and the second with LVMM greater than 200 g (according to Teichholz' formula). There were no significant differences in Bmax or in AC activity [basal and stimulated by Gpp(NH)p and forskolin] between the patients and the normotensive subjects. Adenylate cyclase activity stimulated by l-isoproterenol was reduced (% from basal AC) in the patients (P less than .05), and Bmax was increased only in the patients with left ventricular hypertrophy (P less than .05). There were no differences in AC activity between the two patient subgroups, and Bmax and AC activity did not correlate with blood pressure in either the patients or the normotensive subjects. Correlations were found between Bmax and LVMM (r = 0.38, P less than .02) and between Bmax and interventricular septum thickness (r = 0.412, P less than .02) among the patients. Thus, beta-adrenergic-mediated AC sensitivity to catecholamines is reduced in patients with EH and may represent a generalized defect in beta-receptor function in EH. Increased Bmax is likely to characterize more pronounced involvement of the target organs in the pathologic process associated with EH than is a higher blood pressure level.
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PMID:Alteration of beta-adrenoceptor function in hypertensive patients with different degrees of left ventricular hypertrophy. 132 40

The effects of sinoaortic denervation (SAD) on the development of left ventricular hypertrophy (R: heart weight/total body weight; LVT : left ventricular thickness), myocardial beta-adrenergic receptivity ([125I]CYP binding; adenylate cyclase activity) and plasma catecholamine levels (HPLC) were investigated in both normotensive (group 1) and hypertensive dogs evaluated (group 2) 1 and 18 months (group 3) after SAD. Noradrenaline (NA) and adrenaline (A) plasma levels were 461 +/- 54 and 85 +/- 45 pg/ml in controls, 861 +/- 185 and 191 +/- 23 pg/ml in group 2 (P < 0.05) and were normal in group 3 (426 +/- 132 and 110 +/- 16 pg/ml). R and LVT values were higher (p < 0.05) in SAD dogs (R = 7.7 +/- 0.1 and 7.8 +/- 0.2; LVT = 13.6 +/- 1.3 and 14.2 +/- 0.9 mm in groups 2 and 3 respectively) than in group 1 (R = 6.7 +/- 0.1, LVT = 9.3 +/- 0.8 mm). In group 1, the total number of beta-adrenoceptors (beta-AR) was 37 +/- 11 and 29 +/- 6 fmol/mg prot in left ventricule (LV) and right auricle (RA) respectively. Bmax was significantly lower in group 2 (LV: 10 +/- 3; RA: 13 +/- 2 fmol/mg prot, p < 0.05) than in group 1 but was normal in group 3 (LV: 37 +/- 3 and RA: 31 +/- 3 fmol/mg prot).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Beta adrenergic receptors and experimental left ventricular hypertrophy]. 133 53

Recent reports suggested that a complex alteration in beta-receptor function occurs in failing human myocardium. We evaluated beta-receptor-subtype activity in an experimental model of monocrotaline (MCT)-induced cardiomyopathy in the rat. Through pulmonary hypertension, MCT causes right ventricular hypertrophy (RVH), either associated with heart failure or not, beta-Receptor function was evaluated in both failing-hypertrophic and hypertrophic hearts in binding studies with [125I]iodocyanopindolol (ICYP) and by measuring adenylate cyclase (AC) activity. In the right failing ventricle, beta 1- but not beta 2-receptor density was decreased. Lesion-associated modifications in the adenylate cyclase system were also observed: isoproterenol- and guanosine 5' [beta, gamma-imido]triphosphate [Gpp(NH)p]-stimulated cyclic AMP formation was reduced in the right failing ventricle, while the cyclic AMP responses to NaF and forskolin were unchanged. On the other hand, no changes in either beta-receptor density or function were found in hypertrophic ventricles. MCT-induced heart failure in the rat is thus associated with a selective decrease of beta 1-receptor density and function. These results suggest that MCT-induced cardiac failure may be an appropriate model in which to investigate heart insufficiency further.
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PMID:Beta 1- and beta 2-receptors are differentially desensitized in an experimental model of heart failure. 170 9

The aim of this study was to examine the responsiveness of the hypertrophied left ventricle to beta-adrenergic stimulation in a pressure overload model produced by valvular aortic stenosis and characterized by reduced beta-adrenoceptor number. The study was designed to correlate changes in global and regional cardiac work and energetics in response to isoproterenol with adenylate cyclase activity. Eleven anesthetized dogs with left ventricular hypertrophy and 11 controls were studied at rest and during 0.5 and 1.0 micrograms/kg/min isoproterenol infusion. We measured regional work from segment length and force changes with ultrasonic dimension crystals and miniature force gauges in addition to arterial and left ventricular blood pressure and cardiac output. Regional myocardial oxygen consumption was calculated from O2 extraction using microspectrophotometry and blood flow using radioactively labeled microspheres. Adenylate cyclase activity was assayed at baseline and after stimulation with forskolin. Isoproterenol significantly increased heart rate, dP/dtmax, cardiac output, and external work to similar levels in control and hypertrophied animals. Similarly, regional work increased from 463 +/- 115 to 995 +/- 584 g x mm/min for controls and from 392 +/- 156 to 1175 +/- 577 for hypertrophied dogs with high dose isoproterenol. Regional O2 consumption also increased to similar levels (20.3 +/- 14.7 vs 16.2 +/- 6.3 ml O2/min/100 g) in both groups. Adenylate cyclase activity was lower in hypertrophy at baseline (23.9 +/- 7.3 vs 62.9 +/- 14.2 pM/min/mg protein for controls), but was the same as for controls with forskolin stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between adenylate cyclase activity and regional myocardial energetics in experimental left ventricular hypertrophy. 182 46

Reports in the literature have suggested that a complex alteration in beta-receptor pathway takes place in failing human myocardium. The purpose of our study was to evaluate the beta-adrenergic receptor system in an experimental model of heart failure induced by monocrotaline in rats. Monocrotaline, administered with a single intraperitoneal injection (50 mg/Kg), causes pulmonary hypertension and right ventricular hypertrophy, associated with congestive heart failure. beta 1 and beta 2-receptors were characterized in the right ventricle by direct radioligand binding utilizing [125I] Iodocyanopindolol and selective beta 1-(CGP 20712A) and beta 2-(ICI 118551) antagonists. Adenylate cyclase was measured in basal condition and in the presence of different stimulators as isoproterenol with ICI 118551 (beta 1-receptor-stimulated activity), isoproterenol with CGP 20712A (beta 2-receptor-stimulated activity), Gpp(NH)p, NaF and forskolin. In the right ventricle of the failing hearts the beta 1-receptor density decreased selectively (-55.8%) while the beta 2-receptor density was unchanged. Modifications in the adenylate cyclase system were demonstrated: a reduction in the basal and beta 1- and beta 2-stimulated adenylate cyclase activity; a decrease in adenylate cyclase activation elicited by Gpp(NH)p, but not by forskolin and NaF. In conclusion, these data suggest that in monocrotaline-induced heart failure in the rat there is a selective beta 1-receptor down-regulation and an impaired coupling efficiency of G proteins. These results are in line with biochemical changes found in patients with heart failure.
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PMID:[The adrenergic beta system in an experimental model of heart failure]. 196 56

Ventricular hypertrophy should be divided into at least physiologic and patholgic states in order to clarify structural and functional clinical alterations. The elucidation of the structural, functional, and biochemical mechanisms of ventricular hypertrophy is vital to designing effective preventive and therapeutic measures for the hypertensive patient. Tissue markers may help differentiate pathologic from physiologic hypertrophy. Studies have established the concept that norepinephrine may be a myocardial cellular hypertrophying hormone. The studies ranged from the direct application of norepinephrine to isolated myocardial cells to the chronic subhypertensive infusion of norepinephrine into the conscious, free-roaming dog. Norepinephrine infusion can produce physiologic ventricular hypertrophy or a pathologic state of hypertrophic cardiomyopathy, the former by a three- to four-month infusion and the latter by an infusion of more than six months. The biochemical effect of subhypertensive infusion of norepinephrine was studied prior to the production of ventricular hypertrophy, thereby permitting the elucidation of the mechanism of the hypertrophic process. The biochemical stimulus for the production of myocardial cellular hypertrophy is postulated to be a diminution of cyclic AMP and a stimulation of alpha-1 receptors. Because the ventricular septum has the highest content of adenylate cyclase, which does not increase with cyclic AMP, these changes are postulated to be the biochemical basis for septal hypertrophy in the disease entity hypertrophic cardiomyopathy. A unique conscious-canine model for the production of a myocardial infarction capable of creating a controlled localized occlusion of the coronary artery is presented.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of chronic infusion of norepinephrine on cardiac structure, function, and biochemistry: physiologic versus pathologic hypertrophy. 253 29

High-altitude pulmonary arterial hypertension affects people with a long-term residence at altitudes over 2500 m above the sea level and is characterized by elevated pulmonary artery pressure (over 35/15 mmHg). In order to assess the role of beta-adrenoreceptors in the development of high-altitude pulmonary arterial hypertension, we studied the beta-adrenoreceptor density on mononuclear leukocytes in Kirghiz male natives of Eastern Pamir (3600-4200 m above sea level) with the diagnosis of high-altitude pulmonary arterial hypertension, and in healthy men. It was shown that patients with signs of right ventricular hypertrophy (RVH) of the second and third grade have beta-adrenoreceptor density 4.5 times lower than control (2.27 +/- 0.22 vs. 9.85 +/- 1.28 fmol/10(6) cells). Values of Kd also proved to be lower, by 2.5 times (0.57 +/- 0.14 vs. 1.44 +/- 0.18 nM). Stimulation of adenylate cyclase by isoproterenol and other beta-agonists was lower in patients than in controls (+33% and +120%, respectively). These results demonstrate that the desensitization of beta-adrenoreceptors is present in patients with high-altitude pulmonary arterial hypertension associated with severe right ventricular hypertrophy. Patients with pulmonary arterial hypertension due to mitral stenosis do not have any signs of beta-adrenoreceptor desensitization associated with high plasma levels of catecholamines.
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PMID:Human adrenoceptor system response to the development of high altitude pulmonary arterial hypertension. 254 27

We have previously reported that left ventricular hypertrophy in two-kidney, one-clip renal hypertensive rats (2K-1C RHRs) was associated with diminished inotropic responsiveness to isoproterenol and glucagon, suggesting an alteration in the receptor-adenylate cyclase cascade. The present study was performed to investigate the hypothesis that in these same hearts, inotropic responses to alpha-adrenergic stimuli could be enhanced as a compensatory mechanism. alpha-Adrenergic stimulation was achieved by graded phenylephrine infusion (1.02 to 41.2 microM/min) in the presence of propranolol (10(-7) M). The inotropic response was evaluated in the isovolumetric isolated rat heart (Langendorff preparation) paced at 260 beats/min. Results showed a significantly reduced inotropic response to alpha 1-adrenergic stimulation in 2K-1C RHR hearts irrespective of perfusion pressure (50 or 80 mm Hg [PP50 or PP80]) (+427.5 +/- 62.1 vs +1236 +/- 216.4 mm Hg X sec-1 at PP50, p less than .01 and +339 +/- 98.3 vs +1440 +/- 254 mg Hg X sec-1 at PP80, p less than .001) even when comparison was made at equivalent myocardial flow rates (RHR hearts perfused at 80 mm Hg vs control hearts perfused at 50 mm Hg). Quantitative assessment of number of alpha 1-adrenergic receptors (3H-prazosin binding) showed a significant decrease compared with that in age-matched sham-operated normotensive control rats (45 +/- 2.5 vs 64 +/- 1.7 fmol/mg protein, p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired inotropic responses to alpha-adrenergic stimulation in experimental left ventricular hypertrophy. 298 93

We investigated the changes in the membranous beta-adrenoceptor-adenylate cyclase system in the right ventricle, left ventricle and interventricular septum during the progress of monocrotaline-induced right ventricular hypertrophy and failure. The beta-adrenoceptor density was decreased in hypertrophied right ventricle 2 to 4 weeks after treatment. When the rats showed symptoms of right ventricular failure 4 weeks after treatment, the beta-adrenoceptor density was decreased in the interventricular septum. Both basal and forskolin-stimulated adenylate cyclase activities were decreased in the right ventricle at 3 and 4 weeks, and in the interventricular septum at 4 weeks, after treatment, which indicates that the catalytic activity of adenylate cyclase is reduced. Changes in isoproterenol plus Gpp (NH) p- or sodium fluoride-stimulated adenylate cyclase activity were generally similar to those in basal activity. These data indicate that a chamber-specific decrease in beta-adrenoceptor density begins in the early stages of right ventricular hypertrophy, and that beta-adrenoceptor density and adenylate cyclase activity in the interventricular septum are decreased in the advanced stages of heart failure in monocrotaline-treated rats.
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PMID:Intraventricular changes in the beta-adrenoceptor-adenylate cyclase system of the rat heart with the progress of monocrotaline-induced right ventricular hypertrophy. 780 85


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