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

---

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

Radioligand binding studies identified two classes of 125I-angiotensin II-binding sites in rat liver membranes. High affinity binding sites (Kd = 0.35 +/- 0.13 nM, N = 372 +/- 69 fmol/mg of protein) were inactivated by dithiothreitol (0.1-10 mM) without any apparent change in low affinity binding sites (Kd = 3.1 +/- 0.8 nM, N = 658 +/- 112 fmol/mg of protein). Dithiothreitol inactivation was readily reversible but could be made permanent by alkylation of membrane proteins with iodoacetamide. Angiotensin II stimulation of glycogen phosphorylase in isolated rat hepatocytes (maximal stimulation 780%, EC50 = 0.4 nM) was completely inhibited by 10 mM dithiothreitol, a concentration which also abolished high affinity site binding; phosphorylase stimulation by glucagon and norepinephrine under these conditions was unaltered. Angiotensin II inhibition of glucagon-stimulated adenylate cyclase activity in hepatocytes required higher angiotensin II concentrations (EC50 = 3 nM) than phosphorylase stimulation and was not affected by dithiothreitol. Fractional occupancy of high affinity binding sites by 125I-angiotensin II correlated closely with angiotensin II-mediated phosphorylase stimulation, whereas occupancy of low affinity sites paralleled inhibition of adenylate cyclase activity. These data indicate that the physiologic effects of angiotensin II in rat liver are mediated by two distinct receptors, apparently not interconvertible, and provide the first evidence for angiotensin II receptor subtypes with differing biochemical features and mechanisms of action.
...
PMID:Characterization of angiotensin II receptor subtypes in rat liver. 633 67

Angiotensin binding and the effects of angiotensin on adenylate cyclase activity were determined on purified membranes from the glomerulosa zone of bovine adrenal cortex. Angiotensin II inhibited adenylate cyclase activity in a dose-dependent manner with an A50-value of 2 nM. The angiotensin effect required the presence of GTP. Angiotensin also inhibited ACTH-stimulated activity. Angiotensin binding was sensitive to the same effectors which influenced angiotensin-induced adenylate cyclase inhibition. In the presence of NaCl 100 mM and magnesium, angiotensin interacted with a single population of binding sites (Kd = 4 nM and maximal binding capacity of 440 fmol/mg protein). These results and published data suggest that the ability to inhibit adenylate cyclase might be a general property of angiotensin receptors.
...
PMID:Angiotensin II inhibits adenylate cyclase from adrenal cortex glomerulosa zone. 687 7

The objective of this study was to examine the effect of indapamide on cAMP generation in cardiomyocytes. Viable ventricular myocytes were isolated from adult rat hearts which included normal hearts from Wistar rats and hypertrophic hearts from Dahl S rats. cAMP content was measured by competitive binding assay. In normal heart, indapamide did not alter cAMP concentration; however, indapamide pretreatment markedly accentuated forskolin-stimulated cAMP production. In contrast to the response with forskolin, indapamide did not alter isoproterenol-stimulated cAMP generation, suggesting an interaction of indapamide with adenyl cyclase rather than through the guanine stimulatory pathway affected by beta-adrenergic stimulation by isoproterenol. Male inbred Dahl SS/Jr fed a diet supplemented with an additional 6% NaCl from the age of 3 weeks were randomly allocated to receive either indapamide 2 mg/kg s.c. per day or the diluent (ethanol/sterile water) in the same volume. Indapamide or diluent injections were begun 1 week after commencing the high-salt diet. Cardiac hypertrophy is known to be associated with reductions in cellular cAMP. Indapamide-treated animals had significantly greater myocardial cAMP concentrations than control animals. Hypertrophic Dahl S myocytes from untreated animals were less responsive to forskolin compared to myocytes from animals that had been treated with indapamide. Angiotensin II (Ang)-receptor stimulation with Ang II and muscarinic-receptor stimulation with carbachol, accentuate cAMP stimulation in cardiac hypertrophy, whereas the reverse or inhibition was noted in normal myocardium. In cardiomyocytes from rats that had been treated with indapamide, the usual inhibitory effects of Ang II and carbachol were noted.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effect of indapamide on cyclic adenosine 3',5'-monophosphate signal transduction system in isolated adult rat cardiomyocytes from normal myocardium and cardiac hypertrophy. 750 59

The present experiments were devoted to analyzing the hypothesis that somatostatin (SS) could modulate glomerular filtration rate by interacting with mesangial cells. Studies were performed in cultured human mesangial cells, passages 3-5. Radioligand experiments demonstrated the presence in the cells of two kinds of receptors, with high (dissociation constant 14 pM. Number of sites: 426 fmol/mg) and low (dissociation constant 56 pM. Number of sites: 20, 111 fmol/mg) affinity. SS prevented in a dose-dependent manner the reduction in planar cell surface area induced by 100 nM Angiotensin II (AII). This effect was not inhibited by the blockade of the vasorelaxing prostaglandins (indomethacin, 10 microM), nitric oxide (L-N-methyl-arginine, 0.2 mM), adenylate cyclase (2,5'-dideoxyadenosine, 0.1 mM), or guanylate cyclase (Methylene blue, 30 microM; LY-83583, 10 microM), but it was potentiated by zaprinast, an inhibitor of the cyclic GMP (cGMP)-specific phosphodiesterase. SS also blocked the increase in myosin light chain phosphorylation induced by AII. SS increased cGMP synthesis by cultured human mesangial cells, an effect that seemed to be dependent on the stimulation of a particulate guanylate cyclase. Preincubation of the cells with pertussis toxin (0.5 microgram/ml) inhibited the effect of SS on the AII-dependent changes in planar cell surface area, as well as the SS-dependent cGMP stimulation. In summary, these results demonstrate the ability of SS to relax cultured human mesangial cells, thus supporting a role for this peptide in the regulation of the glomerular filtration rate. The SS-dependent mesangial cell relaxation may be due to changes in the intracellular concentrations of cGMP, as a consequence of the activation of a particulate guanylate cyclase.
...
PMID:Effects of somatostatin on cultured human mesangial cells. 762 80

The two forms of angiotensin II (Ang II) receptors, AT1 and AT2 subtypes, have been demonstrated in many other cells beside the anterior pituitary cells. Attempting to investigate the subtype(s) of Ang II receptors implicated in the multiple transduction mechanisms involved in Ang II stimulation of prolactin (PRL) release by lactotropes, we studied the effect of selective nonpeptidergic Ang II antagonists on the PRL release, adenylate cyclase (AC), and phospholipase C activities. In intact cells, the AT1 antagonist DuP753 blocked Ang II-induced PRL release, reversed in a dose dependent manner Ang II-evoked inositol phosphates production, and inhibited completely the PLC and protein kinase C (PKC) dependent cAMP accumulation induced by Ang II. In membrane preparations, the Ang II receptors were negatively coupled to AC. The AT1 antagonist blocked in a dose dependent manner the inhibitory effect of Ang II on cAMP production. In intact cells, the negative coupling of Ang II receptor with AC was observed only when PKC was down regulated by long term 12-O-tetradecanolylphorbol-13-acetate pretreatment. Ang II was able to inhibit vasoactive intestinal peptide-induced cAMP accumulation, a response which was also prevented by DuP753. The different coupling of Ang II receptor described above implicated only the AT1 type receptor since the AT2 antagonists (PD123177 and PD123319) were ineffective at any doses tested (10(-8) to 10(-5) M). The obtained results indicate that the regulation of PRL secretion involves the AT1 receptor subtype and that this receptor might be coupled to multiple effectors.
...
PMID:Angiotensin II effects on second messengers involved in prolactin secretion are mediated by AT1 receptor in anterior pituitary cells. 770 34

Renovascular and renal excretory responses to intrarenally infused angiotensin II (Ang II) (1 and 3 ng/min, one dose per rat) were assessed in young (approximately 6 weeks of age) anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats acutely treated with captopril. Urinary excretion of cyclic adenosine monophosphate (cAMP) was also measured in these rats to examine whether Ang II has an enhanced ability to inhibit adenylate cyclase activity in SHR. Ang II (1 ng/min i.r.a.) significantly reduced renal blood flow (RBF) and increased renal vascular resistance (RVR) in SHR but not in WKY rats. At this dose, Ang II produced significant decreases in glomerular filtration rate (GFR), filtration fraction (FF), urine volume (UV) and urinary excretion of sodium (UNaV) and potassium (UkV) in SHR without altering any of these parameters in WKY rats. Ang II at either dose did not cause any increase in systemic blood pressure in either SHR or WKY rats. Ang II (3 ng/min i.r.a.) decreased RBF in both SHR and WKY rats to a similar extent. However, the higher dose of Ang II produced significant decrements in GFR, FF, UV, UNaV and fractional excretion of sodium in SHR but not in WKY rats. Also, Ang II at both the doses significantly decreased urinary cAMP excretion rate in SHR without affecting the same in WKY rats. These data demonstrate that, even during the developmental phase of hypertension, the SHR kidney is more responsive to Ang II as compared with the WKY rat kidney. Also, these results suggest that the ability of Ang II to inhibit renal adenylate cyclase activity in young SHR may be enhanced. The exaggerated renal reactivity to Ang II may be an important determinant of the development of hypertension in SHR.
...
PMID:Angiotensin II: enhanced renal responsiveness in young genetically hypertensive rats. 775 79

Angiotensin II (AII) receptors are known to interact with two distinct guanine nucleotide binding proteins, Gq/11 and Gi, in rat adrenal glomerulosa cells to activate phospholipase C and to inhibit adenylate cyclase, respectively. However, in cultured bovine glomerulosa cells AII potentiates rather than inhibits the stimulatory effect of adrenocorticotropin (ACTH) on cAMP levels. This effect of AII was partially mimicked by phorbol 12-myristate 13-acetate (PMA) and was partially inhibited by staurosporine or depletion of protein kinase C but was unaffected by pertussis toxin treatment. No potentiation was detectable in disrupted cells or in membrane preparations. In intact glomerulosa cells, treatment with cyclosporin A or FK506 completely inhibited AII- or PMA-induced potentiation of cAMP production without affecting the response to ACTH. In COS-7 cells transfected with the rat AT1 receptor, AII caused 2-3-fold enhancement of the ACTH-induced cAMP response, an effect that was partially reproduced by PMA. These potentiating actions of AII and PMA were prevented by preincubation with cyclosporin A or FK506, and the latter effect was abolished by rapamycin. These results implicate the Ca2+- and calmodulin-dependent protein phosphatase, calcineurin, in AII-induced enhancement of adenylate cyclase activity in both adrenal glomerulosa and transfected COS-7 cells. The finding that AII enhances ACTH-stimulated production of cAMP by a second messenger-mediated mechanism that involves the participation of calcineurin reveals an additional mode of cross-talk between pathways activated by Ca(2+)-mobilizing and cAMP-generating receptors.
...
PMID:Evidence for participation of calcineurin in potentiation of agonist-stimulated cyclic AMP formation by the calcium-mobilizing hormone, angiotensin II. 792 24

The effects of somatostatin (ST) on the regulation of the glomerular filtration rate have not been extensively studied. The present experiments were designed to analyze this possible relationship. ST alone did not modify the planar cell surface area (PCSA) of cultured rat mesangial cells (CRMC), but it prevented and reversed the reduction in PCSA induced by 10 nM angiotensin II (Ang II) in a dose- and time-dependent manner. ST (1 microM) completely prevented and reversed the increase in the myosin light chain phosphorylation induced by 10 nM Ang II. Incubation with pertussis toxin (PT, 0.5 micrograms/ml) inhibited the effect of ST on the Ang II-dependent changes in PCSA, but this effect was not inhibited by the blockade of the vasodilatory prostaglandins (indomethacin, 10 microM) or nitric oxide (L-N-methyl-arginine, 0.2 mM) synthesis. 2',5'-dideoxyadenosine (DDA, 0.1 mM), an adenylate cyclase blocker, and methylene blue (MB, 30 microM), a soluble guanylate cyclase blocker, did not interfere with the ST inhibitory effect on the Ang II-dependent reduction in PCSA of rat mesangial cells. ST also blocked the reduction in PCSA induced by phorbol myristate acetate (PMA, 300 nM). ST was also able to prevent and revert the Ang II dependent reduction in glomerular cross-sectional area of isolated rat glomeruli, also in a dose- and time-dependent fashion. Finally, intravenous administration of ST (200 ng/kg body wt as a bolus plus a continuous injection of 25 ng/min/kg body wt) partially blocked the reduction in GFR (measured as CIn) and RPF (measured as CPAH) and the increase in filtration fraction induced by the intravenous administration of Ang II (1.7 micrograms/min/kg body wt) in anesthetized rats. In summary, these results suggest that ST could antagonize the renal actions of Ang II, increasing the GFR and RPF decreased by Ang II, and this effect could be dependent, at least partially, on a direct relaxing effect of ST on mesangial cells.
...
PMID:Somatostatin antagonizes angiotensin II effects on mesangial cell contraction and glomerular filtration. 809 76

Angiotensin II stimulates the hepatic synthesis and secretion of angiotensinogen, the substrate of renin. In the present study performed on freshly isolated rat hepatocytes we demonstrate that this effect of angiotensin II is mainly related to a transient inhibition of adenylylcyclase. Agents known to decrease intracellular cAMP (angiotensin II, vasopressin, guanfacine) or the cAMP-antagonist Rp-adenosine-3',5'-cyclic phosphothioate stimulated, whereas cAMP-stimulating agents (isoproterenol, forskolin, glucagon) or the cAMP-agonist Sp-adenosine-3',5'-cyclic phosphothioate inhibited angiotensinogen synthesis. In contrast, all agents known to affect intracellular concentrations of calcium, as confirmed in Fura-2-loaded hepatocytes (Bay K 8644, calcimycin, calmidazolium, ionomycin, or methoxamine) failed to influence the synthesis of angiotensinogen. The inhibitory effect of angiotensin II as well as the stimulatory effect of glucagon on cAMP were inversely related to angiotensinogen mRNA and angiotensinogen secretion over a wide concentration range of both peptides. Both the angiotensin II-dependent inhibition of cAMP and the angiotensin II-induced increase in angiotensinogen mRNA were abolished by a pertussis toxin pretreatment. In hepatocyte membranes, pertussis toxin ADP-ribosylated a single protein (approximately 41 kDa) probably representing the alpha-subunit of the Gi-protein, coupling inhibitory receptors to adenylylcyclase. We further show that the increase of angiotensinogen mRNA and secretion mainly represents the result of mRNA stabilization, since in a nuclear run-on assay, angiotensin II pretreatment of hepatocytes does not significantly alter the rate of [32P]UTP incorporation into angiotensinogen mRNA, whereas angiotensin II prolonged the half-life of angiotensinogen mRNA in transcription-arrested as well as in [3H]uridine pulse-labeled hepatocytes about 2.5-fold from 80 to 190 min. It is concluded that angiotensin II induces an increase in angiotensinogen synthesis in hepatocytes by stabilizing of angiotensinogen mRNA and that this effect is mediated through inhibition of adenylylcyclase.
...
PMID:Angiotensin II stimulates the synthesis of angiotensinogen in hepatocytes by inhibiting adenylylcyclase activity and stabilizing angiotensinogen mRNA. 822 73

Angiotensin II (Ang II), a potent hypertrophic factor for vascular smooth muscle cells (VSMC), induces activation of the ras proto-oncogene product (Ras) and mitogen-activated protein (MAP) kinases, and tyrosine phosphorylation of a focal adhesion-associated protein, paxillin. Forskolin, a direct activator of adenylate cyclase, and dibutyryl cAMP (Bt2 cAMP), a membrane permeable cAMP analogue, potently inhibited Ang II-stimulated protein synthesis. However, they did not inhibit Ang II-induced activation of Ras and MAP kinases. Although both forskolin and Bt2 cAMP potently reduced background tyrosine phosphorylation of paxillin, they allowed Ang II to induce the same reaction. These results indicate that increasing cAMP antagonizes the hypertrophic response to Ang II without affecting Ras and MAP kinase activation in VSMC and suggest that it does not interrupt signaling from the Ang II receptor to focal adhesions.
...
PMID:Increasing cAMP antagonizes hypertrophic response to angiotensin II without affecting Ras and MAP kinase activation in vascular smooth muscle cells. 894 20


<< Previous 1 2 3 4 5 6 7 Next >>

---