Inositol phosphate accumulation and adenylate cyclase activity were investigated in the cortex of young and aged ethanol-treated rats. Three months of ethanol treatment of young rats decreased maximal stimulation of inositol phosphate accumulation by carbachol by 26%, from 494 ± 76% of basal turnover in control animals to 396 ± 54% in ethanol-treated animals (mean ± SD). In aged rats ethanol-related changes were no longer observed but age-related changes were evident. EC50 was significantly higher than in young animals and maximal stimulation was significantly lower. Basal adenylate cyclase activity in cortical membranes of all groups of animals was not different. Forskolin-stimulated adenylate cyclase activity was not affected by ethanol treatment, but was higher in aged animals. The activity of forskolin-stimulated adenylate cyclase in the presence of carbachol was higher in both young and aged ethanol-treated animals, when compared to young controls. These results suggest that both ethanol ...
The effects of Ca2+-calmodulin on adenylate cyclase activity in EGTA-washed, 27000 g particulate fractions of mouse and rat pancreatic islets were studied. Ca2+ (10 microM)-calmodulin (1 microM) stimulated adenylate cyclase activity 53.1 +/- 5.2 (N = 6)% in the particulate fraction of rat islets. Trifluoperazine (50 microM), a specific inhibitor of calmodulin, inhibited the Ca2+-calmodulin activation of the adenylate cyclase activity of this fraction of rat islets. These results confirm previous reports dealing with Ca2+-Calmodulin and rat islet adenylate cyclase [Valverde, Vandermeers. Anjaneyulu & Malaisse (1979) Science 206, 225-227; Sharp, Wiedenkeller, Kaelin, Siegel & Wollheim (1980) Diabetes 29, 74-77]. In contrast, however, Ca2+ (1-100 microM)-calmodulin (1-10 microM) did not stimulate the adenylate cyclase activity in the EGTA-washed particulate fraction of mouse islets, and trifluoperazine (50 microM) did not inhibit the adenylate cyclase activity of this fraction of mouse islets, ...
1. Sepharose 6B gel-filtration analysis of soluble adenylate cyclase from bovine corpus luteum is described. Both zonal and frontal techniques of analysis were used. 2. Under conditions of zonal analysis recoveries of activity were low. It was concluded that dissociation of two or more components of the adenylate cyclase complex was occurring on the column and that the maintenance of the complex was essential for the high-activity state of the catalytic unit. Two peaks of adenylate cyclase activity, of approximate mol. wts. 45,000 and 160,000 were detected. 3. The theory of frontal analysis (or steady-state gel filtration), applied to the study of the interacting components of the adenylate cyclase complex is discussed, and activity profiles are predicted. Activity profiles obtained experimentally be frontal analysis compared well with the theoretically predicted profile and provide evidence that dissociation of a high-activity complex, with concomitant loss of activity, does occur. Recoveries ...
TY - JOUR. T1 - Hormone-sensitive adenylate cyclase in glomerular cells. Possible role for inflammatory diseases of the glomerulus. AU - Paietta, Elisabeth M.. AU - Schwarzmeier, J. D.. AU - Simbruner, G.. AU - Latzka, U.. AU - Lubec, G.. PY - 1981. Y1 - 1981. N2 - Using the adenylate cyclase assay after Ross the authors examined hormone sensitivity of isolated glomerular cells. cAMP production was increased 1.3-1.6-fold by stimulation with isoproterenol, 1.5-1.8 times by prostaglandin E 1 and 1.4-1.5 times by histamine. The isoproterenol reaction could be completely inhibited by propranolol, the histamine effect was abolished by the H2-blocking agent cimetidine. As a control the authors applied sodium fluoride, which directly activates the catalytic adenylate cyclase unit, increasing the activity 1.8-2.7 times (depending on the method of homogenization). These findings could reflect some physiological or pathophysiological implications, which are discussed.. AB - Using the adenylate cyclase ...
A factor [the feedback regulator (FR)] formed by adipocytes after the stimulation of a cAMP raising hormone has been found to be a potent inhibitor of membrane-bound adenylate cyclase [EC 4.6.1.1.; ATP pyrophosphate-lyase (cyclizing)]. In a standard assay system using rat adipocyte plasma membrane as the source of adenylate cyclase, the FR inhibited adenylate cyclase by lowering the Vmax without affecting the apparent Km for ATP (0.3-0.6 mM). The apparent Ka for epinephrine (5-6 muM) was also not affected by FR. The inhibitory action of FR was partially countered by Mg2+ ions. An increase in phosphorylation of plasma membrane was observed when FR was present in the incubation system. The concentration required for a 50% inhibition was four times higher when adenosine 5-(beta,gamma-imino) triphosphate [AMP-P(NH)P] replaced ATP as the substrate for adenylate cyclase, implying that adenylate cyclase was inactivated by phosphorylation caused by FR. Increase in FR inhibition obtained by adding low ...
TY - JOUR. T1 - Multiple forms of brain adenylate cyclase. T2 - Stimulation by Mn2+. AU - Malamuda, Daniel F.. AU - DiRusso, Concetta C.. AU - Aprille, June R.. PY - 1977/11/23. Y1 - 1977/11/23. N2 - Mn2+-stimulated adenylate cyclase (ATP pyrophosphate-lyase-(cyclizing), EC 4.6.1.1) activity in detergent solubilized preparations from mouse brain. While NaF-stimulated activity was decreased by both solubilization and storage at 0-4°C, the ability of the enzyme to be stimulated by Mn2+ was maintained for up to one week. By including Mn+ in the assay of adenylate cyclase in gel fractions after isoelectric focusing, two distinct peaks of enzyme activity (pI1 = 5.8, pI2 = 6.4) were detected, suggesting the existence of more than one type of catalytic subunit in mouse brain cell membranes.. AB - Mn2+-stimulated adenylate cyclase (ATP pyrophosphate-lyase-(cyclizing), EC 4.6.1.1) activity in detergent solubilized preparations from mouse brain. While NaF-stimulated activity was decreased by both ...
Adenylyl Cyclase Type V Inhibitor, NKY80 - CAS 299442-43-6 - Calbiochem The Adenylyl Cyclase Type V Inhibitor, NKY80, also referenced under CAS 299442-43-6, controls the biological activity of Adenylyl Cyclase Type V. This small molecule/inhibitor is primarily used for Cell Signaling applications. - Find MSDS or SDS, a COA, data sheets and more information.
Aiba H.. The regulatory region of the Escherichia coli cya gene was analyzed by using S1 nuclease mapping and in vitro transcription experiments. The cya gene was transcribed, both in vivo and in vitro, from one major promoter (P2) and two weak promoters (P1 and P1) that are located about 200 base pairs upstream of P2. The transcription from P2 was specifically inhibited by cAMP-CRP (cAMP receptor protein) in vitro. This regulatory mechanism was shown to be physiologically relevant through quantitative analyses of the cya mRNA in intact cells by S1 and dot blot assays. DNase I protection experiments revealed that cAMP-CRP binds to the cya DNA region between +11 and -20, in which a consensus CRP binding sequence is present. Moreover, it was found that cAMP-CRP alters the binding of RNA polymerase to the promoter region, thus inhibiting the transcription of the cya gene.. J. Biol. Chem. 260:3063-3070(1985) [PubMed] [Europe PMC] ...
An important eukaryotic signal transduction pathway involves the regulation of the effector enzyme adenylate cyclase, which produces the second messenger, cAMP. Previous genetic analyses demonstrated that glucose repression of transcription of the Schizosaccharomyces pombe fbp1 gene requires the function of adenylate cyclase, encoded by the git2 gene. As mutations in git2 and in six additional git genes are suppressed by exogenous cAMP, these upstream git genes were proposed to act to produce a glucose-induced cAMP signal. We report here that assays of cAMP levels in wild-type and various mutant S. pombe cells, before and after exposure to glucose, show that this is the case. The data suggest that the cAMP signal results from the activation of adenylate cyclase. Therefore these upstream git genes appear to encode a glucose-induced adenylate cyclase activation pathway. Assays of cAMP on a strain carrying a mutation in the git6 gene, which acts downstream of adenylate cyclase, indicate that ...
We next investigated whether beta gamma subunits play a role in the sensitization of type VI adenylyl cyclase activity; using expression of alpha tau to inhibit beta gamma-mediated effects, we found that the quinpirole-induced sensitization of type VI adenylyl cyclase was abolished ...
Attenuation of inhibitory influence of hormones on adenylyl cyclase systems in the myocardium and brain of obese and type 2 diabetic rats as affected by the intranasal insulin treatment Journal of Evolutionary Biochemistry and Physiology Pleiades Publishing 0022-0930 1608-3202 10.1134/S0022093014050044
H2O2 and oxygen-derived free radicals modulate vasodilator mechanisms.1 2 3 4 5 6 9 The present studies indicate that H2O2 enhances adenylyl cyclase activation and that the effect is dependent (in part) on the presence of iron and is blunted by agents that act to inhibit tyrosine kinase activity.. Our data suggest that the oxygen-derived species mediating the enhancement of adenylyl cyclase activation is either H2O2 itself or the hydroxyl radical. Incubation of cells with xanthine oxidase and purine resulted in a qualitatively similar enhancement of adenylyl cyclase activation. The effect of purine and xanthine oxidase was not blocked by coincubation with superoxide dismutase (which catalyzes the conversion from superoxide anion to H2O2). This suggests that the generation of the superoxide anion is not involved in the mechanism of enhancement of adenylyl cyclase activation. However, pretreatment with either catalase (which catalyzes conversion of H2O2 to water) or with deferoxamine (which ...
TY - JOUR. T1 - Demonstration and Characterization of Opiate Inhibition of the Striatal Adenylate Cyclase. AU - Law, P. Y.. AU - Wu, J.. AU - Koehler, J. E.. AU - Loh, H. H.. PY - 1981/5. Y1 - 1981/5. N2 - Abstract: The conditions in which Leu5‐enkephalin inhibition of striatal adenylate cyclase was observed were defined. It was determined that enkephalin inhibition was dependent on GTP. The apparent Km for GTP in opiate inhibition was determined to be 0.5 and 2 μM when 0.1 mM‐ and 0.5 mM‐ATP were used as substrate. ITP, but not CTP or UTP, could substitute for GTP in the reaction. Though the addition of monovalent cations-Na+,K+, Li+, Cs+, and choline+-stimulated striatal adenylate cyclase activity, enkephalin inhibition of striatal adenylate cyclase did not require Na+ when theophylline was used as the phosphodiesterase inhibitor. Under optimal conditions, i.e., 20 μM‐GTP and 100 mM‐Na+, Leu5‐enkephalin inhibited the striatal adenylate cyclase activity by 23-27%. When the ...
Fingerprint Dive into the research topics of Effect of membrane phospholipid composition changes on adenylate cyclase activity in normal and rous-sarcoma-transformed chicken embryo fibroblasts. Together they form a unique fingerprint. ...
The parasite Trypanosoma brucei possesses a large family of transmembrane receptor-like adenylate cyclases. Activation of these enzymes requires the dimerization of the catalytic domain and typically occurs under stress. Using a dominant-negative strategy, we found that reducing adenylate cyclase activity by about 50% allowed trypanosome growth but reduced the parasites ability to control the early innate immune defense of the host. Specifically, activation of trypanosome adenylate cyclase resulting from parasite phagocytosis by liver myeloid cells inhibited the synthesis of the trypanosome-controlling cytokine tumor necrosis factor-α through activation of protein kinase A in these cells. Thus, adenylate cyclase activity of lyzed trypanosomes favors early host colonization by live parasites. The role of adenylate cyclases at the host-parasite interface could explain the expansion and polymorphism of this gene family.. ...
This study investigates the hypothesis that inflammatory cytokines, interleukin (IL)-1alpha IL-1beta, and tumor necrosis factor (TNF), influence cardiac function by affecting calcium homeostasis and that this effect is mediated by the beta-adrenergic-adenylate cyclase system. After 4 days in culture, neonatal rat ventricular myocytes were treated with cytokines (10 ng/ml) for short (2 h) or longer (18 h) times. Myocyte calcium, contractility, and adenylate cyclase were measured under each condition. Anticipated stepwise increases in adenylate cyclase and intracellular calcium were found in controls (non-cytokine-treated) with 10(-7) M isoproterenol, 10(-7) M isoproterenol + 0.1 mM guanosine triphosphate, and 10(-9) M forskolin. Cells in the presence of cytokine for 2 h show increased basal calcium levels but no changes in adenylate cyclase activities, and isoproterenol fails to elevate adenylate cyclase levels or affect contractile shortening. After long-term treatment with IL-1beta or TNF, but ...
Adenylate cyclase activity of luteinized ovaries from gonadotropin-primed immature rats was stimulated by luteinizing hormone (LH), epinephrine and prostaglandin E1. Treatment of primed rats with human chorionic gonadotropin (hCG) caused a time-dependent loss of the adenylate cyclase response to LH, and the enzyme also became refractory to stimulation by epinephrine. Conversely, treatment of primed rats with epinephrine caused a time-dependent loss of the adenylate cyclase response to epinephrine, but the enzyme remained responsive to LH. The refractoriness of adenylate cyclase to epinephrine after desensitization by hCG or epinephrine was not reversed by Gpp(NH)p. These studies show that "cross-desensitization" of epinephrine-responsive adenylate cyclase activity in the ovary is induced by LH-receptor interaction, whereas β-adrenergic desensitization causes more specific refractoriness to epinephrine with no change in the LH receptor activation mechanism. This suggests the existence of ...
Soluble adenylyl cyclase can function in the nucleus, defining a nuclear microdomain of adenosine 3′,5′-monophosphate (cAMP) signaling. Bundey and Insel discuss the evidence for discrete signaling microdomains of cAMP, including the nucleus and caveolae, and conclude that such microdomains may be defined by the localized, subcellular expression of adenylyl cyclase isoforms.. ...
We have cloned a GC from Paramecium which has an N‐terminal P‐type ATPase‐like domain and a C‐terminal cyclase domain. So far, mammalian GC catalysts are either homodimers fused to an extracellular receptor by a single TM, or soluble heterodimers linked to a nitric oxide‐binding site (Schulz et al., 1991; Yu et al., 1996; Tang and Hurley, 1998; Koesling and Friebe, 1999). The ciliate GC domain differs. It has the unmistakable topology of a mammalian AC complete with catalytic C1a and C2a regions and two prominent membrane anchors, M1 and M2, with six TMs each. Therefore, the ciliate GC is not related to metazoan GCs but is a close relative of metazoan ACs. A striking difference between the ciliate GCs and their mammalian AC congeners was the switch of the C1a and C2a positions. The preference for GTP could be rationalized by looking at three amino acids which determine the nucleotide specifity in the catalytic pocket. In metazoan ACs, glutamine, lysine and aspartate define ATP as a ...
TY - JOUR. T1 - Hormonal stimulation of adenylyl cyclase through Gi-protein βγ subunits. AU - Federman, Alex D.. AU - Conklin, Bruce R.. AU - Schrader, Karen A.. AU - Reed, Randall R. AU - Bourne, Henry R.. PY - 1992/3/12. Y1 - 1992/3/12. N2 - AGONIST-BOUND receptors activate heterotrimeric (αβγ) G proteins by catalysing replacement by GTP of GDP bound to the α subunit, resulting in dissociation of γ-GTP from the βγ subunits. In most cases, α-GTP carries the signal to effectors, as in hormonal stimulation1-4 and inhibition5,6 of adenylyl cyclase by αs and αi respectively. By contrast, genetic evidence in yeast7 and studies in mammalian cells8-10 suggest that βγ subunits of G proteins may also regulate effector pathways. Indeed, of the four recombinant mammalian adenylyl cyclases available for study11-14, two, adenylyl cyclases II and IV, are stimulated by βγ . This effect of βγ requires costimulation by αs-GTP14,15. This conditional pattern of effector responsiveness led to ...
The myocardial potassium uptake during intracoronary isoproterenol stimulation was characterized in 12 anesthetized pigs. The beta-receptor subtype specificity and the effect of adenylate cyclase activation were determined. Potassium concentrations were continuously recorded by PVC-valinomycin minielectrodes in the left atrial cavity and in coronary sinus blood diverted through a shunt to the right atrium. The difference in potassium concentration between the left atrial cavity and coronary sinus, and the accumulated myocardial potassium uptake were calculated after computerized data sampling. By intracoronary drug infusion, changes in heart rate and systemic effects were minimized. Isoproterenol (0.6-0.8 microgram/min), a nonspecific beta-agonist, reduced coronary sinus potassium concentration transiently to a nadir of 0.28 (0.15-0.43) mM (median and 95% confidence interval) below control values (n = 12). The potassium uptake, which amounted to 140 (79-202) mumol/100 g tissue, corresponding to ...
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1CS4: COMPLEX OF GS-ALPHA WITH THE CATALYTIC DOMAINS OF MAMMALIAN ADENYLYL CYCLASE: COMPLEX WITH 2-DEOXY-ADENOSINE 3-MONOPHOSPHATE, PYROPHOSPHATE AND MG
Withdrawal of mice from chronic ethanol treatment results in a decreased responsiveness of striatal (but not mesolimbic) dopamine-sensitive adenylate cyclase activity to stimulation by dopamine. This subsensitivity is not apparent at the time of withdrawal from chronic feeding of ethanol, when animals are still intoxicated, but becomes evident as ethanol is eliminated from the animals. Addition of ethanol in vitro to tissue homogenates from ethanol-withdrawn animals, at concentrations similar to those found in brain at the time of withdrawal, normalizes the response of the adenylate cyclase to dopamine. No difference is evident between control and ethanol-withdrawn animals in stimulation of adenylate cyclase by sodium fluoride. The specificity of the response of striatal adenylate cyclase to stimulation by dopamine, as compared to other transmitters, is unaltered by chronic ethanol feeding. Chronic treatment with ethanol and withdrawal also does not affect the specific binding of spiroperidol in ...
RecName: Full=Adenylate cyclase type 6; EC=4.6.1.1;AltName: Full=Adenylate cyclase type VI;AltName: Full=ATP pyrophosphate-lyase 6;AltName: Full=Adenylyl cyclase 6;AltName: Full=Ca(2+)-inhibitable adenylyl ...
TY - JOUR. T1 - Differential unmasking of adenylate cyclase activity (AC) in cardiac membrane sheets and vesicles. AU - Fleming, J. W.. AU - Besch, H. R.. AU - Jones, L. R.. AU - Watanabe, A. M.. PY - 1978/1/1. Y1 - 1978/1/1. UR - http://www.scopus.com/inward/record.url?scp=0017841068&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0017841068&partnerID=8YFLogxK. M3 - Article. AN - SCOPUS:0017841068. VL - 20. JO - Pharmacologist. JF - Pharmacologist. SN - 0031-7004. IS - 3. ER - ...
In cultured intact LLC-PK1 renal epithelial cells, a nonhydrolyzable ATP analogue, ATP gamma S, inhibits AVP-stimulated cAMP formation. In LLC-PK1 membranes, several ATP analogues inhibit basal, GTP-, forskolin-, and AVP-stimulated adenylate cyclase activity in a dose-dependent manner. The rank order potency of inhibition by ATP analogues suggests that a P2y type of ATP receptor is involved in this inhibition. The compound ATP gamma S inhibits agonist-stimulated adenylate cyclase activity in solubilized and in isobutylmethylxanthine (IBMX) and quinacrine pretreated membranes, suggesting that ATP gamma S inhibition occurs independent of AVP and A1 adenosine receptors and of phospholipase A2 activity. The ATP gamma S inhibition of AVP-stimulated adenylate cyclase activity is not affected by pertussis toxin but is attenuated by GDP beta S, suggesting a possible role for a pertussis toxin insensitive G protein in the inhibition. Exposure of intact LLC-PK cells to ATP gamma S results in a significant ...
Semantic Scholar extracted view of Spermine inhibition of basal and stimulated adenylate cyclase is mediated by the inhibitory GTP-binding protein (Gi). by Carlo Clô et al.
Adenylate cyclase type 5 (EC 4.6.1.1) (ATP pyrophosphate-lyase 5) (Adenylate cyclase type V) (Adenylyl cyclase 5) (Ca(2+)-inhibitable adenylyl cyclase ...
It was assumed through most of the last century that cAMP signaling within mammalian cells proceeded mainly, if not exclusively, through activation of PKA (Kuo and Greengard, 1969). More recently, it has been appreciated that at least three major cAMP-dependent signaling pathways exist in rodent and human cells. A large number of molecular biological and pharmacological investigations have been devoted to parsing the relative contributions of PKA, Epac, and now NCS in cAMP-dependent signaling in mammalian, especially neuroendocrine, cells. These investigations have been fraught with the twin difficulties of establishing both (1) that a particular pathway is, in fact, cAMP-dependent and (2) that the pathway, if cAMP-dependent, relies on either canonical (PKA-dependent) or noncanonical (cAMP sensors other than PKA) signaling. Obviously, reagents for selective stimulation or inhibition of the various isoforms of adenylate cyclase have become increasingly central to these efforts. There is a ...
Because it is the only cell in the human body designed to leave the confines of the body, sperm genes echo those of unicellular life forms. An example is the sperm adenylate cyclase that produces cAMP. The sperm adenylate cyclase gene in homology studies bears the most resemblance to the adenylate cyclase found in cyanobacteria. "One way to think about the human genome is that it contains the memory of unicellular life. When the gametes are made, that genetic memory becomes expressed, and genes that are actually most similar to genes found in other unicellular organisms begin to be expressed in the testes," says John Herr at the University of Virginia. "We call this the ancestral gene program that is activated" during sperm production. (Herr has developed two commercial home tests for male infertility, Sperm Check Fertility and Sperm Check Vasectomy, using biomarkers that are unique to the final stage of sperm development in the testes ...
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Since PAM is a potent inhibitor of AC enzyme activity, it was next investigated if the translocation of PAM from the ER to the plasma membrane results in an inhibition of AC activity. Serum-treatment of HeLa cells reduced the intracellular cAMP accumulation (Fig. 19a). Additionally, serum-treatment decreased Gas- and forskolin-stimulated AC activity to 56.7% and 64.7%, respectively, as compared to untreated cells (Fig. 19b). The observed decrease in AC activity was not due to a change in the AC isoform expression or due to an increased AC expression since no changes in the mRNA expression of AC isoforms was detected (Fig. 19c). To determine if the decrease in stimulated AC activity was mediated by PAM, the amount of endogenous PAM was decreased, employing antisense oligonucleotides against PAM as previously described in Scholich et al., 2001. As shown in Fig. 19d, in HeLa cells treated with antisense ODN the amount of PAM, as determined by Western Blot analysis, was decreased as compared to ...
Nine membrane-bound adenylyl cyclase isoforms catalyze the production of the second messenger cyclic AMPs (cAMP) in response to various stimuli. Reduction of adenylyl cyclase activity has well-documented benefits, including for heart disease and pain. These roles have inspired an attempt to develop isoform selective adenylyl cyclase inhibitors. The lack of true selectivity currently limits exploration of functions and/or treatment of dysfunctions involving adenylyl cyclase/cAMP signaling. The present study demonstrated that a panel of inhibitors described as AC5-selective actually does not discriminate between AC5 and AC6. Likewise, the putative AC1-selective inhibitor, NB001 [5-[[2-(6-amino-9H-purin-9-yl)ethyl]amino]-1-pentanol], does not directly target AC1 to reduce cAMP levels. These results lead to a discussion regarding the need to reinterpret literature using AC5/6-selective molecules.. See article at J Pharmacol Exp Ther 2013, 347:265-275.. ...
Background: The two enzyme families involved in the spatiotemporal control of intracellular cAMP are adenylyl cyclases (AC) which account for its synthesis and phosphodiesterases (PDE) which account for its degradation. In adult cardiomyocytes, AC5 and AC6, and PDE3 and PDE4 are the major isoforms of these two enzyme families, respectively. In addition to their role in modulating cardiac contractile function, AC5 and AC6 are differentially regulated in response to different cardiac stress. However the role of each cyclase in cardioprotection is still controversial. Dynamic inter-regulation between ACs and PDEs has never been investigated yet. In this study, we aimed to determine the effect of AC5 and AC6 overexpression on submembrane PDE3 related cAMP hydrolysis in response to β-adrenergic receptor stimulation.. Methods and Results: Mice with cardiac specific overexperssion of AC5 (AC5Tg) and AC6 (AC6Tg) were produced. The spatiotemporal dynamics of cAMP were determined on both AC5Tg and AC6Tg ...
Gene Information This gene encodes a member of the family of adenylate cyclases which are membrane-associated enzymes that catalyze the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). Mouse studies show that adenylate cyclase 4 along with adenylate cyclases 2 and 3 is expressed in olfactory cilia suggesting that several different adenylate cyclases may couple to olfactory receptors and that there may be multiple receptor-mediated mechanisms for the generation of cAMP signals. Alternative splicing results in transcript variants. [provided by RefSeq Nov 2010]. ...
There are ten isozymes of adenylyl cyclases in mammals, adenylyl cyclase type I-X, (ADCY I-X); In mammals adenylyl cyclase plays an important role in signal transduction pathways in which cAMP is a secondary messenger[13]. ADCY I-IX all share a general structure; They are composed of two trans-membrane regions (M1, M2) which are composed of six membrane-spanning helices and function to keep the enzyme anchored in the membrane, and two cytoplasmic regions (C1, C2) which can be further sub divided (C1a, C1b, C2a, C2b) and are responsible for all catalytic activity, and regulation by G-proteins and forskolin[13]. In solution, the C1a and C2a domains can form heterodimers with each other, either in the same or different enzymes, or they can form homodimers with their identical units on different enzymes[3]. The C1b domain is very large (≈15 kDa) with many regulatory sites, and has a variable structure across isozymes; while the C2b domain is nearly non-existent in many isozymes, and has yet to be ...
There are ten isozymes of adenylyl cyclases in mammals, adenylyl cyclase type I-X, (ADCY I-X); In mammals adenylyl cyclase plays an important role in signal transduction pathways in which cAMP is a secondary messenger[12]. ADCY I-IX all share a general structure; They are composed of two trans-membrane regions (M1, M2) which are composed of six membrane-spanning helices and function to keep the enzyme anchored in the membrane, and two cytoplasmic regions (C1, C2) which can be further sub divided (C1a, C1b, C2a, C2b) and are responsible for all catalytic activity, and regulation by G-proteins and forskolin[12]. In solution, the C1a and C2a domains can form heterodimers with each other, either in the same or different enzymes, or they can form homodimers with their identical units on different enzymes[3]. The C1b domain is very large (≈15 kDa) with many regulatory sites, and has a variable structure across isozymes; while the C2b domain is nearly non-existent in many isozymes, and has yet to be ...
Cyclic AMP is an adenine nucleotide containing one phosphate group which is esterified to both the 3- and 5-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. cAMP is synthesized from ATP by adenylate cyclase. Adenylate cyclase is located at the cell membranes. Adenylate cyclase is activated by the hormones glucagon and adrenaline and by G protein. Liver adenylate cyclase responds more strongly to glucagon, and muscle adenylate cyclase responds more strongly to adrenaline. cAMP decomposition into AMP is catalyzed by the enzyme phosphodiesterase ...
To synchronize a network of pacemakers in the Drosophila brain, a neuropeptide receptor specifically associates with adenylate cyclase 3 to create a
A multitude of signalling cascades are implicated in the homeostasis of articular chondrocytes. However, the identity of these signalling pathways is not fully established. The 3, 5-cyclic AMP-mediated signalling system is considered to be a prototype. Adenylyl cyclase (AC) is an effector enzyme responsible for the synthesis of cAMP. There are 10 mammalian AC isoforms and some of these are differentially regulated by calcium/calmodulin (Ca2+/CaM). Ca2+ is known to play an important role in the development and maintenance of skeletal tissues. Ca2+/CaM-dependent AC isoforms and their temporal expression in articular chondrocytes in rats were identified using RT-PCR and immunohistochemistry techniques. All Ca2+/CaM-dependent AC isoforms were expressed in chondrocytes from all age groups examined. Each isoform was differentially expressed in developing and adult articular chondrocytes. Generally, expression of AC isoforms was observed to increase with age, but the increase was not uniform for all Ca2+/CaM
The exoenzyme S regulon is a set of coordinately regulated virulence genes of Pseudomonas aeruginosa. Proteins encoded by the regulon include a type III secretion and translocation apparatus, regulators of gene expression, and effector proteins. The effector proteins include two enzymes with ADP-ribosyltransferase activity (ExoS and ExoT) and an acute cytotoxin (ExoU). In this study, we identified ExoY as a fourth effector protein of the regulon. ExoY is homologous to the extracellular adenylate cyclases of Bordetella pertussis (CyaA) and Bacillus anthracis (EF). The homology among the three adenylate cyclases is limited to two short regions, one of which possesses an ATP-binding motif. In assays for adenylate cyclase activity, recombinant ExoY (rExoY) catalyzed the formation of cAMP with a specific activity similar to the basal activity of CyaA. In contrast to CyaA and EF, rExoY activity was not stimulated or activated by calmodulin. A 500-fold stimulation of activity was detected following the ...
Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.
The nine membrane-bound isoforms of adenylyl cyclase (AC), via synthesis of the signaling molecule cyclic AMP (cAMP), are involved in many isoform specific physiological functions. All nine isoforms share a similar structural organization; thus, AC isoform differences in physiological function are due to different regulatory profiles. A physiological example is Gβγ, which can conditionally enhance stimulation of ACs 2, 4, 5, 6, and 7, but inhibit ACs 1, 3, and 8. There is also pharmacological control of AC isoforms through small molecule inhibitors. Isoform specific AC functions could be explained by regulatory differences as subtle as single amino acid changes. For both pharmacological targeting and known physiological regulators, differences between isoforms are not well understood. Two approaches were taken to explore AC5/6 isoform selectivity. The first approach was to more completely characterize allegedly AC5 selective small molecule AC inhibitors. The other approach was to examine AC isoform
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
These results suggest that differencial regulation of the AC signaling system in various EC types might also be occuring at the G-protein level. 3. Adenylyl Cyclase Isoforms: Recently, a new aspect in the complexity of the AC signaling system has been introduced at the level of adenylyl cyclase. Over the past 5 years, cDNAs encoding eight AC isoforms have been identitied in mammalian cells 77. Since the physiological actions of agonists that bind to AC-stimulating receptors are quite disparate, it is tempting to speculate that some of these receptors might activate different AC isoform(s). 39. Auerbach, R. 1991. Interactions between cancer cells and the endothelium. In Microcirculation in cancer metastasis. W. Orr, M. Buchanan, and L. Weiss, eds. CRC Press, Boca Raton, FL. pp 169-181. 26 40. , L. W. Morrissey, M. Tu, and J. Joseph. 1985. Expression of organ-specific antigens on capillary endothelial cells. Microvasc. Res. 29:401-411. 41. , R. Hallmann, U. Albrecht, and S. Henke-Fahle. 1986. ...
Stimulation by forskolin of the thyroid adenylate cyclase, cyclic AMP accumulation and iodine metabolism.: Forskolin, a diterpene hypotensive drug, activates ad
Adenylyl cyclases contain two conserved homologous cytoplasmic domains (C1 and C2) that form the catalytic core of the enzyme [21]. Forskolin appears to induce the assembly of these two domains by interacting with the catalytic cleft [21-23]. The affinity between C1 and C2 is also facilitated by Gαs binding. These data have been confirmed by the finding that Forskolin and Gαs stimulate synergistically the cyclase activity [22]. In the presence of Gαs the affinity of Forskolin for the dimer C1/C2 is high (Kd = 0.1 μM), which suggests a stronger affinity for the complete cyclase molecule [23]. The site of interaction of the cyclase (type I or II) for beta/gamma has been located in the C1 b region. This site is independent of the Gαs and Forskolin interaction domains[24]. These findings argue in favor of isolating the cyclase(s) and its associated proteins using Forskolin-agarose affinity chromatography although this procedure enriches indistinctly the different isoforms of the cyclase family. ...
Separation of the catalytic and stimulatory regulatory subunits of rat brain adenylate cyclase.: The catalytic subunit of rat brain adenylate cyclase was separa