scholarly journals Regulation of adenylate cyclase and cyclic AMP phosphodiesterase by 5-hydroxytryptamine and calcium ions in blowfly salivary-gland homogenates

1982 ◽  
Vol 204 (1) ◽  
pp. 153-159 ◽  
Author(s):  
I Litosch ◽  
M Fradin ◽  
M Kasaian ◽  
H S Lee ◽  
J N Fain
Keyword(s):  
Salivary Gland ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Guanine Nucleotides ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Cyclic Amp Phosphodiesterase ◽  
Maximal Stimulation ◽  
Increased Activity ◽  
Stimulation Of

Salivary-gland homogenates contain 5-hydroxytryptamine-stimulated adenylate cyclase. Half-maximal stimulation was obtained with 0.1 microM-5-hydroxytryptamine in the presence of added guanine nucleotides. Gramine antagonized the stimulation of cyclase caused by 5-hydroxytryptamine. In the presence of hormone, guanosine 5′-[gamma-thio]triphosphate produced a marked activation of adenylate cyclase activity. Stimulation of adenylate cyclase by forskolin or fluoride did not require the addition of guanine nucleotides or hormone. In the presence of EGTA, Ca2+ produced a biphasic activation of cyclase activity. Ca2+ at 1-100 microM increased activity, whereas 2000 microM-Ca2+ inhibited cyclase activity. The neuroleptic drugs trifluoperazine and chlorpromazine non-specifically inhibited adenylate cyclase activity even in the absence of Ca2+. The cyclic AMP phosphodiesterase activity in homogenates was not affected by Ca2+ or exogenous calmodulin. This enzyme was also inhibited by trifluoperazine in the absence of Ca2+. These results indicate that Ca2+ elevates adenylate cyclase activity, but had no effect on cyclic AMP phosphodiesterase of salivary-gland homogenates.

Effect of histamine on canine gastric mucosal adenylate cyclase.

1977 ◽  
Vol 232 (1) ◽  
pp. E35
Author(s):  
R R Dozois ◽  
A Wollin ◽  
R D Rettmann ◽  
T P Dousa
Keyword(s):  
Gastric Mucosa ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Antral Mucosa ◽  
Fundic Mucosa ◽  
H2 Receptors ◽  
Dose Dependent ◽  
Stimulation Of

The effects of histamine, Nalpha-dimethylhistamine, 4,5-methylhistamine, Ntau-methylhistamine, pentagastrin, carbachol, and NaF on the adenylate cyclase activity from canine gastric mucosa were investigated in cell-free preparations. In gastric fundic mucosa, histamine (10(-4) M), Nalpha-dimethylhistamine (10(-4) M), 4,5-methylhistamine (10(-4 M), and NaF (10)-2) M) significantly (P less than 0.001) increased adenylate cyclase activity (means+/-SE) by 44.7+/-6.6, 49.4+/-6.7, 34.0+/-6.4, and 572.0+/-100%, respectively, above basal activity. The effect of histamine and Na-dimethyl histamine was dose-dependent. In contrast, other tested agents failed to stimulate the formation of cyclic AMP in gastric fundic mucosa. Metiamide (10(-4) M) blocked the stimulation of fundic mucosa adenylate cyclase by histamine and Nalpha-dimethylhistamine, without significantly altering basal and NaF-induced adenylate cyclase activity. Histamine, however, did not stimulate the adenylate cyclase activity from the gastric antral mucosa. The findings support the proposal that the canine gastric acid response to histamine may be mediated by cyclic AMP formed in response to stimulation of histamine H2-receptors.

scholarly journals N 6-(Phenylisopropyl)adenosine prevents glucagon both blocking insulin's activation of the plasma-membrane cyclic AMP phosphodiesterase and uncoupling hormonal stimulation of adenylate cyclase activity in hepatocytes

1984 ◽  
Vol 222 (1) ◽  
pp. 177-182 ◽  
Author(s):  
A V Wallace ◽  
C M Heyworth ◽  
M D Houslay
Keyword(s):  
Plasma Membrane ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Phosphodiesterase Inhibitor ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Maximal Effect ◽  
Hormonal Stimulation ◽  
Cyclic Amp Phosphodiesterase ◽  
Phenylisopropyl Adenosine

Glucagon (10nM) prevented insulin (10nM) from activating the plasma-membrane cyclic AMP phosphodiesterase. This effect of glucagon was abolished by either PIA [N6-(phenylisopropyl)adenosine] (100nM) or adenosine (10 microM). Neither PIA nor adenosine exerted any effect on the plasma-membrane cyclic AMP phosphodiesterase activity either alone or in combination with glucagon. Furthermore, PIA and adenosine did not potentiate the action of insulin in activating this enzyme. 2-Deoxy-adenosine (10 microM) was ineffective in mimicking the action of adenosine. The effect of PIA in preventing the blockade by glucagon of insulin's action was inhibited by low concentrations of theophylline. Half-maximal effects of PIA were elicited at around 6nM-PIA. It is suggested that adenosine is exerting its effects on this system through an R-type receptor. This receptor does not appear to be directly coupled to adenylate cyclase, however, as PIA did not affect either the activity of adenylate cyclase or intracellular cyclic AMP concentrations. Insulin's activation of the plasma-membrane cyclic AMP phosphodiesterase, in the presence of both glucagon and PIA, was augmented by increasing intracellular cyclic AMP concentrations with either dibutyryl cyclic AMP or the cyclic AMP phosphodiesterase inhibitor Ro-20-1724. PIA also inhibited the ability of glucagon to uncouple (desensitize) adenylate cyclase activity in intact hepatocytes. This occurred at a half-maximal concentration of around 3 microM-PIA. However, if insulin (10 nM) was also present in the incubation medium, PIA exerted its action at a much lower concentration, with a half-maximal effect occurring at around 4 nM.

Regulation of PTH receptor-adenylate cyclase system of canine kidney: influence of Mn2+ on effects of Ca2+, PTH, and GTP

1982 ◽  
Vol 242 (5) ◽  
pp. F457-F462
Author(s):  
E. Bellorin-Font ◽  
J. Tamayo ◽  
K. J. Martin
Keyword(s):  
Enzyme Activity ◽  
Adenylate Cyclase ◽  
Metal Ions ◽  
Guanine Nucleotides ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Adenylate Cyclase System ◽  
Guanine Nucleotide ◽  
Hormone Binding ◽  
Stimulation Of

Metal ions play important roles in the regulation of the activation of adenylate cyclase. Previous studies have suggested that an important site of action of metal ions is at or closely related to the nucleotide regulatory protein. The present studies examine the nature of the regulation of enzyme activity by divalent cations and the influence of Mn2+ on hormone binding and stimulation of adenylate cyclase. Studies were performed in canine renal cortical membranes. Substitution of Mg2+ by Mn2+ was associated with a progressive decline in the ability of GTP or PTH to stimulate adenylate cyclase activity. Mn2+ did not alter specific binding of an iodinated PTH analogue. However, in spite of the loss of guanine nucleotide stimulation of enzyme activity, the effects of guanine nucleotide on PTH binding were not altered in the presence of Mn2+. Substitution of Mg2+ by Mn2+ abolished the inhibitory effect of Ca2+ on basal adenylate cyclase activity. Similarly, the effects of GTP or PTH to enhance the inhibitory effects of Ca2+ on enzyme activity were abolished in the presence of Mn2+. Since Mg2+ and Ca2+ compete for a common allosteric site and Mn2+ abolished the effects of these cations, it would appear that Mn2+ also competes for the binding site of Mg2+ and Ca2+. The present studies demonstrating that Mn2+ does not affect hormone binding or the actions of guanine nucleotides on hormone binding yet totally eliminates the effect of GTP on enzyme activity indicate that the effect of Mn2+ occurs at the level of the interactions of the nucleotide regulatory component with the catalytic unit. In addition, these data suggest that there are two functionally distinct sites of guanine nucleotides with different ionic requirements.

Positive coupling of beta-like adrenergic receptors with adenylate cyclase in the cnidarian Renilla koellikeri

1993 ◽  
Vol 182 (1) ◽  
pp. 131-146 ◽  
Author(s):  
E. W. Awad ◽  
M. Anctil
Keyword(s):  
Adenylate Cyclase ◽  
G Protein ◽  
Radioligand Binding ◽  
Guanine Nucleotides ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Binding Studies ◽  
Beta Adrenergic ◽  
Renilla Koellikeri ◽  
Stimulation Of

Coupling of the previously characterized beta1- and beta2-like adrenoceptors in the sea pansy Renilla koellikeri with adenylate cyclase was examined in membrane preparations from this cnidarian. Adenylate cyclase activity was stimulated by several guanine nucleotides, such as GTP, Gpp(NH)p and GTPgammaS. Fluoride ions and cholera toxin greatly enhanced the enzyme activity, whereas forskolin had no effect on basal or isoproterenol-induced stimulation of the enzyme. The stimulation of adenylate cyclase activity by several beta-adrenergic agonists in different parts of the animal reflected a positive coupling with the beta2- and beta1-like adrenoceptors in autozooid and peduncle tissues, respectively. In addition, isoproterenol-induced stimulation of adenylate cyclase activity was dependent on guanine nucleotides, suggesting coupling mediated by a G protein. The pharmacological profile of various antagonists on isoproterenol-sensitive adenylate cyclase in autozooid and peduncle tissues matched that of previous radioligand binding studies. Isoproterenol-induced stimulation of adenylate cyclase activity in rachidial tissues was partially inhibited by trifluoperazine of (+/−)CGP12177 and was completely blocked in the presence of both antagonists. This suggests that coupling of the enzyme occurs with beta1- and beta2-like adrenoceptors, both being present in the rachis. Serotonin and dopamine were also found to stimulate adenylate cyclase activity. Their stimulatory effect was additive to isoproterenol-induced activation, suggesting the presence of dopaminergic and serotonergic receptors in the tissues of the sea pansy. Along with the data presented previously on beta-adrenergic binding, this study suggests that elements of receptor-dependent G protein signal transduction originated early in invertebrate evolution.

scholarly journals Epidermal growth factor stimulates rat cardiac adenylate cyclase through a GTP-binding regulatory protein

1989 ◽  
Vol 264 (2) ◽  
pp. 563-571 ◽  
Author(s):  
B G Nair ◽  
H M Rashed ◽  
T B Patel
Keyword(s):  
Adenylate Cyclase ◽  
Regulatory Protein ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Camp Content ◽  
Cardiac Membranes ◽  
Maximal Stimulation ◽  
Epidermal Growth ◽  
Perfused Hearts ◽  
Stimulation Of

In isolated perfused rat hearts, epidermal growth factor (EGF; 15 nM) increased cellular cyclic AMP (cAMP) content by 9.5-fold. In rat cardiac membranes, EGF also stimulated adenylate cyclase activity in a dose-dependent manner, with maximal stimulation (35% above control) being observed at 10 nM-EGF. Half-maximal stimulation of adenylate cyclase was observed at 40 pM-EGF. Although the beta-adrenergic-receptor antagonist propranolol markedly attenuated the isoprenaline-mediated increase in cAMP content of perfused hearts and stimulation of adenylate cyclase activity, it did not alter the ability of EGF to elevate tissue cAMP content and stimulate adenylate cyclase. The involvement of a guanine-nucleotide-binding protein (G-protein) in the activation of adenylate cyclase by EGF was indicated by the following evidence. First, the EGF-mediated stimulation of adenylate cyclase required the presence of the non-hydrolysable GTP analogue, guanyl-5′-yl-imidodiphosphate (p[NH]ppG). Maximal stimulation was observed in the presence of 10 microM-p[NH]ppG. Secondly, in the presence of 10 microM-p[NH]ppG, the stable GDP analogue guanosine 5′-[beta-thio]diphosphate at a concentration of 10 microM blocked the stimulation of the adenylate cyclase by 1 nM- and 10 nM-EGF. Third, NaF + AlCl3-stimulated adenylate cyclase activity was not altered by EGF. The ability of EGF to stimulate adenylate cyclase was not affected by pertussis-toxin treatment of cardiac membranes. However, in cholera-toxin-treated cardiac membranes, when the adenylate cyclase activity was stimulated by 2-fold, EGF was ineffective. Finally, PMA by itself did not alter the activity of cardiac adenylate cyclase, but abolished the EGF-mediated stimulation of this enzyme activity. The experimental evidence in the present paper demonstrates, for the first time, that EGF stimulates adenylate cyclase in rat cardiac membranes through a stimulatory GTP-binding regulatory protein, and this effect is manifested in elevated cellular cAMP levels in perfused hearts exposed to EGF.

Antisecretory effects of berberine in rat ileum

1981 ◽  
Vol 241 (3) ◽  
pp. G253-G258 ◽  
Author(s):  
Y. H. Tai ◽  
J. F. Feser ◽  
W. G. Marnane ◽  
J. F. Desjeux
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Rat Ileum ◽  
Ion Secretion ◽  
Stimulation Of

The in vitro antisecretory effects of the alkaloid berberine (1.0 mM) on intestinal ion secretion and mucosal adenylate cyclase and Na-K-ATPase activities were studied in the rat ileum. Mucosal berberine did not alter the individual basal net ion fluxes and basal adenylate cyclase activity but decreased short-circuit current (Isc) and increased the net absorption of chloride plus bicarbonate. In the cholera toxin-treated tissue, mucosal berberine stimulated absorption of Na and Cl and inhibited the increased adenylate cyclase activity but did not change the specific Na-K-ATPase activity, whereas serosal berberine stimulated Na secretion and decreased Isc. Mucosal berberine also decreased Isc, increased Cl permeability, and reversed the ion secretion induced by dibutyryl cyclic AMP, the heat-stable enterotoxin of Escherichia coli, and methylprednisolone administration. The antisecretory effects of mucosal berberine may be explained by stimulation of a Na-Cl-coupled absorptive transport process. The mechanism of action of serosal berberine remains to be elucidated. However, it is clear that mucosal berberine affects intestinal ion transport by mechanisms different from stimulation of the Na pump and probably at a step distal to the production or degradation of cyclic AMP or cyclic GMP.

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