Effect of histamine on canine gastric mucosal adenylate cyclase.

1977 â—½  
Vol 232 (1) â—½  
pp. E35
Author(s):  
R R Dozois â—½  
A Wollin â—½  
R D Rettmann â—½  
T P Dousa
Keyword(s):  
Gastric Mucosa â—½  
Cyclic Amp â—½  
Adenylate Cyclase â—½  
Cyclase Activity â—½  
Adenylate Cyclase Activity â—½  
Antral Mucosa â—½  
Fundic Mucosa â—½  
H2 Receptors â—½  
Dose Dependent â—½  
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.

Prostaglandin E2-binding sites and cAMP production in porcine fundic mucosa

1981 â—½  
Vol 241 (4) â—½  
pp. G313-G320
Author(s):  
B. L. Tepperman â—½  
B. D. Soper
Keyword(s):  
Adenylate Cyclase â—½  
Prostaglandin E2 â—½  
Binding Site â—½  
Binding Sites â—½  
Biologically Active â—½  
Cyclase Activity â—½  
Adenylate Cyclase Activity â—½  
Scatchard Analysis â—½  
Fundic Mucosa â—½  
Stimulation Of

Biologically active [3H]prostaglandin E2 (PGE2) bound rapidly and specifically to membrane fractions from hog fundic mucosa. Optimal binding occurred in the 30,000-g membrane preparation at 37 degrees C (pH 5.0). Scatchard analysis of specific PgE2 binding revealed the presence of a heterogeneous population of binding sites with Kd values and binding site concentrations of approximately 1 X 10(-9) M and 1 fmol/mg prot and 2 X 10(-8) M and 20 fmol/mg prot, respectively. Specific binding was inhibited by the following agents in descending order of potency: PGE1, PGA2, PGD2, 6-keto-PGF1 alpha, and thromboxane B2. Trypsin treatment or boiling reduced or abolished specific PGE2 binding. PGE2 stimulated cAMP formation in the 2,500-g fraction, with an approximate Km of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not b of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not b of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not be localized in these fractions in vitro.

scholarly journals Detection and analysis of agonist-induced formation of the complex of the stimulatory guanine nucleotide-binding protein with adenylate cyclase in intact wild-type and β2-adrenoceptor-expressing NG108-15 cells

Biochemical Journal â—½  
10.1042/bj3080275 â—½  
1995 â—½  
Vol 308 (1) â—½  
pp. 275-281 â—½  
Author(s):  
G D Kim â—½  
I C Carr â—½  
G Milligan
Keyword(s):  
Adenylate Cyclase â—½  
Nucleotide Binding â—½  
Dose Effect â—½  
Cyclase Activity â—½  
Adenylate Cyclase Activity â—½  
Guanine Nucleotide â—½  
Guanine Nucleotide Binding Protein â—½  
Guanine Nucleotide Binding â—½  
Dose Dependent â—½  
Stimulation Of

Neuroblastoma x glioma hybrid, NG108-15, cells appear to express the alpha-subunit of the guanine nucleotide-binding protein Gs in a substantial molar excess over its effector adenylate cyclase [Kim, Adie and Milligan (1994) Eur. J. Biochem. 219, 135-143]. Addition of the IP prostanoid receptor agonist iloprost to intact NG108-15 cells resulted in a dose-dependent increase in formation of the complex between Gs alpha and adenylate cyclase (GSAC) as measured by specific high-affinity binding of [3H]forskolin. NG108-15 cells transfected to express either relatively high (clone beta N22) or low (clone beta N17) levels of beta 2-adrenoceptor both showed dose-dependent increases in specific [3H]forskolin binding in response to the beta-adrenoceptor agonist isoprenaline, and maximally effective concentrations of isoprenaline resulted in the generation of similar numbers of GSAC complexes in both clones. The dose-effect curve for clone beta N22, however, was some 15-fold to the left of that for clone beta N17, which is similar to that noted for isoprenaline-mediated stimulation of adenylate cyclase activity [Adie and Milligan (1994) Biochem. J. 303, 803-808]. In contrast, dose-effect curves for iloprost stimulation of [3H]forskolin binding were not different in clones beta N22 and beta N17. Basal specific [3H]forskolin binding in the absence of agonist was significantly greater in cells of clone beta N22 than clone beta N17. This was not a reflection of higher immunological levels of adenylate cyclase, indicating that the higher basal formation of GSAC probably reflects empty-receptor activation of Gs. This higher basal specific [3H]forskolin binding was partially reversed by propranolol. The addition of the opioid peptide D-Ala-D-Leu-enkephalin to NG108-15 cells did not reduce iloprost-stimulated [3H]forskolin binding even though this peptide inhibits stimulated adenylate cyclase activity by activation of a delta opioid receptor.

scholarly journals The role of GTP in prostaglandin E1 stimulation of adenylate cyclase in platelet membranes

Biochemical Journal â—½  
10.1042/bj2140231 â—½  
1983 â—½  
Vol 214 (1) â—½  
pp. 231-234 â—½  
Author(s):  
J M Stein â—½  
B R Martin
Keyword(s):  
Adenylate Cyclase â—½  
Prostaglandin E1 â—½  
Platelet Membrane â—½  
Cyclase Activity â—½  
Adenylate Cyclase Activity â—½  
Dependent Inhibition â—½  
Dose Dependent Inhibition â—½  
Dose Dependent â—½  
Stimulation Of

Adenylate cyclase activity in platelet membrane preparations was measured in the presence of prostaglandin E1 (PGE1), GTP and a non-hydrolysable analogue of GDP, guanosine 5′-[beta-thio]diphosphate (GDP[beta S]). A dose-dependent inhibition of adenylate cyclase by GDP[beta S] was observed that could be reversed either by adding increased amounts of GTP or of PGE1.

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

Biochemical Journal â—½  
10.1042/bj2040153 â—½  
1982 â—½  
Vol 204 (1) â—½  
pp. 153-159 â—½  
Author(s):  
I Litosch â—½  
M Fradin â—½  
M Kasaian â—½  
H S Lee â—½  
J N Fain
Keyword(s):  
Salivary Gland â—½  
Cyclic Amp â—½  
Adenylate Cyclase â—½  
Guanine Nucleotides â—½  
Cyclase Activity â—½  
Adenylate Cyclase Activity â—½  
Cyclic Amp Phosphodiesterase â—½  
Maximal Stimulation â—½  
Increased Activity â—½  
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.

Antisecretory effects of berberine in rat ileum

1981 â—½  
Vol 241 (3) â—½  
pp. G253-G258 â—½  
Author(s):  
Y. H. Tai â—½  
J. F. Feser â—½  
W. G. Marnane â—½  
J. F. Desjeux
Keyword(s):  
Cyclic Amp â—½  
Adenylate Cyclase â—½  
Short Circuit â—½  
Short Circuit Current â—½  
Cyclase Activity â—½  
Adenylate Cyclase Activity â—½  
Rat Ileum â—½  
Ion Secretion â—½  
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.

scholarly journals The rapid desensitization of glucagon-stimulated adenylate cyclase is a cyclic AMP-independent process that can be mimicked by hormones which stimulate inositol phospholipid metabolism

Biochemical Journal â—½  
10.1042/bj2430039 â—½  
1987 â—½  
Vol 243 (1) â—½  
pp. 39-46 â—½  
Author(s):  
G J Murphy â—½  
V J Hruby â—½  
D Trivedi â—½  
M J O Wakelam â—½  
M D Houslay
Keyword(s):  
Cyclic Amp â—½  
Adenylate Cyclase â—½  
Membrane Fraction â—½  
Phospholipid Metabolism â—½  
Cyclase Activity â—½  
Adenylate Cyclase Activity â—½  
Kinase C â—½  
Independent Process â—½  
Inositol Phospholipid â—½  
Stimulation Of

Treatment of intact hepatocytes with glucagon, TH-glucagon [(1-N-alpha-trinitrophenylhistidine, 12-homoarginine]glucagon), angiotensin or vasopressin led to a rapid time- and dose-dependent loss of the glucagon-stimulated response of the adenylate cyclase activity seen in membrane fractions isolated from these cells. Intracellular cyclic AMP concentrations were only elevated with glucagon. All ligands were capable of causing both desensitization/loss of glucagon-stimulated adenylate cyclase activity and stimulation of inositol phospholipid metabolism in the intact hepatocytes. Maximally effective doses of angiotensin precluded any further inhibition/desensitizing action when either glucagon or TH-glucagon was subsequently added to these intact cells, as has been shown previously for the phorbol ester TPA (12-O-tetradecanoylphorbol 13-acetate) [Heyworth, Wilson, Gawler & Houslay (1985) FEBS Lett. 187, 196-200]. Treatment of intact hepatocytes with these various ligands caused a selective loss of the glucagon-stimulated adenylate cyclase activity in a washed membrane fraction and did not alter the basal, GTP-, NaF- and forskolin-stimulated responses. Angiotensin failed to inhibit glucagon-stimulated adenylate cyclase activity when added directly to a washed membrane fraction from control cells. Glucagon GR2 receptor-stimulated adenylate cyclase is suggested to undergo desensitization/uncoupling through a cyclic AMP-independent process, which involves the stimulation of inositol phospholipid metabolism by glucagon acting through GR1 receptors. This action can be mimicked by other hormones which act on the liver to stimulate inositol phospholipid metabolism. As the phorbol ester TPA also mimics this process, it is proposed that protein kinase C activation plays a pivotal role in the molecular mechanism of desensitization of glucagon-stimulated adenylate cyclase. The site of the lesion in desensitization is shown to be at the level of coupling between the glucagon receptor and the stimulatory guanine nucleotide regulatory protein Gs, and it is suggested that one or both of these components may provide a target for phosphorylation by protein kinase C.

scholarly journals Challenge of hepatocytes by glucagon triggers a rapid modulation of adenylate cyclase activity in isolated membranes

Biochemical Journal â—½  
10.1042/bj2140093 â—½  
1983 â—½  
Vol 214 (1) â—½  
pp. 93-98 â—½  
Author(s):  
C M Heyworth â—½  
M D Houslay
Keyword(s):  
Cyclic Amp â—½  
Adenylate Cyclase â—½  
Regulatory Protein â—½  
Cyclase Activity â—½  
Adenylate Cyclase Activity â—½  
Maximum Effect â—½  
Guanine Nucleotide â—½  
Rapid Modulation â—½  
Guanine Nucleotide Regulatory Protein â—½  
Dose Dependent

Membrane fractions obtained from hepatocytes treated with glucagon exhibited a decreased glucagon (with or without GTP)-stimulated adenylate cyclase activity. A maximum effect was seen in around 5 min. No change in the rate of cyclic AMP production was observed for the basal, NaF-, p[NH]ppG (guanosine 5′-[beta, gamma-imido]-triphosphate)- and GTP-stimulated states of the enzyme. The lag observed in the p[NH]ppG-stimulated adenylate cyclase activity of native membranes was abolished when membranes from glucagon-pretreated cells were used. When Mn2+ replaced Mg2+ in the assays, the magnitude of the apparent desensitization was decreased. Mn2+ abolished the lag of onset of p[NH]ppG-stimulated activity in native membranes. The desensitization process was dose-dependent on glucagon, which exhibited a Ka of 4 X 10(-10) M. Depletion of intracellular ATP did not affect this process. It is suggested that this desensitization occurs at the level of the guanine nucleotide-regulatory protein.

scholarly journals Regulation of GH3 pituitary tumour-cell adenylate cyclase activity by activators of protein kinase C

Biochemical Journal â—½  
10.1042/bj2620829 â—½  
1989 â—½  
Vol 262 (3) â—½  
pp. 829-834 â—½  
Author(s):  
L A Quilliam â—½  
P R M Dobson â—½  
B L Brown
Keyword(s):  
Protein Kinase C â—½  
Protein Kinase â—½  
Cyclic Amp â—½  
Adenylate Cyclase â—½  
Cyclase Activity â—½  
Adenylate Cyclase Activity â—½  
Maximal Response â—½  
Kinase C â—½  
Cyclic Amp Accumulation â—½  
Stimulation Of

The influence of protein kinase C (PKC) activation on cyclic AMP production in GH3 cells has been studied. The stimulation of cyclic AMP accumulation induced by forskolin and cholera toxin was potentiated by 4 beta-phorbol 12,13-dibutyrate (PDBu). Moreover, PDBu, which causes attenuation of the maximal response to vasoactive intestinal polypeptide (VIP), also induced a small right shift in the dose-response curve for VIP-induced cyclic AMP accumulation. PDBu-stimulated cyclic AMP accumulation was unaffected by pretreatment of cells with pertussis toxin or the inhibitory muscarinic agonist, oxotremorine. PDBu stimulation of adenylate cyclase activity required the presence of a cytosolic factor which appeared to translocate to the plasma membrane in response to the phorbol ester. The diacylglycerol-generating agents thyroliberin, bombesin and bacterial phospholipase C each stimulated cyclic AMP accumulation, but, unlike PDBu, did not attenuate the stimulation induced by VIP. These results suggest that PKC affects at least two components of the adenylate cyclase complex. Stimulation of cyclic AMP accumulation is probably due to modification of the catalytic subunit, whereas attenuation of VIP-stimulated cyclic AMP accumulation appears to be due to the phosphorylation of a different site, which may be the VIP receptor.

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