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)

It was found that repeated transplantation of ACATOL strain cells resulted in a loss of their sensitivity to growth-stimulating effect of pentagastrin. The effect of gastrin receptor antagonist proglumide, on ACATOL cells growth was inconstant. ACATOL tumor was sensitive to VIP and glucagon in vitro (as shown by adenylate cyclase activity assay), that makes the model promising for selecting potent hormone drugs against colorectal cancer.
...
PMID:[The hormonal sensitivity of a transplantable adenocarcinoma of the large intestine]. 222 62

Forskolin stimulated adenylate cyclase activity 55-fold in crude rat pancreatic plasma membranes. Dose-response curves were better fitted by a two-component model with apparent Ka for forskolin of 0.8 microM and 85 microM corresponding, respectively, to 15% and 85% of total activity. Gpp (NH)p alone or the combined presence of GTP plus a hormone (secretin, VIP or CCK-8) potentiated activation through the high affinity forskolin component. These results are in favour of a dual mode of action of forskolin: a high affinity component related to the stimulatory guanine nucleotide-binding regulatory subunit, and a low affinity component more closely related to the catalytic subunit of the enzyme. In dispersed rat pancreatic acini, forskolin increased cyclic AMP levels 26-fold and potentiated the increase induced by secretin, VIP, and CCK-8. It also stimulated the phosphorylation of three particulate proteins (Mr = 21K, 25K and 33K). In terms of secretion, it raised amylase secretion by 60%, a weak effect comparable to that exerted by VIP but much lower than that of secretin or CCK-8. Forskolin did, however, potentiate the secretory effect of CCK-8 (a hormone inducing a redistribution of cellular calcium) while being without influence on the secretory effects of secretin and VIP.
...
PMID:Effects of forskolin on adenylate cyclase activity and amylase secretion in the rat exocrine pancreas. 241 Apr 66

The effect of dopamine D-2 receptor activation on dopamine D-1 stimulated cyclic AMP accumulation was investigated in slices of rat striatum and limbic forebrain (nucleus accumbens and tuberculum olfactorium). In striatal slices the dose-dependent increase in cyclic AMP accumulation due to dopamine (3-100 mumol/l) was enhanced by selective D-2 receptor blockade using (-)-sulpiride (30 mumol/l). In limbic slices the increase in cyclic AMP due to dopamine (3-50 mumol/l) was unaffected by selective D-2 receptor blockade. The enhancement of cyclic AMP accumulation due to the selective D-1 agonist SKF 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; 1 mumol/l) in striatal slices was attenuated in the presence of the selective D-2 receptor agonist LY 171555 (quinpirole hydrochloride; 10 mumol/l). This attenuation was in turn blocked by (-)-sulpiride (10 mumol/l). In limbic slices LY 171555 (10 mumol/l) had no effect on SKF 38393 (1 mumol/l) stimulated cyclic AMP accumulation. Conversely muscarine receptor activation, using carbachol (10 mumol/l), attenuated D-1 stimulated cyclic AMP accumulation in both striatum and limbic forebrain. Dopamine D-2 or muscarine receptor stimulation in either striatal or limbic slices did not attenuate cyclic AMP accumulation due to VIP (vasoactive intestinal polypeptide; 0.5 mumol/l), isoprenaline (10 mumol/l) or 2-chloroadenosine (100 mumol/l). This suggests that in striatal slices, D-2 receptors mediate a selective inhibition of D-1 stimulated cyclic AMP accumulation, but that in the limbic forebrain D-2 receptors are unlikely to be coupled to D-1 receptor-linked adenylate cyclase. These data indicate a fundamental difference in the properties of D-2 receptor-effector coupling in these brain regions.
...
PMID:Dopamine D-2 receptors inhibit D-1 stimulated cyclic AMP accumulation in striatum but not limbic forebrain. 244 Dec 68

Incubation of human SUP T1 lymphoblasts with VIP, helodermin and related peptides induced homologous desensitization within 5 min as indicated by: 1) a secondary decrease in cellular cyclic AMP levels, even in the presence of phosphodiesterase inhibitors, 2) a reduced capacity of cells to bind [125I]helodermin, 3) decreased helodermin stimulation of adenylate cyclase activity in membranes, and 4) unaffected NaF- and Gpp[NH]p-stimulated adenylate cyclase activities. The desensitizing ability of all peptides correlated with their efficacy to occupy cell receptors, except for [D-Phe2]VIP, a partial VIP agonist with low intrinsic activity, that did not desensitize.
...
PMID:VIP and related peptides induce rapid homologous desensitization in the human lymphoma SUP T1 cell line. 247 55

[Acetyl-His1]VIP stimulated adenylate cyclase with higher potency than VIP in membranes from human SUP-T1 lymphoblasts and was used as an efficient radioiodinated ligand with low non-specific binding to evaluate the relationship between receptor occupancy and adenylate cyclase activation and the possible interference of peptide T (an epitope derived from HIV envelope protein gp120). Various peptides inhibited [125I-acetyl-His1]VIP binding and activated the enzyme, their order of potency being: helodermin greater than [acetyl-His1]VIP greater than VIP = PHI = [Phe1]VIP greater than [D-Phe2]VIP = [D-Ala4]VIP = [D-Phe4]PHI greater than or equal to [D-Phe4]VIP greater than [D-His1]VIP giving further support for the existence of a novel subtype of helodermin/VIP receptors. [D-Ala1]peptide T and VIP-(10-28) did not recognize the binding site and did not inhibit, even at high concentration, VIP - or VIP analogue - stimulated adenylate cyclase activities.
...
PMID:Pharmacological characterization of the novel helodermin/VIP receptor present in human SUP-T1 lymphoma cell membranes. 255 9

At the maximally effective concentration of 10 nM, VIP induced a marked (12.5-fold stimulation above basal), and sustained increase in short circuit current in the human intestinal epithelial cell line Cl.19A grown on permeable filters and placed in Ussing chambers. Half-maximal increase of Isc was observed for 0.1 nM VIP. This was well correlated with the VIP-stimulated adenylate cyclase activity (ED50:0.07 nM). Binding studies using 125I-VIP indicated that Cl.19A cells express a peptide-specific VIP receptor with a dissociation constant of 0.07 nM. Covalent labeling of receptors followed by SDS-PAGE analysis of membrane proteins resulted in the identification of a 63,000 dalton binding protein in Cl.19A cells.
...
PMID:VIP receptors and control of short circuit current in the human intestinal clonal cell line Cl.19A. 255 31

We examined the cultured mouse melanoma cell line B16 (clone F1) and its wheat germ agglutinin-resistant variant Wa4 that suffers from abnormal protein glycosylation (a high fucose:sialic acid ratio in glycoproteins). In both cell lines the adenylate cyclase system was endowed with a functional guanine nucleotide binding protein Gs and was efficiently coupled to alpha-MSH receptors. In the B16 cell line F1 studied we also observed an efficient stimulation of adenylate cyclase activity by helodermin, VIP and the VIP analogue [acetyl-His1]VIP, and also by PGE1. In membranes from the lectin-resistant variant Wa4, the stimulations by VIP-like peptides and by PGE1 were reduced by 60% and 50%, respectively, while the stimulation by alpha-MSH remained normal. As other components of the adenylate cyclase system (Gs site, catalytical unit) appeared unchanged in the Wa4 variant, we conclude that impaired glycosylation essentially affected the number of both VIP-like peptide receptors and PGE1 receptors.
...
PMID:Decreased adenylate cyclase activation by helodermin and PGE1 in the lectin-resistant variant Wa4 of the mouse melanoma cell line B16. 255 62

VIP/helodermin receptors and PGE1 receptors coupled to adenylate cyclase underwent rapid homologous desensitization and/or down regulation in the human lymphoma SUP-T1 cell line: helodermin- and PGE1-stimulated adenylate cyclase activities in membranes decreased by 75% and 80%, respectively, after a 16-hr incubation of cells with 30 nM VIP or 0.1 microM PGE1. The adenylate cyclase response to helodermin doubled within 120 min of incubation with fresh medium, this part of the resensitization process being not significantly reduced by cycloheximide. The second slower phase of recovery attained 80% of control values after 8 hr and was significantly affected by cycloheximide added at time 0. These data were corroborated by our observations on [125I]helodermin binding to intact cells. In the case of functional PGE1 receptors, sixty percent of the adenylate cyclase response reappeared within 30-60 min, with the second phase of recovery leading, after 2-3 hr to 80-85% of control values of PGE1-stimulated enzyme activity. This resensitization process to PGE1 was, as a whole, cycloheximide sensitive.
...
PMID:Recovery of VIP/helodermin- and prostaglandin E1-stimulated adenylate cyclase activities in desensitized SUP-T1 human lymphoblasts. 255 61

Somatostatin has been demonstrated to negatively regulate pancreatic growth in vivo. In this study we used the AR4-2J rat pancreatic acinar tumor cell line to investigate the effect of a stable somatostatin analog, SMS 201-995 (SMS) on cell proliferation. SMS induced an antiproliferative effect on both serum or epidermal growth factor (EGF)-induced cell proliferation; exposure of the cells for 48 h to SMS caused a slight inhibition of serum-induced proliferation (maximal inhibition, 26%) and abolished the growth-promoting effect of EGF. Maximal effect was observed with 10 nM SMS, and half-maximal (IC50) effect with 0.06-0.1 nM SMS. Binding studies with an iodinated derivative of SMS, [125I-Tyr3]SMS, revealed the presence of a single class of high affinity binding sites on AR4-2J plasma membranes with an equilibrium dissociation constant of 0.2 +/- 0.03 nM and a binding site number of 1.1 +/- 0.07 pmol/mg protein. Addition of the nonhydrolyzable GTP analog, guanosine 5-[gamma-thio] triphosphate (GTP gamma S), increased the rate of dissociation of the specifically bound peptide in agreement with the coupling of somatostatin receptors with a GTP-binding regulatory protein. The good agreement between the IC50 for SMS inhibition of cell proliferation and the apparent Kd for binding indicates that the characterized binding sites are the somatostatin receptors that mediate the antiproliferative effect of SMS. When cells were grown in serum-free medium EGF stimulated AR4-2J cell proliferation with half-maximal (ED50) and maximal effects at 0.6 and 10 nM EGF, respectively. This stimulatory effect of EGF was mediated by specific receptors, since binding studies with [125I]EGF indicated that AR4-2J cells contained a single class of EGF receptors (13,000 sites/cell), with an affinity constant for [125I]EGF (Kd = 0.9 +/- 0.09 nM) close to the ED50 for EGF stimulation of cell growth. To examine if SMS-induced growth inhibition involved a cAMP-dependent mechanism we first studied the effect of SMS on cAMP production. SMS had no effect on basal cAMP, but completely inhibited VIP-stimulated cAMP production with an IC50 of 0.2 nM. Pertussis toxin, which is known to abolish the inhibitory effect of somatostatin on adenylate cyclase activity in AR4-2J cells, did not reverse the ability of SMS to inhibit cell proliferation as well as EGF-induced cell proliferation. These data indicate that the antiproliferative effect of SMS does not involve the GTP-binding protein-mediated negative coupling of somatostatin receptors to adenylate cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Direct inhibitory effects of a somatostatin analog, SMS 201-995, on AR4-2J cell proliferation via pertussis toxin-sensitive guanosine triphosphate-binding protein-independent mechanism. 256 40

Histamine 0.1 microM-0.1 mM increased adenylate cyclase activity five- to ten-fold in human fundic membranes, with a potency Ka = 3 microM. The histamine dose-response curve was mimicked by the H3 receptor agonist (R) alpha-MeHA, but at 100 times lower potency, Ka = 0.3 mM. Histamine-induced adenylate cyclase activation was abolished by H2, H1 and H3 receptor antagonists, according to the following order of potency IC50: famotidine (0.3 microM) greater than triprolidine (0.1 mM) thioperamide (2 mM), respectively. Famotidine has no action on membrane components activating the adenylate cyclase system, including the Gs subunit of the enzyme stimulated by forskolin and cell surface receptors sensitive to isoproterenol (beta 2-type), PGE2 and VIP. The Schild plot was linear for famotidine (P less than 0.01) with a regression coefficient r = 0.678. The slope of the regression line was 0.64 and differs from unity. Accordingly, famotidine showed a slow onset of inhibition and dissociation from the H2 receptor in human cancerous HGT-1 cells. The results demonstrate that famotidine is a potent and selective H2 receptor antagonist with uncompetitive actions in human gastric mucosa. Consequently, famotidine might be a suitable drug with long-lasting actions in the treatment of Zollinger-Ellison syndrome. The results also confirm and extend the previous observations that (R) alpha-MeHA and thioperamide are two selective ligands at histamine H3 receptor sites. In the human gastric mucosa, these drugs are respectively 330 and 6700 times less potent than histamine and famotidine on the adenylate cyclase system. The possible involvement of histamine H3 receptors in the regulation of gastric secretion is proposed.
...
PMID:Pharmacological control of the human gastric histamine H2 receptor by famotidine: comparison with H1, H2 and H3 receptor agonists and antagonists. 256 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---