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)

The muscarinic receptor system involved in pepsinogen secretion from isolated guinea pig gastric chief cells was investigated by evaluating the effect of muscarinic receptor antagonists on carbamylcholine (CCh)-stimulated chief cell responses. CCh stimulated the hydrolysis of polyphosphoinositide in chief cells at the same concentrations as it stimulated pepsinogen secretion. Each of five different muscarinic receptor antagonists, atropine, pirenzepine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), AF-DX116 and scopolamine, inhibited both pepsinogen secretion and inositol phosphate accumulation stimulated by graded concentrations of CCh. The pA2 values of the antagonists calculated from data on inositol phosphate accumulation and pepsinogen secretion (atropine = scopolamine = 4-DAMP greater than pirenzepine greater than AF-DX116) suggest that the muscarinic acetylcholine receptor in gastric chief cells is the M3 subtype. On the other hand, CCh did not affect the adenylate cyclase/cAMP signaling pathway in gastric chief cells. All pA2 values of the antagonists were also in agreement with the Ki values determined by [3H]NMS binding to chief cells. Furthermore, GTP gamma S reduced [3H]acetylcholine binding to chief cell membranes in a concentration-dependent manner. The present study, therefore, suggests that muscarinic M3 receptors, which may be coupled to a G protein, mediate pepsinogen secretion, probably by activation of the polyphosphoinositide second messenger system in guinea pig gastric chief cells.
...
PMID:M3 muscarinic receptors mediate pepsinogen secretion via polyphosphoinositide hydrolysis in guinea pig gastric chief cells. 132 64

Peptide YY (PYY), found in intestinal endocrine cells, and neuropeptide Y (NPY), a structural analogue of PYY found in neurons, inhibit gastric, pancreatic, and intestinal fluid and electrolyte secretion. We examined the effects of these peptides on dispersed chief cells from guinea pig stomach. PYY and NPY, but not pancreatic polypeptide, starting at nanomolar concentrations, caused a 40-50% inhibition of secretin-, vasoactive intestinal polypeptide-, prostaglandin E2-, and forskolin-induced increases in chief cell adenosine 3',5'-cyclic monophosphate (cAMP) content and pepsinogen secretion. These inhibitory peptides did not alter pepsinogen secretion caused by cholecystokinin, carbamylcholine, A23187, 8-bromo-cAMP, or a phorbol ester. The inhibitory effects of PYY on chief cell cAMP production occurred within 30 s, were independent of phosphodiesterase activity, and did not affect the actions of cholera toxin. However, the inhibitory effects of PYY were abolished when chief cells were preincubated with pertussis toxin, an agent that uncouples inhibitory guanine nucleotide binding (G) proteins from their receptors. In gastric chief cells, PYY and NPY attenuate the stimulatory effects of secretagogues whose actions are mediated by changes in cellular levels of cAMP. PYY-induced attenuation of chief cell adenylate cyclase activity appears to involve activation of inhibitory G proteins.
...
PMID:Actions of peptide YY and neuropeptide Y on chief cells from guinea pig stomach. 164 73

To evaluate whether pretreatment with prostaglandin E2 (PGE2) could desensitize pepsinogen secretion in chief cells from guinea pig, chief cells were pretreated with 10 microM PGE2 for up to 30 min. Desensitization of subsequent PGE2-stimulated secretion was maximal after 15 min, averaging only 29 +/- 9% (SE) of pepsinogen secretion in control cells stimulated with 10 microM PGE2. Desensitization was half-maximal with 30 nM PGE2. PGE2 pretreatment at 4 degrees C did not cause desensitization. In cells pretreated with 10 microM PGE2 for 15 min and then given 60 min to recover, responsiveness increased to 79 +/- 7% of that for control cells stimulated with PGE2. Thus the desensitization was reversible. Pretreatment with PGD2 and PGF2a did not alter subsequent PGE2-mediated secretion. PGE2-induced desensitization was heterologous but mediator specific because pepsinogen secretion was reduced in response to adenosine 3',5'-cyclic monophosphate (cAMP)-mediated agents (secretin and vasoactive intestinal peptide) but not Ca(2+)-mediated agents (CCK-8, gastrin, or carbachol). Pretreating chief cells with 10 microM PGE2 did not significantly alter cAMP generation in response to PGE2, secretin, or 3-isobutyl-1-methylxanthine, suggesting that desensitization was not mediated by an alteration in the receptor-coupled adenylate cyclase system. Because PGE2 pretreatment also desensitized pepsinogen secretion induced by the synthetic cAMP analogues 8-BrcAMP and 2'-O-monobutyryl-8-BrcAMP, it is likely that the ability of PGE2 to desensitize pepsinogen secretion in chief cells isolated from guinea pig is due to a mechanism distal to generation of cAMP.
...
PMID:Prostaglandin E2 desensitizes cAMP-mediated pepsinogen secretion in chief cells. 165 22

Frog esophageal mucosa contains peptide glands which release pepsinogen in response to a variety of secretagogues and serves as a model to examine the inhibitory action of somatostatin. The pepsinogen secretion in response to bethanechol was inhibited by somatostatin in a noncompetitive fashion. The maximal response induced by bethanechol was reduced and the EC50 for bethanechol was increased in the presence of somatostatin. On the other hand, somatostatin showed essentially no effect on pepsinogen release evoked by ionophore A23187, dibutyryl cAMP or by forskolin in the presence of atropine. Atropine was included in the incubation mixture to eliminate the effect of acetylcholine released by forskolin from the intrinsic cholinergic neurons also present in the mucosa. Somatostatin did not exert any significant effect on the basal or the forskolin-stimulated cAMP accumulation in the mucosa, nor the basal or the forskolin-stimulated adenylate cyclase activity in the membranes of the peptic cells isolated from the mucosa. Thus, these results seem to suggest that somatostatin inhibits pepsinogen secretion from frog esophageal mucosa by a cAMP-independent pathway.
...
PMID:Somatostatin inhibits pepsinogen secretion via a cyclic AMP-independent pathway. 167 98

The messenger role of Ca+2, cyclic nucleotides and inositol triphosphates in the stimulation of pepsinogen and mucous secretion were studied using isolated pig [correction of nug] gastric chief cells and guinea pig mucous cells, resp. Pepsinogen secretion was stimulated by agents either working at the postreceptor adenylate cyclase (AC) level (db-cAMP, forskolin) or after 12-o-tetradecanoyl-phorbol-13-acetate (TPA) stimulation of protein kinase C (PK C). Similar secretory effects were observed with histamine (H), carbachol (C) and cholecystokinin (CCK). [Ca-2] in was elevated by C and by CCK, but not by H in both types of cells. Like TPA, both C and CCK, but not H, stimulated the Ca+2-sensitive particulate PK C. H increased the activity of cAMP-dependent PK A. PGE2, C and CCK were found to increase inositol-1,4,5-triphosphate content in mucous cells. The findings indicate that two pathways of the regulation of pepsinogen and mucous secretion (AC-cAMP-PK C and phosphoinositol breakdown cascade) can act synergistically.
...
PMID:[Secondary messengers in the hormonal regulation of the functional activity of the main and mucoid cells in the stomach]. 198 55

Forskolin was found to stimulate pepsinogen secretion from frog esophageal mucosa. The stimulation was dose-dependent and was accompanied with a great increase in tissue cAMP content. The response to forskolin mimicked the action of bethanechol and was not additive with bethanechol. The stimulatory effect of forskolin was inhibited by 50% in the presence of either atropine or tetrodotoxin. On the other hand, incubation in a calcium-free medium not only reduced the response to forskolin by 45% but also eliminated the influence of atropine and tetrodotoxin. These results indicate that forskolin may stimulate pepsinogen secretion from the frog esophageal mucosa via activating adenylate cyclase, and part of its effect may arise from eliciting acetylcholine release from the intrinsic neurons.
...
PMID:Forskolin stimulation of pepsinogen secretion from frog esophageal mucosa is partly mediated by intrinsic cholinergic neurons. 256 47

Pepsinogen secretion (PS) is modulated at the intracellular level by both cAMP and calcium ion. Cholecystokinin octapeptide (CCK-8), a potent stimulus for PS, is believed to act through calcium. The most extensively studied pathway for calcium-mediated modulation involves the formation of calcium/calmodulin complexes, leading to activation of calmodulin. We have therefore examined the hypothesis that an inhibitor of calmodulin might inhibit PS stimulated by CCK-8. The phenothiazine derivative trifluoperazine (TFP) was chosen as a calmodulin antagonist. We measured in vitro secretion of pepsinogen by isolated gastric glands as a function of TFP concentration 10(-6) M-5 X 10(-4) M), in the presence and absence of a maximal concentration of CCK-8 (10(-7) M). Cellular viability was determined by measurement of release of the enzyme lactate dehydrogenase (LDH) into the medium. TFP did not significantly inhibit PS stimulation by CCK-8 at any concentration (P greater than 0.05). At 10(-4) M, TFP actually augmented PS stimulation by CCK-8 (P less than 0.05). TFP alone significantly stimulated PS (P less than 0.05) at 5 X 10(-5) M and above. TFP did not raise cAMP levels at any concentration tested (P less than 0.05), in contrast to the adenylate cyclase activator forskolin, 10(-5) M, which caused a 6- to 37-fold increase (P less than 0.05). TFP, 2 X 10(-4) did not increase LDH levels significantly (P less than 0.05). Thus a calmodulin inhibitor, TFP, paradoxically stimulates PS. This stimulatory effect of TFP is not cAMP-dependent and is not accompanied by a nonspecific release of LDH into the medium.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Paradoxical effect of trifluoperazine, a calmodulin antagonist, on pepsinogen secretion. 301 66

The cellular mechanisms by which pepsinogen (PNG) secretion is controlled are not understood. The aim of this study was to explore whether modulation of PNG secretion is mediated by cAMP or calcium-calmodulin (C-C). PNG secretion in isolated rabbit gastric fundic glands (IGG) was tested, using agents believed to act via cAMP or C-C. IGG were stimulated for 30 minutes with histamine (H) 10(-5) M, isoproterenol (I) 10(-5) M, carbachol (C) 10(-5) M, cholecystokinin-octapeptide (CCK-8) 10(-7) M, forskolin (F) 10(-5) M, 8 bromo-cAMP (8B) 10(-3) M, and A23187 (A) 10(-6) M. PNG levels were determined by spectrophotometric assay of hemoglobin digestion products. PNG amounts secreted were (mean per cent above basal levels of total IGG PNG units +/- SEM): H, -0.02 +/- 0.30%; I, 3.5 +/- 0.9%; C, 5.1 +/- 2.2%; CCK-8, 5.3 +/- 1.5%; F, 10.6 +/- 3.8%; 8B, 13.8 +/- 4.5%; A, 2.1 +/- 1.1%. All secretagogues except H stimulated PNG release significantly above basal levels (p less than 0.05). A primary histaminergic mechanism for pepsinogen secretion is unlikely. Since two other adenylate cyclase activators, isoproterenol and forskolin and the 3':5'-cyclic adenosine monophosphate analog 8-bromo cAMP stimulated pepsinogen secretion, cAMP-dependence is probable. Since carbachol, CCK-8, and A23187, which are believed to act via calcium-calmodulin, also stimulated pepsinogen secretion, this system, too, presumably plays a substantial role. Thus the data support a dual 3':5'-cyclic adenosine monophosphate/calcium-calmodulin modulation of pepsinogen secretion.
...
PMID:Evidence for dual modulation of pepsinogen secretion using isoproterenol, carbachol, CCK-8, forskolin, 8 bromo-cAMP, and A23187 probes. 309 67

To determine the role of the adenylate cyclase system in potentiation of enzyme secretion, we used cholera toxin to activate adenylate cyclase before examining the effects of agents on chief cell cAMP and pepsinogen secretion. Dispersed chief cells were obtained from guinea pig stomach by fractionation of mucosal cells on a Percoll gradient. Incubation of cells with 100 nM cholera toxin for 90 min and subsequent incubation with carbachol or cholecystokinin resulted in augmentation of cellular cAMP and potentiation of pepsinogen secretion. The rate of increase in cAMP with carbachol or cholecystokinin was similar to that for the potentiated secretory response. To determine the role of changes in cell calcium on these effects, we examined the actions of the ionophore A23187. In cells preincubated with cholera toxin, A23187 augmented cAMP and caused potentiation of pepsinogen secretion. The effects of A23187, carbachol, and cholecystokinin on cells preincubated with cholera toxin were abolished by removing extracellular calcium or by adding the calmodulin inhibitor trifluoperazine. These data indicate that in chief cells preincubated with cholera toxin, secretagogue-induced increases in cell calcium concentration activate calmodulin thereby augmenting levels of cAMP and causing potentiation of pepsinogen secretion. Modulation of adenylate cyclase by changes in chief cell calcium concentration appears to be one mechanism whereby secretagogue interaction can result in potentiation of pepsinogen secretion.
...
PMID:Interaction between the calcium and adenylate cyclase messenger systems in dispersed chief cells from guinea pig stomach. Possible cellular mechanism for potentiation of pepsinogen secretion. 310 47

Gastrotropin (GT), a protein previously isolated from porcine ileal mucosa, with a molecular mass of 14,054 daltons, was extracted from canine ileum and purified to homogeneity. The canine and porcine peptides had similar relative molecular mass, charge, hydrophobicity, and amino acid compositions. Direct Edman degradation yielded no free amino acids, indicating a blocked NH2-terminus, and a partial sequence determination of the CNBr fragments demonstrated a high degree of homology with porcine GT. Previous studies have indicated that GT is a potent enterooxyntin, and to further characterize these observations we have investigated the actions of both porcine and canine GT on isolated enriched preparations of guinea pig and dog parietal and chief cells. The results of these studies demonstrate that GT is present in more than one species and that the cellular response to porcine and canine GT is identical. The efficacies of canine and porcine GT preparations in stimulating pepsinogen secretion and [14C]aminopyrine uptake were identical and equal to those of cholecystokinin octapeptide (CCK8) and pentagastrin. GT was 100-fold more potent than either of these two major secretagogues. Maximal [14C]aminopyrine accumulation was observed with 10(-8) M GT, with an ED50 of 2 x 10(-9) M compared to pentagastrin, which caused maximal accumulation at 10(-6) M and had an ED50 of 5 x 10(-8) M. Maximal pepsinogen secretion was observed with 10(-7) M GT, with an ED50 of 10(-10) M, compared to 10(-6) M for CCK8, with an ED50 of 10(-8) M. The maximal chief cell response to GT was unaffected by the addition of CCK8 or carbachol, but responded additively with forskolin, indicating that GT uses the same transduction mechanism as CCK8 and carbachol and does not involve the activation of adenylate cyclase. The ED50 values observed with both parietal and chief cells in these studies were close to the basal circulating levels of GT (3.5 x 10(-9) M) in adult pigs. These results clearly demonstrate that GT is a potent component of the enterooxyntin factor identified in studies of the role of the small bowel in the regulation of gastric secretion.
...
PMID:Isolation and partial characterization of gastrotropin from canine ileum: further studies of the parietal and chief cell response. 316 34


1 2 Next >>

---