Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Guanylate cyclase in the guinea pig fundic mucosa occurred in two enzymatic forms: a "soluble" form and a particulate form. The mean basal activity of the soluble fraction measured in the presence of 300 micrometer guanosine-5'-triphosphate and 5 mM MnCl2 was 72.6 +/- 5.3 pmoles of cyclic GMP per mg of protein per min. Guanylate cyclase activity was dependent on Mn2+; it was increased by sodium azide (NaN3), CaCl2, cysteine, secretin, and cholecystokinin, but it was not influenced by gastrin, histamine, cholinergic esters, prostaglandins E1 and A1. NaN3 (1 mM) decreased the apparent Km for MnCl2 and potentiated the effects of MgCl2. The activity of the particulate fraction represented about 14% of that of the supernatant fraction. The guanylate cyclase activity of that fraction was not modified by NaN3, gastrin, cholinergic agents, secretin, or cholecystokinin. Cysteine inhibited its activity. These data do not support the hypothesis that cyclic GMP acts as a second messenger for the action of cholinergic agents and gastrin in the guinea pig gastric mucosa.
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PMID:Effect of Ca2+, Mg2+, NaN3, cholinergic agents, and gastrointestinal hormones on the guanylate cyclase from guinea pig gastric mucosa. 2 35

Somatostatin has been shown to inhibit the release of various polypeptide hormones including insulin, glucagon, gastrin, thyroid stimulating hormone, and growth hormone. The mechanism by which somatostatin inhibits the release of these various polypeptide hormones has not been fully elucidated. It has been reported that somatostatin increases the level of the second messenger cyclic GMP in rat brain and in the anterior pituitary gland. The present investigation was designed to determine if these responses seen in the anterior pituitary gland and brain were due to activation of guanylate cyclase [GTP-pyrophosphate lyase (cyclizing), E.C.4.6.1.2.], the enzyme that catalyzes the formation of cyclic GMP. Somatostatin at a concentration of 2 pM enhanced guanylate cyclase activity two-fold in rat cerebrum and anterior pituitary gland. This enhancement of guanylate cyclase activity was also seen in rat liver, pancreas, stomach, and small intestine at the same concentration of somatostatin. Increasing the concentration of somatostatin to 20 microM, caused a marked inhibition of guanylate cyclase activity in all these tissues. Dose-reponse curves done on gastric guanylate cyclase activity revealed that over a concentration range of 2 pM to 0.2 microM, somatostatin had a stimulatory effect on guanylate cyclase activity while at concentrations above 10 microM somatostatin was inhibitory to guanylate cyclase activity. The biphasic pattern of enhancement of guanylate cyclase activity at lower concentrations of somatostatin and inhibition at higher concentrations may help to explain some of the discrepancies seen with previous investigations with somatostatin, hormone release, and cyclic nucleotide metabolism.
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PMID:The interrelationship of somatostatin and guanylate cyclase activity. 611 Jan 70

The objective of the present investigation was to determine if gastrin at physiological concentrations has part of its mechanism(s) of action through stimulation of guanylate cyclase (EC 4.6.1.2). Human gastrin (I), pentagastrin, tetragastrin, and gastrin-related tetrapeptide all increased cyclic GMP levels and guanylate cyclase activity in rat gastric mucosa, whole stomach, and duodenum. Maximal stimulation was seen at 1 microM with all of the above. There was no further enhancement of guanylate cyclase with increasing the concentration to the millimolar range. The ED50 for human gastrin and pentagastrin was 0.01 microM, whereas the ED50 was 0.1 microM for tetragastrin and the tetrapeptide. No enhancement of guanylate cyclase activity was seen with decreasing the concentration to 1 nM of the respective gastrins. Cimetidine utilized at 1 microM or 1 mM concentrations partially blocked the augmentation by gastrin suggesting that part of this enhancement was through the histamine 2 receptor which has been shown to be important in pentagastrin-stimulated gastric acid release. Since the block was only partial these data would also indicate that some part of gastrin's activation of this enzyme is not mediated through the histamine 2 receptor.
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PMID:Cimetidine partially blocks gastrin's activation of gastric mucosal guanylate cyclase. 613 39

The existence of Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C), the effect of gastrin on phospholipid metabolism and guanylate cyclase activity were investigated to elucidate the cellular mechanism of action of gastrin on the corporal mucosa of the canine stomach. Protein kinase activity was determined by measuring the incorporation of [32P] into calf thymus H1-histone from [32P]-ATP. One unit of protein kinase was defined as the amount of enzyme which incorporated 1 pmol of phosphate from ATP into H1-histone. Protein kinase C was found in 100,000xg supernatant of homogenate fractionated by a DEAE-cellulose column chromatography. Characteristics of further purified protein kinase C, such as dependency on divalent cations and phospholipids, were in agreement with those of previously reported protein kinase C in other tissues. Furthermore, the gastric corporal mucosa was found to contain protein kinase C in large quantities. The specific activity of protein kinase C was 26,000 units/mg protein. The phospholipid metabolism was evaluated by the incorporation of [14C]-glycerol-3-phosphate and the change of the radioactivity of [32P] in individual phospholipids. Each phospholipid was extracted from the gastric corporal mucosa and isolated by thin layer chromatography. Guanylate cyclase activity was determined by measuring the cGMP produced, using radioimmunoassay. Gastrin significantly increased the incorporation of [14C]-glycerol-3-phosphate into phosphatidylethanolamine in the presence of acetylcholine (Ach). Ach increased the uptake of the tracer into phosphatidylinositol significantly, and the increase was enhanced by the simultaneous addition of gastrin. In the experiments with [32P]-labeled phospholipids, gastrin increased the incorporation of [32P] into phosphatidylethanolamine significantly. The significant increase of the radioactivity in phosphatidylinositol by Ach failed to be enhanced by gastrin, but that of phosphatidylethanolamine by Ach was enhanced by gastrin. No stimulation of guanylate cyclase activity by gastrin was detected in the dispersed gastric corporal mucosal cells. These results indicate that gastric corporal mucosa was one of the most abundant tissues in which protein kinase C was contained, when compared with various mammalian tissues previously reported by Minakuchi, Nishizuka, et al. Nishizuka et al, recently proposed the novel hypothesis that phosphatidylinositol turnover activated by cAMP-independent agonists will be essentially required to activate protein kinase C. Our results suggest that gastrin can provoke phospholipids turnover including phosphatidylinositol turnover in gastric corporal mucosa. Therefore, our data indicate the possibility that the protein kinase C system plays an important role in the cellular mechanism of action of gastrin on gastric corporal mucosa.
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PMID:[The cellular mechanism of action of gastrin on the corporal mucosa of the canine stomach. (2) Ca2+-activated, phospholipid-dependent protein kinase and phospholipid turnover--possible mediator of gastrin action]. 613 23

Gastrectomy increased pancreatic growth and this effect was associated with an increase in the number of somatostatin-14 (SS) receptors (146% of control) without altering their affinity. SS increased guanylate cyclase activity twofold in pancreatic acinar membranes from gastrectomized rats. The gastrectomy decreased pancreatic SS-like immunoreactivity (SS-LI) content (55% of control levels) and tyrosine phosphatase activity (74% of control levels). Administration of proglumide (20 mg/kg, IP), a gastrin/cholecystokinin (CCK) receptor antagonist, suppressed the inhibitory effect of gastrectomy on basal tyrosine phosphatase activity and SS-LI content, which returned to control levels. Furthermore, proglumide suppressed the increase of the number of SS receptors and of SS-stimulated guanylate cyclase activity induced by gastrectomy. All this suggests that pancreatic acinar cell growth is associated with upregulation of SS receptors, which could represent a mechanism promoted by the cell to negatively regulate the mitogenic activity of pancreatic growth factors such as CCK. In addition, the results also suggest that the negative regulation of tyrosine phosphatase activity may be important in the events involved in the pancreatic hyperplasia observed after gastrectomy.
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PMID:Somatostatin binding capacity, guanylate cyclase and tyrosine phosphatase activities during pancreatic proliferation in the rat induced by gastrectomy. 874 59

New receptor-avid radiotracers are being developed for site-specific in vivo targeting of a myriad of receptors expressed on cancer cells. This review exemplifies strategies being used to design radiometallated peptide conjugates that maximize uptake in tumors and optimize their in vivo pharmacokinetic properties. Efforts to produce synthetic peptide analogues that target the following three receptor systems are highlighted: Gastrin releasing peptide (GRP), alpha-melanocyte stimulating hormone (alpha-MSH), and guanylate cyclase-C (GC-C) receptors.
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PMID:Radiometallated receptor-avid peptide conjugates for specific in vivo targeting of cancer cells. 1151 98

The direct effects of nitric oxide (NO) on enterochromaffin-like (ECL) cells have not yet been demonstrated. In this study we investigated the direct effects of NO donors on rat ECL cells. The NO donor, NOR3 (10 and 100 microM), decreased gastrin-induced histamine release. 100 microM NOR3 increased cGMP levels and reduced gastrin-induced calcium influx. ODQ, an inhibitor of guanylate cyclase, completely blocked NOR3-induced inhibition of histamine release. These results suggest that NO inhibits gastric acid secretion via suppression of gastrin-induced histamine release through a pathway in which NO activates guanylate cyclase, in addition to increasing cGMP levels and reducing gastrin-induced calcium influx. The use of NO as a new type of gastric acid inhibitor that decreases histamine levels in the stomach would be beneficial as increased histamine levels resulting from use of a histamine H2 receptor antagonist or proton pump inhibitor have various effects on tumors and immunological functions.
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PMID:Direct effects of nitric oxide on histamine release from rat enterochromaffin-like cells. 1652 66