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

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Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcitonin gene-related peptides I and II (CGRP I and II) were found to stimulate cAMP levels by approximately 4-6 fold in human nonpigmented ciliary epithelial cells with half-maximal effective concentrations of 20 x 10(-10) and 3 x 10(-10) M, respectively. Prior exposure of cells to 6 x 10(-7) M phorbol 12-myristate, 13-acetate for 15 min resulted in a 40-50% inhibition of CGRP II-dependent cAMP stimulation. Phorbol didecanoate and dioctanoylglycerol also effectively inhibited, whereas 4 alpha phorbol didecanoate, an ineffective activator of protein kinase C, had no effect. Staurosporine, a protein kinase C inhibitor, blocked the inhibition of cAMP formation by phorbol esters. cAMP stimulation by forskolin or cholera toxin was not inhibited by phorbol esters, suggesting that neither a Gs protein nor adenylyl cyclase is the site of inhibition by protein kinase C. These data therefore suggest that CGRP receptors are required for inhibition of adenylate cyclase by protein kinase C.
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PMID:Calcitonin gene-related peptide stimulates intracellular cAMP via a protein kinase C-controlled mechanism in human ocular ciliary epithelial cells. 128 Jan 18

1. The signal transduction pathway for vasorelaxation induced by human alpha-calcitonin gene-related peptide (human alpha-CGRP) was studied in rat thoracic aortic rings preconstricted with noradrenaline (10(-7) M). 2. Vasorelaxation by human alpha-CGRP was inhibited by haemoglobin (10(-6) M) and methylene blue (10(-5) M) but was unaffected by ibuprofen (10(-5) M). 3. Acetylcholine caused a 16 fold increase in levels of guanosine 3':5'-cyclic monophosphate (cyclic GMP) with levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) being unaltered. Human alpha-CGRP caused a 12 fold increase in levels of cyclic GMP but, in contrast to acetylcholine, evoked a 2.5 fold rise in levels of cyclic AMP. The rises in cyclic nucleotides evoked by human alpha-CGRP and acetylcholine were dependent on the presence of an intact endothelium. 4. NG-nitro-L-arginine (L-NOARG: 10(-5) M), which inhibits nitric oxide synthetase, inhibited the relaxant response to human alpha-CGRP and cyclic GMP accumulation without affecting the cyclic AMP accumulation. 5. The data presented in this paper suggests that human alpha-CGRP relaxes the rat thoracic aorta by releasing nitric oxide and stimulating guanylate cyclase. The stimulation of adenylate cyclase by human alpha-CGRP probably precedes the activation of nitric oxide synthase but could be unrelated to the relaxant response.
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PMID:Human alpha-calcitonin gene-related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide. 136 70

CCK-secreting WE rat medullary thyroid carcinoma cell line resembles other calcitonin-producing (C-cell) lines in that calcium, cAMP, or agents which raise cAMP, dexamethasone, and beta-adrenergic agents all stimulate peptide secretion. Unlike other C-cell lines, the WE cells respond similarly to IBMX (3-isobutyl-1-methyl-xanthine, a phosphodiesterase inhibitor) in the presence and absence of forskolin, implying that these cells secrete substances that raise cAMP levels, whose effect is accentuated by IBMX. Both CGRP and neurotensin, peptides that may be secreted by these cells, caused a small, but significant, increase in CCK secretion. It is possible that these or other secreted substances that activate adenylate cyclase are responsible for the cell's high rate of CCK secretion. Their high rate of CCK synthesis and their regulated secretion suggest that these cells will be a good model for studies of CCK expression, biosynthesis, and processing.
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PMID:Regulation of cholecystokinin secretion from a rat medullary thyroid carcinoma cell line: role of calcium, cyclic nucleotides, glucocorticoids, neurotensin, and calcitonin gene-related peptide. 152 66

Calcitonin gene-related peptide is a 37-amino acid neuropeptide acting as a transmitter of nonadrenergic, noncholinergic nerves in the heart. Binding sites of high affinity have been reported in coronary arteries, in atria, and, of minor density, in ventricular myocardium. These sites are likely linked to G-proteins mediating modifications of ion channel opening probability and duration and to stimulation of adenylate cyclase activity and cAMP-mediated alterations of ion channel activities. In isolated and perfused guinea pig hearts, low concentrations of CGRP (1-3 nM) exerted no chronotropic effect, but increased coronary flow slightly. Atrioventricular conduction duration and effective refractory period of atrioventricular conduction were prolonged by 3 nM of CGRP. The higher concentration of 10 nM increased the sinus rate, and the effects on the atrioventricular node were counterbalanced. HV and QRS duration of the ECG remained essentially unchanged, but persistent ventricular fibrillation was inducible by burst stimulation in all CGRP-treated hearts. Results in human myometrial myocytes indicate that CGRP exerted direct G protein-mediated activation of potassium channels, leading to hyperpolarization and smooth muscle relaxation. Activation of potassium channels, most prominent in smooth muscle relaxation, is likely an additional factor in the cardiostimulatory profile of CGRP.
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PMID:Membrane actions of calcitonin gene-related peptide in cardiac and smooth muscle myocytes. 163 86

From this study, we predicted that the human calcitonin gene-related peptide (hCGRP) fragment hCGRP-(8-37) would be a selective antagonist for CGRP receptors but an agonist for calcitonin (CT) receptors. In rat liver plasma membrane, where CGRP receptors predominate and CT appears to act through these receptors, hCGRP-(8-37) dose dependently displaced 125I-[Tyr0]rat CGRP binding. However, hCGRP-(8-37) had no effect on adenylate cyclase activity in liver plasma membrane. Furthermore, hCGRP-(8-37) inhibited adenylate cyclase activation induced not only by hCGRP but also by hCT. On the other hand, in LLC-PK1 cells, where calcitonin receptors are abundant and CGRP appears to act via these receptors, the bindings of 125I-[Tyr0]rat CGRP and 125I-hCT were both inhibited by hCGRP-(8-37). In contrast to liver membranes, interaction of hCGRP-(8-37) with these receptors led to stimulation of adenosine 3',5'-cyclic monophosphate (cAMP) production in LLC-PK1 cells, and moreover, this fragment did not inhibit the increased production of cAMP induced not only by hCT but also by hCGRP. Thus hCGRP-(8-37) appears to be a useful tool for determining whether the action of CGRP as well as that of CT is mediated via specific CGRP receptors or CT receptors.
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PMID:Calcitonin gene-related peptide receptor antagonist human CGRP-(8-37). 253 79

Calcitonin (CT) gene-related peptide (CGRP)-like immunoreactivity was detected in both the cortex and medullo-papillary portion of human kidneys. The two forms of human CGRP as well as rat CGRP were capable of stimulating renal cortical adenylate cyclase activity in a concentration-related manner, with a half-maximally effective concentration (EC50) similar to that of human CT and approximately 100-1000 times higher than that of salmon CT. However, in the medullo-papillary portion, in which both salmon CT and human CT were inactive, the two forms of human and rat CGRP increased adenylate cyclase activity by 100%, with EC50 values ranging from 36 nmol/L to 1 mumol/L. In cortical membrane preparations the effect of CGRP was additive to that of salmon CT. We concluded that regional differences exist in the effect of CT and CGRP in human renal tissue and that in the medullo-papillary portion and possibly in the cortex, CGRP stimulates adenylate cyclase activity through a CT-independent mechanism.
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PMID:Regional differences of adenylate cyclase stimulation by calcitonin and calcitonin gene-related peptide in the human kidney. 278 70

Calcitonin and calcitonin gene-related peptide stimulate adenylate cyclase activity and plasminogen activator production in cultured renal tubular LLC-PK1 cells. Salmon [125I]calcitonin and human [125I]calcitonin gene-related peptide bound specifically to the cells. Salmon [125I]calcitonin binding was reduced at lower concentrations of non-radioactive salmon calcitonin than of human calcitonin gene-related peptide. For the stimulation of adenylate cyclase activity and plasminogen activator production, the potency of salmon calcitonin was higher than that of human calcitonin and calcitonin gene-related peptide. In a subclone of LLC-PK cells lacking salmon calcitonin binding sites, no specific binding of [125I]CGRP occurred, and adenylate cyclase activity and plasminogen activator production was not increased by the peptides. Thus, in LLC-PK1 cells the stimulation of adenylate cyclase activity and plasminogen activator production by calcitonin gene-related peptide is probably mediated by the calcitonin receptor.
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PMID:Calcitonin and calcitonin gene-related peptide interact with the same receptor in cultured LLC-PK1 kidney cells. 299 13

1 Endothelial cells of human umbilical vein were isolated and cultured in vitro. 2 In these cells there was a concentration-dependent release of prostacyclin and activation of adenylate cyclase by human calcitonin gene-related peptide (hCGRP). The concentration of hCGRP for half-maximum activation of adenylate cyclase (Kact) by hCGRP was 190 nM. 3 Bradykinin induced a ten fold greater release of prostacyclin than CGRP, but did not activate adenylate cyclase. 4 hCGRP may exert its potent vasodilator properties by stimulating release of vasorelaxant substances, including prostacyclin from endothelial cells.
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PMID:Human calcitonin gene-related peptide activates adenylate cyclase and releases prostacyclin from human umbilical vein endothelial cells. 332 63

Using immunohistochemical methods we show that calcitonin gene-related peptide (CGRP, a peptide encoded by the calcitonin gene) is present in chick spinal cord motoneurons. When added to cultured chicken myotubes, CGRP caused an average 1.5-fold increase in levels of surface acetylcholine receptors. Moreover, the effect of CGRP was independent of the one produced by tetrodotoxin, a blocker of membrane electrical activity but not of that caused by cholera toxin, an activator of adenylate cyclase.
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PMID:Calcitonin gene-related peptide, a peptide present in spinal cord motoneurons, increases the number of acetylcholine receptors in primary cultures of chick embryo myotubes. 349 45

Pituitary adenylate cyclase activating peptide (PACAP) is a vasoactive intestinal peptide-like hypothalamic peptide occurring as two variants, PACAP-27 and the C-terminally extended PACAP-38. Immunoreactive PACAP has also been demonstrated in the enteric nervous system and in the innervation of the respiratory tract. We have examined the possibility that PACAP occurs in the sensory nervous system of the rat. Immunocytochemistry revealed PACAP in numerous nerve fibres in the superficial layer of the dorsal horns of the spinal cord, in nerve cell bodies (most of them of small size) of the spinal ganglia and trigeminal ganglia and in nerve fibres running close to and within the surface epithelium in the skin of the nose, the tongue, the larynx-trachea, and the urinary bladder as well as around the ducts of the submandibular gland. In all locations, PACAP co-existed with calcitonin gene-related peptide and substance P, the PACAP-immunoreactive fibres and cell bodies constituting a subpopulation of those storing substance P and/or calcitonin gene-related peptide. Additional PACAP-immunoreactive fibres not associated with epithelia seemed to lack calcitonin gene-related peptide and substance P. Capsaicin treatment reduced the density of PACAP- and calcitonin gene-related peptide/substance P-immunoreactive fibres in the tissues examined. On the whole, the immunocytochemical results agreed with those obtained by radioimmunoassay for PACAP and CGRP. The data favour a role for PACAP in primary sensory neurons.
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PMID:Pituitary adenylate cyclase activating peptide is a sensory neuropeptide: immunocytochemical and immunochemical evidence. 750 77


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