Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A peptide isolated from porcine gut according to its glucagon-like activity in liver (bioactive enteroglucagon) has been characterized immunologically, biologically and chemically: its potency relative to pancreatic glucagon in interacting with an antiglucagon antibody, hepatic glucagon-binding sites and hepatic adenylate cyclase was approximately 100%, 20% and 10%, respectively. In contrast, it is approximately 20-times more potent than glucagon in oxyntic glands, justifying the term 'oxyntomodulin'. Chemically, it consists in the 29 amino acid-peptide glucagon elongated at its C-terminal end by the octapeptide Lys-Arg-Asn-Lys-Asn-Asn-Ile-Ala; accordingly, it is called 'glucagon-37'.
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PMID:Isolation of glucagon-37 (bioactive enteroglucagon/oxyntomodulin) from porcine jejuno-ileum. Characterization of the peptide. 714 Sep 77

O-alkylated analogues (ethyl, propyl, butyl, tert.-butyl) of lysine vasopressin (LVP) and deamino-LVP are partial agonists to LVP in their effect upon activation of adenylate cyclase in porcine kidney membranes. Emax and pD2 values are linearly dependent and both of them are inversely proportional to the overall hydrophobicity of the peptides, expressed in terms of capacity factors in reversed phase high performance liquid chromatography. It is suggested that the increasing hydrophobicity augments the tendency to either a "wrong way" binding, or to a side-side interaction of several peptide ligands bound to a multi-subsite receptor or both. The data circumstantially indicate that the relation between the peptide-receptor interaction and cyclase activation is not a linear one.
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PMID:Effect of O-alkylated analogues of lysine vasopressin on adenylate cyclase of pig kidney membranes. 729 38

Isolated sheep thyroid follicles release insulin-like growth factors (IGF)-I and -II together with IGF-binding proteins (IGFBPs). We previously showed that TSH suppresses the biosynthesis and release of IGFBPs in vitro which may increase the tissue availability of IGFs, allowing a synergy with TSH which potentiates both thyroid growth and function. Many of the actions of TSH on thyroid cell function are dependent upon activation of adenylate cyclase, although increased synthesis of inositol trisphosphate and activation of protein kinase C (PKC) have also been implicated. We have now examined whether probable changes in intracellular cyclic adenosine monophosphate (cAMP) or PKC are involved in TSH-mediated suppression of IGFBP release. Confluent primary cultures of ovine thyroid cells were maintained in serum-free Ham's modified F-12M medium containing transferrin, somatostatin and glycyl-histidyl-lysine (designated 3H), and further supplemented with sodium iodide (10(-8)-10(-3) mol/l), dibutyryl cAMP (0.25-1 mmol/l), forskolin (5-20 mumol/l) or 12-O-tetradecanoylphorbol-13-acetate (TPA; 10(-11)-10(-6) mol/l), with or without exposure to TSH (200 microU/ml). The uptake and organification of Na [125I] by cells was examined after test incubations of up to 48 h, and IGFBPs in conditioned media were analysed by ligand blot using 125I-labelled IGF-II. The PKC activity in the cytosol and plasma membrane fractions of cells was measured by phosphorylation of histone using [gamma-32P]ATP, and PKC immunoreactivity was visualized by Western immunoblot analysis. While dibutyryl cAMP or forskolin largely reproduced the stimulatory effect of TSH on iodine organification, they did not mimic the inhibitory effect of TSH on the secretion of IGFBPs of 43, 34, 28 and 19 kDa. Incubation with physiological or pharmacological concentrations of iodide (10(-6)-10(-3) mol/l) for up to 48 h significantly decreased TSH action on iodide uptake and organification but did not alter the inhibitory action of TSH on IGFBP release. Incubation of cells with 10(-11)-10(-6) mol TPA/l for 24 h inhibited the subsequent ability of TSH both to potentiate iodine organification and to suppress IGFBP release. In 3H medium, PKC activity was predominantly recovered from the membrane fraction but, following incubation for 48 h with TSH, the enzyme was no longer translocated to the membrane and was recovered predominantly from the cytosol.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of 3', 5' cyclic adenosine monophosphate and protein kinase C in the regulation of insulin-like growth factor-binding protein secretion by thyroid-stimulating hormone in isolated ovine thyroid cells. 751 34

In a search for new alpha-subunits of trimeric GTP-binding proteins in human platelets, we prepared leucocyte-free platelet concentrates and analyzed total RNA for areas homologous to known alpha-subunits. RT-PCR based on two degenerate primers revealed the expected band of 495 base pairs and an additional band of 540 base pairs reflecting the alternative splice product of Gs alpha. Following subcloning in pGEM-T vector and sequencing, we identified the alpha-subunits Gi alpha-2 and Gs alpha-S of the regulating GTP-binding proteins of adenyl cyclase as well as Gz alpha whose function is unknown, confirming earlier immunological identification. In addition, we identified Gs alpha-L (differing from Gs alpha-S by an insertion of 45 base pairs), G16 alpha, (a member of the pertussis toxin insensitive Gq-family), and two new variants of both Gs alpha-S and Gs alpha-L each containing a C-A-G triplet. With G16 we have identified another candidate for pertussis-toxin insensitive signal transduction in platelets. The C-A-G containing sequences of Gs alpha lead to an insertion of a Ser-residue, which results in the consensus sequence of a phosphorylation site for protein kinase C (Ser-X-Lys), making these variants candidates for protein kinase C-sensitive cyclic AMP formation.
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PMID:Identification of alpha-subunits of trimeric GTP-binding proteins in human platelets by RT-PCR. 754 94

The ORL1 receptor, an orphan receptor whose human and murine complementary DNAs have recently been characterized, structurally resembles opioid receptors and is negatively coupled with adenylate cyclase. ORL1 transcripts are particularly abundant in the central nervous system. Here we report the isolation, on the basis of its ability to inhibit the cyclase in a stable recombinant CHO(ORL1+) cell line, of a neuropeptide that resembles dynorphin A9 and whose amino acid sequence is Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln. The rat-brain cDNA encodes the peptide flanked by Lys-Arg proteolytic cleavage motifs. The synthetic heptadecapeptide potently inhibits adenylate cyclase in CHO(ORL1+) cells in culture and induces hyperalgesia when administered intracerebroventricularly to mice. Taken together, these data indicate that the newly discovered heptadecapeptide is an endogenous agonist of the ORL1 receptor and that it may be endowed with pro-nociceptive properties.
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PMID:Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. 756 39

The octapeptide Gly-Lys-Val-Leu-Lys-Lys-Arg-Arg (termed leukocorticotropin, LCT) corresponding to the ACTH-like sequence 81-88 of human pro-interleukin-1 alpha and its derivative Tyr-Gly-Lys-Val-Leu-Lys-Lys-Arg-Arg were synthesized. The 125I-labeled Tyr-LCT specifically interacts with one type of receptor on the surface of murine splenocytes (Kd = (1.45 +/- 0.04) x 10(-8) M, the number of binding sites is equal to 4500) and with two types of receptors on the surface of murine peritoneal macrophages (Kd1 = (5.9 +/- 1.0) x 10(-9) M and Kd2 = (2.6 +/- 2.2) x 10(-7) M). LCT and Tyr-LCT significantly increase the adenylate cyclase activity of murine peritoneal macrophages. The receptor binding and adenylate cyclase stimulation activity of LCT and Tyr-LCT are inhibited by ACTH (13-24).
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PMID:Receptor-binding properties of the peptides corresponding to the ACTH-like sequence of human pro-interleukin-1 alpha. 759 Sep 7

Adenylate cyclase toxin from Bordetella pertussis requires posttranslational acylation of lysine 983 for the ability to deliver its catalytic domain to the target cell interior and produce cyclic adenosine monophosphate (cell-invasive activity) and to form transmembrane channels (hemolytic activity). When the toxin is expressed in Escherichia coli, it has reduced hemolytic activity, but comparable cell-invasive activity to that of adenylate cyclase toxin from B. pertussis. In contrast to the native protein from B. pertussis, which is exclusively palmitoylated, recombinant toxin from E. coli is acylated at lysine 983 with about 87% palmitoylated and the remainder myristoylated. Furthermore, the recombinant toxin contains an additional palmitoylation on approximately two-thirds of the lysines at position 860. These observations suggest that the site and nature of posttranslational fatty-acylation can be dictated by the bacterial host used for expression and can have a significant, but selective, effect on protein function.
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PMID:Hemolytic, but not cell-invasive activity, of adenylate cyclase toxin is selectively affected by differential fatty-acylation in Escherichia coli. 765 93

The action of Gly-Tyr-NH2, (GY-NH2) and Gly-Tyr-LYS(GYK) on 125I-LH binding, cAMP accumulation and progesterone production was investigated. Incubation of rat luteal cells for 2.5 h with GY-NH2 and GYK at dosage of 0.2 mmol/L caused a significant inhibition of basal and gonadotropin-stimulated steroidogenesis. GY-NH2 and GYK were also found to reduce cAMP formation in response to hCG. The activity of adenylate cyclase of luteal cells was inhibited by 0.2 mmol/LGY-NH2 and GYK. GY-NH2 and GYK at a concentration of 0.2 mmol/L were not found to have an inhibitory effect on 8Br-cAMP-stimulated progesterone production. GY-NH2 and GYK did not affect 125I-LH binding to LH receptors on the luteal cell surface. These results suggest that GY-NH2 and GYK inhibit steroidogenesis at the step of gonadotropin-stimulated cAMP formation in luteal cells. Adenylate cyclase in luteal cells was also inhibited.
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PMID:Study on the mechanism and effects of Gly-Tyr-NH2 and Gly-Tyr-Lys on rat luteal cells in vitro. 771 62

Adenylate cyclase toxin (ACT), a virulence factor of Bordetella pertussis, acquires hemolytic and toxic activities after post-translational modification of the cyaA gene product, CyaA. The exact nature of this modification is unknown, but homology to the related repeat toxin alpha-hemolysin of Escherichia coli suggests that fatty acylation of a lysine residue may be involved. In the present study, we used an in vitro chemical approach to acylate unmodified, inactive adenylate cyclase protoxin by using a new water-soluble compound, acylpyrophosphate. We show that undirected transfer of lauric, myristic, or palmitic acid chains to the CyaA protoxin is able to confer both hemolytic and toxic activities to ACT. The chemically modified protoxin shows a specific requirement for Ca2+ ions for toxic activity, as does the wild type toxin. However, the toxic and hemolytic activities of chemically modified ACT are low in comparison to ACT modified in vivo, suggesting that in vitro fatty acylation of the protoxin involves random modification of nucleophilic residues present in the toxin in contrast to the in vivo modification of specific sites.
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PMID:Chemical fatty acylation confers hemolytic and toxic activities to adenylate cyclase protoxin of Bordetella pertussis. 780 9

To elucidate the effect of somatostatin and its mechanism of action on airway beta-adrenergic function, we studied canine bronchial smooth muscle under isometric conditions in vitro. Somatostatin (10(-6) M) inhibited the salbutamol-induced relaxation, so that the salbutamol concentration-response curves were displaced to higher concentrations (P < 0.01). This inhibition was dose dependent, the concentration of somatostatin required to produce a half-maximal effect being 10(-8) M. The relaxant responses to forskolin were likewise inhibited by somatostatin, but those to dibutyryl 3',5'--adenosine cyclic monophosphate (DB-cAMP), verapamil and nitroprusside were not. Somatostatin inhibited the salbutamol-induced accumulation of intracellular cAMP. These effects were abolished by the somatostatin antagonist cyclo [7-aminoheptanoyl-Phe-D-Trp-Lys-Thr (Bz)] or pertussis toxin. These observations suggest that somatostatin down-regulates beta-adrenergic function of airway smooth muscle through activation of an inhibitory guanine nucleotide (GTP)-binding regulatory protein, Gi, coupled to adenylate cyclase.
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PMID:Pertussis toxin-sensitive airway beta-adrenergic dysfunction by somatostatin. 790 48


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