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)

Effects of small cardioactive peptide B on the physiology of the isolated heart and gill preparations from the mollusc Aplysia californica were examined. In addition, the effects of small cardioactive peptide B and FMRFamide (Phe-Met-Arg-Phe-NH2) on adenylate cyclase activity were compared in particulate fractions of heart and gill tissues, respectively. Small cardioactive peptide B was found to exert dose-dependent, reversible changes in cardiac activity when perfused through the isolated heart. The EC50 values effecting changes in heart rate and force of contraction were 3 X 10(-11) and 3 X 10(-10) M, respectively; minimum concentrations found to effect changes in heart rate and force of contraction were normally 10(-15) and 10(-12) M, respectively. However, some winter hearts demonstrated threshold sensitivity to small cardioactive peptide B at concentrations as low as 10(-17) M. When perfused through the isolated gill, small cardioactive peptide B was found to suppress the gill withdrawal response amplitude with a threshold concentration of 10(-14) M and an EC50 value of 3 X 10(-11) M. Suppression of the gill withdrawal response amplitude by small cardioactive peptide B was found to be dose dependent and reversible up to a concentration of 10(-9) M. At higher concentrations, the suppression tended to persist irreversibly. Small cardioactive peptide B stimulated adenylate cyclase activity in particulate fractions of both heart and gill tissues with an EC50 of 0.1 and 1.0 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of small cardioactive peptide B on the isolated heart and gill of Aplysia californica. 407 67

Previous work from this laboratory described an association, based on genetic evidence, between a 68 000 dalton protein (p68) and corticotropin (ACTH) sensitive adenylate cyclase activity among variants of the Y1 mouse adrenocortical tumor cell line. To study the nature of this association further, we have purified p68 and raised a polyclonal anti-p68 serum in rabbits. A variant subclone of the Y1 line, in which p68 comprised approximately 10% of total soluble protein, was used as starting material. Purification of p68 was achieved by passage of a 100 000 X g supernatant fraction over DEAE-cellulose, fractionation with ammonium sulfate, and chromatography on hydroxylapatite. The purified protein had an isoelectric point of 7.3, a polarity value of 46%, and a blocked amino terminal end group. A rabbit antiserum raised against the purified p68 had a titer of 1:16 000 and specifically precipitated p68 from extracts of Y1 cells labeled with L-[35S]methionine. Using this antiserum, p68 also was detected in other cell lines including mouse erythroleukemia and Sertoli cells; rat Leydig, ovary, and glioma cells; and Chinese hamster ovary cells. The presence of p68 in a variety of cell types suggests that the function of p68 is not restricted to adrenal cells or to specific actions of ACTH.
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PMID:A 68 000 dalton protein genetically associated with corticotropin-sensitive adenylate cyclase activity. Purification and preliminary characterization using a specific antiserum. 608 78

The present study was undertaken to investigate a possible involvement of phospholipid methyltransferases in the coupling of receptor-mediated stimulation to secretion. Phospholipid methyltransferases were assayed in isolated parotid acini in the presence of carbamoylcholine or isoprenaline. Carbamoylcholine reduced the incorporation of methyl groups into phospholipids, whereas isoprenaline showed no effect. Amylase secretion stimulated either by carbamoylcholine or by isoprenaline could not be affected by inhibitors of methyltransferases (3-deaza-adenosine alone or plus homocysteine thiolactone) under conditions where phospholipid methylation was strongly inhibited. The activity of adenylate cyclase in isolated parotid microsomal membranes was not inhibited or stimulated by S-adenosyl-homocysteine or -methionine respectively. These results indicate that phospholipid methylation does not play an essential role in stimulus-secretion coupling in the parotid gland.
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PMID:Absence of a direct role of phospholipid methylation in stimulus-secretion coupling and control of adenylate cyclase in guinea-pig and rat parotid gland. 618 46

The cycle of protein-carboxyl methylation and demethylation was studied in intact blood platelets. Platelets rapidly incorporated L-[methyl-3H]methionine and after a delay of about 20 min, they evolved [3H]methanol. This evolution, and the amount of [3H] methanol liberated by treatment with base, was inhibited in a dose-dependent fashion by the cyclic nucleotide phosphodiesterase inhibitors 3-isobutyl-1-methylxanthine, papaverine, dipyridamole, and RA233 (2,6-bis(diethanolamino)-4-piperidinopyrimido[5,4-d] pyrimidine). Each of these compounds increased the incorporation of [3H]methionine into platelets. The effects of RA233 were studied in more detail. Inhibition of [3H]methanol production was not potentiated by stimulators of the adenylate cyclase or the guanylate cyclase. The majority of the base-labile radioactivity was trichloroacetic acid precipitable. Thin layer chromatography of extracts of platelets incubated with L-[35S]methionine showed that RA233 did not induce a cellular accumulation of [35S]S-adenosylhomocysteine, and that it actually increased the amount of cellular [35S]S-adenosylmethionine. Discontinuous polyacrylamide gel electrophoresis at acid pH using the cationic detergent benzyldimethyl-n-hexadecylammonium chloride of platelets incubated with [3H]methionine showed incorporation of radioactivity into more than 30 protein bands, including one which co-migrates with calmodulin. The incorporation into the majority of these bands was inhibited by RA233 in a dose-dependent fashion. It is suggested that caution should be used in ascribing the pharmacological effects of known phosphodiesterase inhibitors to increases in cyclic nucleotides, because some of these effects could be due to inhibition of protein carboxyl methylation.
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PMID:Inhibitors of cyclic nucleotide phosphodiesterases inhibit protein carboxyl methylation in intact blood platelets. 619 23

The light chain of type C2 toxin produced by Clostridium botulinum was isolated by high-performance liquid chromatography. The protein eluted as a single peak; as judged by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, it had an apparent molecular weight of 51,000 daltons. The light chain was an enzyme that possessed ADP-ribosylating activity. In experiments with synthetic substrates (homo-poly-L-amino acids; alanine, arginine, asparagine, aspartic acid, histidine, leucine, lysine, methionine, phenylalanine, proline, serine and tryptophan), only poly-L-arginine was ADP-ribosylated by the enzyme. In experiments with endogenous substrates (50,000 X g pellet and 50,000 X g supernatant from homogenates of mouse brain, liver and lung), the enzyme ADP-ribosylated proteins or polypeptides in both the particulate and soluble fractions. ADP-ribosylation of the soluble substrate was antagonized by adenine (K1 approximately 2.1 X 10(-5) M) and by adenosine (K1 approximately 2.7 X 10(-4) M); the reaction was reversed by a large molar excess of nicotinamide (0.1 M). ADP-ribosylation of soluble substrate was diminished when the substrate had been pretreated with 1,2-cyclohexane-dione (0.1 M), a site reactive reagent that modified selectively arginine residues. Neither the light chain nor the heavy chain of the binary toxin possessed adenylate cyclase activity. Tissue fractions did possess endogenous adenylate cyclase activity, but the toxin did not stimulate this activity. The data indicate that the binary toxin produced by Clostridium botulinum resembles other protein toxins.
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PMID:Molecular basis for the pharmacological actions of Clostridium botulinum type C2 toxin. 623 95

In primary cultures of chick 11-day embryonic tissue a number of phosphodiesterase inhibitors were found to elevate acetylcholine receptor levels. Of these agents, Ro20-1724 was the most effective, elevating surface receptor content by 2-fold after 48 h of treatment. 8-Br-cAMP and cholera toxin, a natural activator of adenylate cyclase, mimicked the effect of Ro20-1724, while 8-Br-cGMP and dibutyryl cGMP had no effect. Cholera toxin, 8-Br-cAMP, and Ro20-1724 all increased the insertion rate of new receptor into the surface membrane without altering degradation. The enhanced insertion appears related to an actual increase in synthesis since total acetylcholine receptor was elevated by exposure to cholera toxin. In contrast, no change in creatine phosphokinase activity, myosin heavy chain content, or [35S] methionine incorporation into total cellular protein was observed during cholera toxin treatment. These results suggest that cAMP plays a role in the regulation of acetylcholine receptor.
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PMID:Regulation of acetylcholine receptor by cyclic AMP. 624 32

1. A comparison has been made of the ability of seven calmodulin derivatives to displace 125I-labeled calmodulin and to activate adenylate cyclase in a brain particulate fraction. The activation of brain-soluble cyclic-nucleotide phosphodiesterase by the same calmodulin derivatives was examined in parallel. 2. In general, the dose for half-maximal inhibition of 125I-labeled calmodulin binding and the apparent Km of adenylate cyclase activation were comparable in brain membranes. These concentrations were 20--40-times higher than the corresponding apparent Km values of activation of cyclic-nucleotide phosphodiesterase. 3. Modifying the single histidine residue or both tyrosine residues exerted no influence on the biological properties of calmodulin. The carboxymethylation of two methionine residues or the amidation of several carboxyl groups reduced the activation properties of calmodulin on adenylate cyclase and cyclic-nucleotide phosphodiesterase. Altering seven lysine or four arginine residues resulted in two proteins whose activation properties on adenylate cyclase and phosphodiesterase had been modified in a way suggesting that lysine and arginine residues play distinct roles in the interaction of native calmodulin with each enzyme.
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PMID:The activation of brain adenylate cyclase and brain cyclic-nucleotide phosphodiesterase by seven calmodulin derivatives. 624 45

The adenylate cyclase of Bordetella pertussis is stimulated 100- to 1000-fold in a dose-dependent manner by calf brain calmodulin. The system has the following properties. (i) The activation is prevented by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and restored by Ca2+. (ii) Oxidation of the methionine residues of calmodulin abolishes the ability to activate the cyclase. (iii) Trifluoperazine inhibits calmodulin-activated cyclase. (iv) A troponin C preparation stimulates the B. pertussis cyclase with < 0.01 the potency of calmodulin. Although calmodulin has not been demonstrated in prokaryotes, this is an example of a (eukaryotic) calmodulin effect in a prokaryote.
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PMID:Calmodulin activates prokaryotic adenylate cyclase. 625 92

Three sulfur-free analogues of bovine parathyroid hormone (bPTH) containing D-amino acids were synthesized by the solid-phase method and their biological properties compared in an in vitro bioassay (rat renal adenylate cyclase assay), a receptor assay for parathyroid hormone (PTH) (canine renal membranes), and an in vivo bioassay (chick hypercalcemia assay). The analogue [Nle8,Nle18,D-Tyr34]-bPTH-(1-34)-amide, which was found to be more than 4 times as potent in vitro as unsubstituted PTH, is the most potent analogue of PTH yet synthesized. The enhanced potency was largely attributable to increased affinity for the PTH receptor. In vivo, however, this analogue was only one-third as potent as bPTH-(1-34). Cumulative evidence suggests that the nearly 15-fold decline in the relative potency when the compound was assayed in vivo is due to the substitution of norleucine for methionine. The other analogues, [D-Val2,Nle8,D-Tyr34]bPTH-(1-34)-amide and [D-Val2,Nle8,Nle18,D=Tyr34]bPTH-(2-34)-amide, were only weakly active in vitro and in vivo, indicating that substitution with D-amino acids at the NH2 terminus of PTH causes markedly diminished receptor affinity. In fact, the placement of a D-amino acid at the NH2 terminus is more deleterious to biological activity than is omission of amino acids at positions 1 and 2.
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PMID:Sulfur-free parathyroid hormone analogues containing D-amino acids: biological properties in vitro and in vivo. 627 93

alpha-Melanocyte-stimulating hormone (alpha-melanotropin; alpha-MSH) is a linear tridecapeptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) that reversibly darkens amphibian skins by stimulating melanomsome (pigment granule) dispersion within melanophores. By using a number of in vitro melanocyte assays, we have examined the conformational requirements for alpha-MSH activity. Synthesis of [half-Cys4,half-Cys10]-alpha-MSH, a cyclic, conformationally restricted, "isosteric" analogue of alpha-MSH, provided a melanotropin with a potency greater than 10,000 times that of the native hormone in stimulating frog (Rana pipiens) skin darkening. The cyclic analogue also showed substantially prolonged activity relative to the native hormone. [half-Cys4,half-Cys10]-alpha-MSH was approximately 30 times more potent than alpha-MSH in stimulating lizard (Anolis carolinensis) skin melanophores in vitro. By using a cell-free Cloudman S-91 mouse melanoma plasma membrane preparation, we found the cyclic analogue to be approximately 3 times as potent as the native hormone in stimulating adenylate cyclase activity. These results provide insight into the conformational requirements for biological activity of alpha-MSH, and the comparative conformational requirements of alpha-MSH at a number of pigment cell receptors.
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PMID:[half-Cys4,half-Cys10]-alpha-Melanocyte-stimulating hormone: a cyclic alpha-melanotropin exhibiting superagonist biological activity. 628 85


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