Increased inhibitory action against adenosine 5'-triphosphate in the isolated taenia of the guinea-pig caecum by substitution in the A-ring of 2-phenylisatogen.
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1 The ability of a series of 17 isatogen derivatives to relax smooth muscle, inhibit adenosine 5'-diphosphate (ADP)-stimulated respiration in isolated mitochondria and to antagonize the inhibitory effects of adenosine 5'-triphosphate (ATP) on smooth muscle was measured. 2 Substitution in the 4- and 7-positions of the A-ring gave compounds that were strong inhibitors of mitochondrial ATP synthesis and potent, non-specific smooth muscle relaxants. The compounds also possessed ATP-receptor blocking activity. 3 Substitution in the 5- and 6-positions of the A-ring decreased both the relaxant effect on smooth muscle and inhibition of ATP synthesis, whilst enhancing ATP-receptor antagonism. 4 In a series of 6-substituted 2-phenylisatogens, 6-methoxy-2-phenylisatogen was the most effective ATP-receptor antagonist. This compound also showed the greatest separation of the desired pharmacological activity (ATP-receptor blockade) from the other two activities (smooth muscle relaxation and inhibition of mitochondrial ATP synthesis). (+info)
The mechanism of the relaxant effect of 2-2'-pyridylisatogen on the isolated taenia of the guinea-pig caecum.
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1 2-2'-Pyridylisatogen tosylate (PIT) slowly relaxed taenia caeci preparationg of the guinea-pig in a concentration-dependent manner (threshold 2.5 muM). The relaxant effect did not show tachyphylaxis.2 The relaxation was not affected by tetrodotoxin (0.3 muM), guanethidine (17 muM) nor by a combination of phentolamine (36 muM) and propranolol (4 muM)3 In taenia caeci preparations suspended in K(+)-depolarizing, Ca(2+)-free Ringer, addition of Ca(2+) (0.1 to 30 mM) resulted in a slow contraction. PIT (50 muM) and papaverine (15 muM) antagonized these contractions, whereas indomethacin (28 muM) was ineffective.4 Although PIT (50 muM for 30 min) caused a relaxation of the taenia, and, when the tone of the preparations was restored with carbachol, antagonized adenosine 5'-triphosphate (ATP)-induced relaxations, relaxation of the taenia with papaverine (30 muM for 5 min) did not antagonize ATP-induced relaxations. It is concluded that the relaxant and ATP-receptor blocking actions of PIT are independent properties of the compound. (+info)
Formation of vaccinia virus DNA-protein complex in the presence of isatin beta thiosemicarbazone (IBT).
(75/87)
The association of newly synthesized vaccinia virus DNA with proteins in infected HeLa cells was followed. A shift from a high density to a low density complex occurred between 3 and 6 h after infection. This process was not affected by isatin beta thiosemicarbazone (IBT), an inhibitor of pox virus growth. At 22 h after infection in the absence of IBT, mature virions of high density were observed; however, in the presence of the drug, high density DNA-protein complexes, which lack the two main virus core polypeptides, were formed. (+info)
The effects of vasoactive intestinal polypeptide and of adenosine 5'-triphosphate on the isolated anococcygeus muscle of the mouse.
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1 Vasoactive intestinal polypeptide (VIP, 0.01- MicroM) produced dose-related relaxations of the mouse anococcygeus muscle. 2 Following incubation with indomethacin (2.8 microM 1 h) adenosine 5'-triphosphate (ATP, 0.5-10 mM) produced dose-related relaxations of the mouse anococcygeus. 3 Haemolysed blood reduced inhibitory responses of the mouse anococcygeus to field stimulation but had no effect on relaxations to VIP or ATP. 4 Apamin (0.5 microM) had no effect on the relaxation of mouse anococcygeus to field stimulation, VIP, or ATP. 5 2-2'-Pyridylisatogen tosylate (PIT, 50 microM) itself reduced muscle tone but it did not abolish inhibitory responses to field stimulation, VIP, or ATP. 6 During prolonged inhibitory nerve stimulation the relaxation of the mouse anococcygeus in response to VIP was reduced greatly while that to ATP was unaffected. 7 Bundles of VIP-immunoreactive sites were detected in sections of the mouse anococcygeus treated by the peroxidase-antiperoxidase (PAP) immunocytochemical technique. 8 The results suggest that the mechanisms underlying non-adrenergic, non-cholinergic inhibitory transmission in the mouse anococcygeus are similar to those in the bovine retractor penis and unlike those in the guinea-pig taenia caeci. 9 The possibility that VIP or ATP might be involved in inhibitory neurotransmission in the mouse anococcygeus is discussed. (+info)
Catabolism of indole-3-acetic acid and 4- and 5-chloroindole-3-acetic acid in Bradyrhizobium japonicum.
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Some strains of Bradyrhizobium japonicum have the ability to catabolize indole-3-acetic acid. Indoleacetic acid (IAA), 4-chloro-IAA (4-Cl-IAA), and 5-Cl-IAA were metabolized to different extents by strains 61A24 and 110. Metabolites were isolated and analyzed by high-performance liquid chromatography and conventional mass spectrometry (MS) methods, including MS-mass spectroscopy, UV spectroscopy, and high-performance liquid chromatography-MS. The identified products indicate a novel metabolic pathway in which IAA is metabolized via dioxindole-3-acetic acid, dioxindole, isatin, and 2-aminophenyl glyoxylic acid (isatinic acid) to anthranilic acid, which is further metabolized. Degradation of 4-Cl-IAA apparently stops at the 4-Cl-dioxindole step in contrast to 5-Cl-IAA which is metabolized to 5-Cl-anthranilic acid. (+info)
Formation of indigo and related compounds from indolecarboxylic acids by aromatic acid-degrading bacteria: chromogenic reactions for cloning genes encoding dioxygenases that act on aromatic acids.
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The p-cumate-degrading strain Pseudomonas putida F1 and the m- and p-toluate-degrading strain P. putida mt-2 transform indole-2-carboxylate and indole-3-carboxylate to colored products identified here as indigo, indirubin, and isatin. A mechanism by which these products could be formed spontaneously following dioxygenase-catalyzed dihydroxylation of the indolecarboxylates is proposed. Indolecarboxylates were employed as chromogenic substrates for identifying recombinant bacteria carrying genes encoding p-cumate dioxygenase and toluate dioxygenase. Dioxygenase gene-carrying bacteria could be readily distinguished as dark green-blue colonies among other colorless recombinant Escherichia coli colonies on selective agar plates containing either indole-2-carboxylate or indole-3-carboxylate. (+info)
Inactivation of lambda phage infectivity and lambda deoxyribonucleic acid transfection by N-methyl-isatin beta-thiosemicarbazone-copper complexes.
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The infectivity of intact lambda phage and transfection by lambda deoxyribonucleic acid were inactivated by exposure to the copper complexes of N-methyl-isatin beta-thiosemicarbazone, thiosemicarbazide, and semicarbazide, but not methyl-isatin. No inactivation was observed when these compounds were used in the absence of copper sulfate. This confirms our previous observation that the activity of N-methyl-isatin beta-thiosemicarbazone is mediated by its thiosemicarbazone moiety and that the presence of copper is required for action. This represents the first time, to our knowledge, that semicarbazide has been found to possess antiviral activity. It is clear that these compounds act directly on deoxyribonucleic acid; whether the compounds also act on proteins has not been determined. (+info)
Arenavirus inactivation on contact with N-substituted isatin beta-thiosemicarbazones and certain cations.
(80/87)
N-methyl and N-ethyl isatin beta-thiosemicarbazones inactivate cell-free Parana and Pichinde viruses as well as three strains of lymphocytic choriomeningitis virus. This antiviral activity is abolished in the presence of the chelating agent EDTA. The rate of virus inactivation by N-methyl isatin beta-thiosemicarbazone is greatly enhanced and controlled by the addition of cupric sulphate. Divalent cations of other first transition series metals are less effective. A difference exists in the copper requirement for fast inactivation of the prototype arenavirus (lymphocytic choriomeningitis) and the Tacaribe Complex of viruses (Parana and Pichinde). In the presence of 20 muM-N-methyl isatin beta-thiosemicarbazone, LCM and Pichinde viruses can be inactivated at about the same rate if 20 muM-CuSO4 is added to the former and 160 muM-CuSO4 is added to the latter. Using 20 muM-N-methyl isatin beta-semicarbazone and CuSO4 the inactivation of LCM is reduced, but not eliminated, in the presence of an equal amount of infectious Pichinde virus. Crude and highly purified Pichinde virus are inactivated at the same rate when exposed to identical concentrations of N-methyl isatin beta-thiosemicarbazone and cupric sulphate. There is little detectable change in the inactivation rates when Pichinde or LCM viruses are grown in a variety of different cell lines. (+info)