Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dictyostelium contains two guanylyl cyclases, GCA, a 12-transmembrane enzyme, and sGC, a homologue of mammalian soluble adenylyl cyclase. sGC provides nearly all chemoattractant-stimulated cGMP formation and is essential for efficient chemotaxis toward cAMP. We show that in resting cells the major fraction of the sGC-GFP fusion protein localizes to the cytosol, and a small fraction is associated to the cell cortex. With the artificial substrate Mn2+/GTP, sGC activity and protein exhibit a similar distribution between soluble and particulate fraction of cell lysates. However, with the physiological substrate Mg2+/GTP, sGC in the cytosol is nearly inactive, whereas the particulate enzyme shows high enzyme activity. Reconstitution experiments reveal that inactive cytosolic sGC acquires catalytic activity with Mg2+/GTP upon association to the membrane. Stimulation of cells with cAMP results in a twofold increase of membrane-localized sGC-GFP, which is accompanied by an increase of the membrane-associated guanylyl cyclase activity. In a cAMP gradient, sGC-GFP localizes to the anterior cell cortex, suggesting that in chemotacting cells, sGC is activated at the leading edge of the cell.
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PMID:Activation of soluble guanylyl cyclase at the leading edge during Dictyostelium chemotaxis. 1560 98

The membrane-bound atrial natriuretic peptide receptor (GCA) catalyzes the formation of cGMP from GTP in response to natriuretic peptide hormones. Previous structural studies have focused on the extra-cellular hormone binding domain of this receptor whereas its intra-cellular domain has not yet been amenable to such studies. We report here the baculovirus expression and purification of the GCA intra-cellular domain construct GCA(ID) comprising the complete intra-cellular region which includes the kinase-homology domain, coiled-coil region, and catalytic cyclase domain. The intra-cellular domain was enzymatically characterized in terms of guanylyl cyclase activity and the effects of ATP, manganese, and Triton X-100. Our results indicate that the activity of the intra-cellular domain of the ANP receptor is about 2 fold less active compared to a truncated cyclase domain construct lacking the kinase-like domain that was also expressed and purified. In addition, unlike the full length receptor, the intra-cellular domain could not be activated by Triton X-100/Mn(2+) or its activity stimulated by ATP. These data therefore indicate that the major part of the transition from the basal state to the fully, ANP/ATP-dependent, activated state as well its stimulation/enhancement by Triton X-100/Mn(2+) requires the full length receptor. These receptor insights could aid in the development of novel therapeutics as the GCA receptor is a key drug target for cardiovascular diseases.
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PMID:Expression, purification, and characterization of the intra-cellular domain of the ANP receptor. 1939 86

The ligatation behaviour of sulphonylurea glibenclamide drug is studied in order to give an idea about its potentiality towards some transition metals in vitro systems. Metal complexes of glibenclamide (GCA; H(3)L) drug are prepared and characterized based on elemental analyses, IR, diffused reflectance, magnetic moment, molar conductance and thermal analysis (TG and DTG) techniques. From the elemental analyses data, the complexes are proposed to have the general formulae [M(H(3)L)Cl(n)(H(2)O)(m)].yH(2)O (where M=Cr(III) (n=3, m=1, y=3); Mn(II) (n=2, m=0, y=1); Fe(III) (n=3, m=1, y=0), Co(II) (n=2, m=2, y=0); Ni(II) (n=2, m=2, y=3); Cu(II) (n=2, m=2, y=2) and Zn(II) (n=2, m=0, y=0). The molar conductance data reveal that all the metal chelates are non-electrolytes. IR spectra show that GCA is coordinated to the metal ions in a neutral bidentate manner with OO donor sites of the amide-O and sulphone-O. From the magnetic and solid reflectance spectra, it is found that the geometrical structures of these complexes are octahedral except Mn(II) and Zn(II) complexes which have tetrahedral structure. The thermal behaviour of these chelates is studied using thermogravimetric analysis (TG and DTG) technique. The activation thermodynamic parameters are calculated using Coats-Redfern method. The GCA drug, in comparison to its metal complexes also is screened for its biological activity against house fly, Musca domestica (Diptera-Muscidae). Dose of 5 microg/insect of GCA is topically applied against 3 days old larval instar of M. domestica. Survival of pupal and adult stages has been affected by the complexes of GCA more than larval instars. Morphogenic abnormalities of larvae, pupae and adults are studied. On the other hand pupation and adult emergence program is deteriorated by the effect of different chemicals.
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PMID:Biological potential study of metal complexes of sulphonylurea glibenclamide on the house fly, Musca domestica (Diptera-Muscidae): preparation, spectroscopic and thermal characterization. 1967 29