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)

1. Membrane currents were recorded from voltage-clamped Xenopus oocytes in response to bath application of various divalent cations. 2. In oocytes from 93 of 160 frogs tested, Co2+ ions evoked slow, oscillatory membrane currents. Sensitivity to Co2+ varied greatly between oocytes from different frogs, but was relatively consistent for oocytes taken from the same ovary. Oocytes with high sensitivity had response thresholds of 5-10 microM, and gave currents greater than 1 microA to 1 mM-CoCl2. In contrast, oocytes from some frogs gave no oscillatory response even to 10 mM-CoCl2. With responsive oocytes, Cd2+, Ni2+, Zn2+, Mn2+ and Cr2+ ions (5 microM to 1 mM) also elicited oscillations, whereas Sr2+, Ba2+ and Ca2+ (0.1-10 mM) showed very little activity, and Mg2+ ions, none. 3. Responses to divalent cation were well preserved in defolliculated oocytes, indicating they were generated in the oocyte membrane itself, and were not dependent on the presence of enveloping follicular cells. 4. The oscillatory currents reversed around -20 mV (the chloride equilibrium potential) and rectified strongly at potentials more negative than about -60 mV. The oscillations were mimicked by intraoocyte injection of inositol 1,4,5-trisphosphate (IP3), were largely preserved after removal of external Ca2+, but were abolished following chelation of intracellular Ca2+ by EGTA. Intraoocyte injection of Co2+ ions failed to generate oscillatory currents. 5. Currents elicited by divalent cations resembled the oocyte's oscillatory responses to acetylcholine and a serum protein. However, the response to divalent cations was not blocked by atropine and furthermore, the relative sensitivities to these agonists varied independently between oocytes from different frogs. 6. We conclude that extracellular Cd2+, Ni2+, Zn2+, Co2+, Mn2+ and Cr2+ interact with the oocyte surface to raise cytosolic levels of inositol phosphates. This causes mobilization of intracellular Ca2+, in turn activating Ca2+-gated Cl- channels in the oocyte membrane. 7. In addition to the large oscillatory currents, divalent cations generated small (5-50 nA), smooth, maintained currents associated with decreases in membrane conductance. The size and ionic basis of these currents varied between oocytes from different frogs. 8. Zinc ions also elicited smooth currents, associated with an increase in membrane conductance, and carried predominantly by K+. This response was specific to Zn2+ and occurred independently of oscillatory Cl- currents. The K+ current was abolished by defolliculation, was potentiated by the cyclic AMP phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine,and showed facilitation with K+ currents generated by the adenylate cyclase activator forskolin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Membrane currents elicited by divalent cations in Xenopus oocytes. 248 82

The small proteoglycans (PG) of bone consist of two different molecular species: one containing one chondroitin sulfate chain (PG II) and the other, two chains (PG I). These two proteoglycans are found in many connective tissues and have Mr = 45,000 core proteins with clear differences in their NH2-terminal sequences. Using antisera produced against synthetic peptides derived from the human PG I and PG II NH2 termini, we have isolated several cDNA clones from a lambda gt11 expression library made against mRNA isolated from human bone-derived cells. The clones, which reacted with antisera to the PG II peptide, were sequenced and found to be identical with the PG II class of proteoglycan from human fibroblasts known as PG-40 or decorin. The clones reacting to the PG I antisera, however, had a unique sequence. The derived protein sequence of PG I showed sufficient homology with the PG II sequence (55% of the amino acids are identical, with most others involving chemically similar amino acid substitutions) to strongly suggest that the two proteins were the result of a gene duplication. PG II (decorin) contains one attached glycosaminoglycan chain, while PG I probably contains two chains. For this reason, we suggest that PG I be called biglycan. The biglycan protein sequence contains 368 residues (Mr = 42,510 for the complete sequence and Mr = 37,983 for the secreted form) that appears to consist predominantly of a series of 12 tandem repeats of 24 residues. The repeats are recognized by their conserved leucines (and leucine-like amino acids) in positions previously reported for a diverse collection of proteins (none of which is thought to be proteoglycans) including: two morphogenic proteins (toll and chaoptin) in the fruit fly; a yeast adenylate cyclase; and two human proteins, the von Willebrand Factor-binding platelet membrane protein, GPIb, and a rare serum protein, leucine-rich glycoprotein.
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PMID:Deduced protein sequence of bone small proteoglycan I (biglycan) shows homology with proteoglycan II (decorin) and several nonconnective tissue proteins in a variety of species. 264 39

Several thyroid hormone binding inhibitors have been described in nonthyroid illness. One of the major inhibitors, oleic acid, is present in excess amounts in sera of patients with nonthyroid illness. In this study, we demonstrated that oleic acid inhibited the cAMP accumulation of thyroid plasma membrane activated by thyrotropin at 50 mumol/l and higher concentrations. In the presence of albumin, oleic acid significantly inhibited the cAMP accumulation of plasma membrane activated by thyrotropin at 2.4 mmol/l (P less than 0.01 when the albumin concentration was 40 g/l and pH was 7.4; P less than 0.001 when the albumin concentration was 20 g/l and pH was 7.2). These findings suggest that in nonthyroid illness, especially at a low albumin concentration and low blood pH, a high oleic acid concentration may influence the thyroid function directly in addition to inhibiting the thyroid hormone binding to serum protein. Oleic acid also could inhibit 5'-guanylylimidodiphosphate- and forskolin-induced cAMP production in thyroid plasma membranes. Therefore, the inhibiting effect of oleic acid may be through the action of oleic acid on the catalytic unit of the hormone-sensitive adenylate cyclase system.
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PMID:The influence of oleic acid on cAMP accumulation of thyroid plasma membrane activated by thyrotropin. 283 81

Activity of autoantibodies to the thyrotropin receptor in the serum of patients with active Graves's disease was compared when the patients' IgG was purified by three different procedures: ammonium sulfate precipitation (I), a modified batch diethylaminoethyl cellulose method (II), and affinity chromatography on Protein A-Sepharose CL-4B (III). IgG extracted by I was significantly less potent in inhibiting binding of 125I-labeled thyroid membranes than that prepared by either II or III, and was significantly less effective than II in stimulating adenyl cyclase activity in thyroid membrane. Thyroglobulin, a serum protein whose concentration is increased in patients with various thyroid diseases, was coprecipitated in amounts sufficient to significantly inhibit binding only when method I was used, but not with either of the other two procedures. Evidently method I is inferior to either of the other two when used for purification of autoantibodies to the thyrotropin receptor. Method II used in this study, being faster and more economical than I and of equivalent efficacy, is a feasible alternative method for clinical use.
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PMID:Choice of immunoglobulin G purification method in assays for antibodies to the thyrotropin receptor. 287 56