Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Guanylate cyclase activity decreased during the division phase of heat-shock synchronized Tetrahymena pyriformis, strain GL. However, when Ca2+ was removed by EGTA to negate the effects of the Ca2+-binding protein (calmodulin), which is required for the full activity of guanylate cyclase in this organism, no significant change in the enzymatic activity was observed throughout the cell cycle. On the other hand, the reduced guanylate cyclase activity at division phase was associated with a decreased level of calmodulin content. These results suggest that fluctuations in guanylate cyclase activity during the cell cycle would be dependent on the concentration of calmodulin.
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PMID:Cell cycle-associated changes of guanylate cyclase activity in synchronized Tetrahymena: a possible involvement of calmodulin in its regulation. 611 41

Six weeks following complete unilateral surgical isolation of the rat caudate nucleus, activation of adenylate cyclase was reduced in response to dopamine (DA), norepinephrine (NE), 5' -guanylyl-imidodiphosphate [Gpp(NH)p], DA + Gpp(NH)p, and NaF. The low Km form of cyclic AMP phosphodiesterase was elevated in the isolated side when compared to the intact caudate. No changes in activities of guanylate cyclase or in high Km cyclic AMP phosphodiesterase (with or without the calcium-dependent regulator protein, calmodulin or CDR) were observed between the control and isolated caudate. Histologically, the neural damage to the isolated caudate was principally confined to reduced numbers of dendritic spines of the remaining intrinsic caudate neurons.
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PMID:Attenuation of catecholamine-coupled adenylate cyclase following surgical isolation of rat caudate. 612 17

Chlorpromazine, when incubated with isolated adrenal cells, inhibited the ACTH-stimulated formation of cGMP and corticosterone production. It also inhibited the ACTH-stimulated membrane guanylate cyclase, but did not affect the binding of ACTH to the membrane receptors. cGMP-induced steroidogenesis was not affected by the drug. These data indicate that chlorpromazine interferes with adrenal steroid metabolism at a site between the hormone receptor and guanylate cyclase and also show that guanylate cyclase is composed of separate receptor and catalytic components. Furthermore, based on the premise that chlorpromazine exerts its inhibitory action by blocking the binding of a calcium receptor protein, such as calmodulin, to the receptor-coupled guanylate cyclase, it is proposed that the interaction of calcium, presumably through a calcium-binding protein, is essential for ACTH-dependent guanylate cyclase.
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PMID:Relationship of calcium and membrane guanylate cyclase in adrenocorticotropin-induced steroidogenesis. 612 29

The membraneous guanylate cyclase of cilia from Paramecium tetraurelia used MgGTP and MnGTP as substrate with Michaelis constants for GTP of 71.5 microM and 36 microM, respectively. A linear Arrhenius plot indicated that a single enzyme entity exists not sensitive to possible phase transitions of membrane lipids. Guanylate cyclase is activated by low concentrations (less than 100 microM) and inhibited by high concentrations (greater than 100 microM) of calcium, half-maximal effects were obtained with 8 microM and 500 microM Ca2+, respectively. Only strontium ions displayed partial activating and inhibiting potency, all other divalent cations tested, Ba2+, Fe2+, Co2+, Mn2+, Sn2+ and Ni2+ had no effect on guanylate cyclase activity. Ca2+ activation increased V; Km remained identical. The Ca2+ stimulated activity was not inhibited by trifluoperazine, tentatively suggesting that the stimulation may not be mediated by calmodulin. Ca2 inhibition was due to a single binding site of Ca2+ at the guanylate cyclase as evidence by a Hill coefficient h = -1 and was noncompetitive. The lanthanides La3+, Ce3+ and Tb3+ were powerful inhibitors of guanylate cyclase, with La3+ the half-maximal effect was obtained with 0.6 microM, it was kinetically a mixed-type inhibition. La3+ and CA2+ competed for the same binding site on the guanylate cyclase as determined by detailed kinetic analysis. Addition of EDTA reversed the activation and inhibition by Ca2+ and the inhibition by La3+. It is discussed that guanylate cyclase may be the initial target enzyme in the cilia for the calcium transient of the calcium-potassium action potential of Paramecium.
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PMID:Characterization of a Ca2+-dependent guanylate cyclase in the excitable ciliary membrane from Paramecium. 612 19

Phospholipid composition of Tetrahymena plasma membranes was modified by phospholipase A2-treatment and its effects on the activities of the two membrane-bound cyclases (adenylate and guanylate) were studied. Phospholipase A2 from Crotalus adamanteus was found to hydrolyze preferentially phosphatidylethanolamine of isolated plasma membranes. In the phospholipase A2-treated membranes in which 45% of total phosphatidylethanolamine was converted to its lysolipid, adenylate cyclase activity was to a small extent reduced, whereas guanylate cyclase activity was decreased almost to a half. However, the stimulation rate of the guanylate cyclase activity by calmodulin was unaffected in phospholipase A2-treated plasma membranes. The apparent Km value for substrates was not different between phospholipase A2-untreated and -treated plasma membranes. The ESR analysis demonstrated that the phospholipase A2-treated plasma membranes showed an increased fluidity in the range above 25 degrees C as compared to the untreated control membranes. These results suggest that guanylate cyclase is more dependent on phospholipid environment than adenylate cyclase in Tetrahymena plasma membranes, presumably offering evidence for the different location of two enzymes in the membrane.
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PMID:Differential inhibitory effects by phospholipase A2 on guanylate and adenylate cyclases of Tetrahymena plasma membranes. 612 36

Guanylate cyclase [EC 4,6,2,1] was found to be localized principally in the surface membrane (pellicle) of Tetrahymena pyriformis and to some extent in cilia, mitochondria and microsomes. In the pellicle fraction, guanylate cyclase activity with Mn2+ was higher than that with Mg2+. Addition of calmodulin and Ca2+ to the reaction mixture resulted in marked activation of guanylate cyclase with Mg2+ and Mn2+, but the extent of enhancement by calmodulin was greater with Mg2+ than with Mn2+. The activated enzyme could use either Mg2+ or Mn2+ as an equipotent cofactor.
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PMID:Calmodulin alters the cation requirement of membrane-bound guanylate cyclase in Tetrahymena. 612 37

Effect of a novel compound, 14-ethoxycarbonyl-(3 alpha, 16 alpha-ethyl)-14,15-eburnamenine (vinpocetine, TCV-3B), on the cyclic nucleotide metabolism and in vitro response of a vascular strip was investigated. The concentration of vinpocetine producing relaxation of the canine basilar arterial strip induced by 30 microM arachidonate peroxide was 3 microM. Cyclic GMP content in the vascular strip increased dose-dependently by addition of vinpocetine, and 2.5-fold elevation of cyclic GMP content in the vascular strip was observed by 10 microM vinpocetine. Administration of vinpocetine concentrations ranging from 1 to 100 microM did not produce a significant increase in cyclic AMP of the vascular strip. Vinpocetine did not stimulate guanylate cyclase, but selectively inhibited Ca2+-calmodulin dependent phosphodiesterase (Ca2+-PDE). Increase in cyclic GMP by vinpocetine is due to inhibition of Ca2+-PDE because Ca2+-PDE is known to hydrolyze cyclic GMP preferentially. Our results suggest that vinpocetine, a selective Ca2+-PDE inhibitor, produces relaxation of the vascular strip by the increase in cyclic GMP.
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PMID:[Effect of vinpocetine (TCV-3B), a vasodilator agent, on cyclic nucleotide metabolism]. 613 34

Trifluoperazine was shown previously to inhibit the activation of Tetrahymena guanylate cyclase activity by calmodulin [S. Nagao, S. Kudo and Y Nozawa, Biochem. Pharmac. 19, 2709 (1981)]. The present paper reports that N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), another representative calmodulin inhibitor, inhibited the calmodulin-induced activation of the guanylate cyclase, and that trifluoperazine and W-7 also inhibited Tetrahymena adenylate cyclase. The adenylate cyclase activity was found to be present in a membrane-bound form and not to be influenced by calmodulin. The inhibitions of the adenylate cyclase activity by these agents were dose-dependent and not Ca2+-dependent. These findings suggest that the inhibitory actions of these drugs may not necessarily be specific for calmodulin-dependent enzymes in T. pyriformis.
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PMID:Inhibitory effects of calmodulin antagonists on plasma membrane cyclases in Tetrahymena: calmodulin-dependent guanylate cyclase and calmodulin-independent adenylate cyclase. 613 22

Ca2+-regulated guanylate cyclase in ciliary membranes from Paramecium contained tightly bound calmodulin. Antisera against calmodulin from Tetrahymena and soybean inhibited enzyme activity. EGTA did not easily release calmodulin; however, La3+ inhibited guanylate cyclase by dissociation of calmodulin. While La could not replace Ca in the activation of guanylate cyclase, it substituted for Ca2+ in the activation of calmodulin-dependent phosphodiesterase from pig brain independently of whether homologous or Paramecium calmodulin was used. After removal of endogenous calmodulin from guanylate cyclase, reconstitution was achieved with calmodulin from Paramecium, Tetrahymena, pig brain, and soybean. Ca2+-binding proteins lacking trimethyllysine like calmodulin from Dictyostelium, parvalbumin, and troponin C failed to restore enzyme activity. The properties of the native and reconstituted guanylate cyclase/calmodulin complex were compared. Reassociation of calmodulin with its target enzyme was weak since all calmodulin remained in the supernatant after a single centrifugation. While most enzyme characteristics remained unchanged in the reconstituted complex, the inhibition by Ca greater than 100 microM was of a mixed-type compared to noncompetitive inhibition in the native enzyme. The regulation of the enzyme by cations was also altered. Whereas Ca was the most potent and specific activator of the native enzyme, in the reconstituted system Sr was far more effective.
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PMID:Calcium/calmodulin-regulated guanylate cyclase of the excitable ciliary membrane from Paramecium. Dissociation of calmodulin by La3+: calmodulin specificity and properties of the reconstituted guanylate cyclase. 613 52

A highly purified preparation of Tetrahymena calmodulin activated a membrane-bound guanylate cyclase by more than 40-fold. This activation of guanylate cyclase by calmodulin was inhibited completely by local anesthetics such as dibucaine, tetracaine, lidocaine and procaine at concentrations that had no appreciable effect on the activities of basal guanylate cyclase (without calmodulin) and adenylate cyclase. The inhibition by dibucaine of calmodulin-mediated activation of the enzyme activity was not reversed by calcium but was partially overcome by increasing the concentration of calmodulin. Kinetic analysis of local anesthetic-induced inhibition of activation of guanylate cyclase demonstrated a mixed type of antagonism. These results suggest the possibility that the inhibition of calmodulin-dependent guanylate cyclase resulted, in part, from interaction of the drugs with calmodulin.
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PMID:Effects of local anesthetics on calmodulin-dependent guanylate cyclase in the plasma membrane of Tetrahymena pyriformis. 614 14


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