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

Calmodulin is a protein with calcium-dependent binding sites. Binding of calcium ions induces changes in the conformation and activation of many enzymes such as adenylate cyclase, guanylate cyclase, ATPase. Neuroleptic drugs bind calmodulin. Trifluoperazine has a very high affinity for calmodulin. Tricyclic antidepressants and benzodiazepines also bind calmodulin. Binding of neuroleptics inhibits many biological phenomena such as lymphocyte endocytosis, platelets aggregation. When neuroleptics are administrated chronically, calmodulin could act in regulation of the receptors specially in the drug induced supersensitivity of striatum dopamine receptors. These experiments about the regulation of the receptors mediated by calmodulin have been performed ten years ago and their results were not confirmed later. Moreover, binding of calmodulin is not specific of neuroleptic drugs. The effects of neuroleptics on calmodulin, only observed in vitro or with animals, seem to be mainly related to structural properties of the drugs.
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PMID:Could the interaction of neuroleptics with calmodulin be an "explanation" of the psychotropic effects? 168 72

The present study, addressed to understand the mechanism behind the cholesterol-induced proliferative and collagen secretory activity of smooth muscle cells, revealed that cholesterol-induced smooth muscle cellular DNA synthesis and collagen secretion was mediated through its ability to amplify the intracellular cGMP signal because of the fact that Trifluoperazine (an anticalmodulin and blocker of phospholipase A2) and colchicine (an antitubulin and inhibitor of guanyl cyclase) inhibited DNA synthesis and collagen-secretory activity of smooth muscle cells by their ability to decrease the cGMP levels within smooth muscle cells. From these results we suggest that membrane cholesterol modulated phospholipase 'A2' activity may be the basic mechanism involved in cholesterol-induced proliferative and collagen-secretory activity of smooth muscle cells in vitro.
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PMID:Effect of trifluoperazine and colchicine on smooth muscle cellular proliferative and secretory activity induced by hypercholesterolemic medium in vitro. 216 85

We investigated the effects of fendiline, calmidazolium and trifluoperazine, compounds described as calmodulin antagonists, on the release of the endothelial autacoids prostacyclin (PGI2) and endothelium-derived relaxant factor (EDRF). Cultured bovine aortic endothelial cells were grown on microcarrier beads and continuously superfused with Tyrode's solution. Samples collected from the superfusate were assayed for PGI2 concentration (6-keto PGF1 alpha radioimmunoassay) and for EDRF activity (stimulation of soluble guanylate cyclase in vitro). Stimulation of endothelial cells by ATP (3 microM) resulted in a 6.9 +/- 1.4-fold increase of PGI2 concentration in the superfusate (p less than 0.01) and an 8.6 +/- 3.4-fold enhanced guanylate cyclase activity (p less than 0.01). In the presence of calmidazolium (10 microM), the basal values of PGI2 concentration increased 28-fold (p less than 0.01) and the guanylate cyclase activity 10-fold (p less than 0.01). Further enhancement of both was observed after additional administration of ATP. Fendiline (30 microM) did not affect autacoid release by non-stimulated cells. However, the ATP-induced release of PGI2 and EDRF was more than doubled (p less than 0.01) in the presence of this drug compared to ATP-stimulation alone. Trifluoperazine (10 microM) had no enhancing effect on EDRF release, and the ATP-induced release of PGI2 was even significantly attenuated by 84 +/- 12% (p less than 0.01). Calmidazolium and fendiline were also applied to endothelial cells loaded with the fluorescent indicator of free calcium concentration (Ca2i+), indo-1. However, effects of calmidazolium on Ca2i+ could not be quantified since calmidazolium caused some leakage of indo-1 out of the cells. A smaller leakage was observed during the combined application of fendiline and ATP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fendiline and calmidazolium enhance the release of endothelium-derived relaxant factor and of prostacyclin from cultured endothelial cells. 328 26

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