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)

Subacute cadmium treatment (CdCl2, 1 mg/kg twice daily for 7 days) in rats disturbs glucose homeostasis as shown by hyperglycemia and decreased glucose tolerance associated with suppression of insulin release, enhancement of hepatic gluconeogenic enzymes and decrease in hepatic glycogen content. 2 Exposure to cadmium increases hepatic cyclic adenosine 3',5'-monophosphate (cyclic AMP) and this is accompanied by stimulation of basal, adrenaline- as well as glucagon-stimulated form(s) of adenylate cyclase. 3 In contrast to cadmium, subacute administration of zinc (ZnCl2, 2 mg/kg twice daily for 7 days) fails to alter the activities of hepatic gluconeogenic enzymes, cyclic AMP synthesis, as well as glucose clearance and insulin release in response to a glucose load. 4 Zinc, when administered at the same time as cadmium, prevents the cadmium-induced lesions in both hepatic and pancreatic functions. 5 The results are discussed in relation to the possible mechanisms of cadmium toxicity and to the role of sulphydryl groups in the protection exercised by zinc.
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PMID:Prevention by zinc of cadmium-induced alterations in pancreatic and hepatic functions. 18 49

A method is reported for preparing surface (plasma) membranes from adrenal tumour (Y-1) cells. The procedure is based upon homogenization in hypotonic ZnCl2 followed by sedimentation through two sucrose density gradients. The purified membranes consist of large sheets of membrane. The identity and purity of the membranes was demonstrated by: (1) microscopy (phase contrast and electron); (2) enzyme markers; and (3) functional activities associated with plasma membranes (binding of ACTH and LDL and adenylate cyclase). Phase-contrast microscopy revealed the release of membrane ghosts free from cytoplasm and nuclei. Electron microscopy showed membranes with small fragments of cytoplasm attached to the inside. Binding of ACTH was found to be specific with KD 0.12 nM and the equivalent of 2500 sites per cell. Binding of LDL was also specific with KD 0.5 nM and the equivalent of 4800 sites per cell. Specific activities of binding for ACTH and LDL were increased by 21-fold and 15-fold, respectively, relative to whole homogenate. Membranes were also prepared from beef fasciculata cells by the same method.
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PMID:Plasma membranes from adrenal cells: purification and properties. 300 30

Numerous environmental xenobiotics can act as endocrine disrupters in wildlife species. Fish chronically exposed to pollutants exhibit a deficiency in the synthesis of cortisol, a glucocorticosteroid hormone secreted by interrenal steroidogenic cells in response to ACTH by a mechanism mediated by cAMP. The capacity of a series of heavy metals (CdCl2, ZnCl2, HgCl2, and CH3HgCl) and 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane (o,p'-DDD) to disrupt cortisol secretion was determined in dispersed interrenal cells of rainbow trout (Oncorhynchus mykiss) exposed in vitro to the toxicant, by measuring cortisol secretion stimulated with ACTH or dibutiryl-cAMP (dbcAMP) and by assessing cell viability. The effect of cadmium in presence of zinc on the interrenal cells was also determined. The median lethal concentration (LC50, dose that kills 50% of the cells), median effective concentration (EC50, dose that inhibits cortisol secretion by 50%), and LC50/EC50 ratio were determined for each chemical to compare its endocrine toxicity and to test the specificity of the toxicants to act as endocrine disrupters. HgCl2 had the lowest EC50 and LC50; it was the most toxic of the chemicals tested. The LC50/EC50 ratio was the highest for ZnCl2 and CdCl2, indicating that these toxicants had the most specific endocrine toxicity. The mechanism of toxicity of heavy metals on cortisol-secreting cells involves a site situated downstream from the step generating cAMP, while o,p'-DDD seemed to impair a step located between adenyl cyclase activation and the ACTH binding. No evidence for a protector effect of zinc against cadmium toxicity was found.
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PMID:Effects of in vitro exposures to cadmium, mercury, zinc, and 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane on steroidogenesis by dispersed interrenal cells of rainbow trout (Oncorhynchus mykiss). 1032 3