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)

beta-Adrenergic blockers are less efficacious as monotherapy for the treatment of hypertension in blacks as compared with whites. Because beta-adrenergic stimulation and blockade differ between racial groups, biochemical differences in the beta-adrenergic pathway may exist. It is the intent of this report to show underlying similarities and differences, at least in part, in the beta-adrenergic pathway (e.g., baseline cAMP and protein concentrations) using the T-lymphocyte as the model system. A total of 20 (n = 10 black, n = 10 white) normotensive male volunteers were recruited, begun on a low-sodium diet to normalize serum catecholamines, and blood was collected for lymphocyte beta-receptor isotherm binding experiments and cAMP determination. There were no differences in Bmax, sites per cell, or kd. Basal cAMP concentrations were significantly higher in the black group (16.0 +/- 9.8 pmol/10(6) cells) compared with the white group (7.0 +/- 1.8 pmol/10(6) cells) (p less than 0.05). Protein levels from the lymphocyte suspension were also higher in the black group (1,081.0 +/- 367.7 micrograms/ml) compared with the white group (766.8 +/- 220.4 micrograms/ml) (p less than 0.05). Normalization of cAMP for protein yielded 83.2 +/- 55.4 fmol/micrograms protein in the black group and 56.6 +/- 29.8 fmol/micrograms protein in the white group (p = 0.11). Altered protein levels may be a confounding variable in studies of this type. Further work is necessary to identify the nature and significance of this protein elevation, its relationship to the adenylate cyclase system in lymphocytes, and the source of the cAMP elevation noted herein.
Ther Drug Monit 1990 Nov
PMID:Racial differences in baseline cyclic adenosine monophosphate concentrations per million T-lymphocytes and protein concentrations. 198 Mar 84

The coupling of the muscarinic receptor to the inhibition of the adenylate cyclase system was studied in adult rat cortical tissue dissociated by teasing tissue minces through finely meshed Nitex filters. The intracellular ATP stores in the final preparation were metabolically prelabeled with [3H]adenine and the [3H]cAMP formed in the tissue was isolated by ion exchange chromatography. Forskolin (3-30 microM) elevated [3H]cAMP levels 5- to 9-fold over basal in the preparation, with maximum stimulation achieved by 10-15 min. In the dissociated cortex, carbachol inhibited forskolin-elevated [3H]cAMP levels with an EC50 value of 1.4 microM; maximal inhibition was in the range of 20-30%. Atropine completely blocked the response (Ki = 1.8 nM), which showed that carbachol stimulates a muscarinic receptor to inhibit [3H]cAMP levels in this preparation. Pirenzepine, an M1-selective antagonist, blocked the response to carbachol with low potency (Ki = 467 nM), which indicated that an M2 muscarinic receptor subtype mediates [3H]cAMP inhibition in the cortex. The response to 10 microM carbachol was not affected by 10 mM EGTA, 50 microM D-tubocurarine, or 100 nM tetrodotoxin; thus, activation of nicotinic receptors or a neuronal release process was not involved. [3H]cAMP reduction in response to muscarinic stimulation was also observed in dissociated tissue prepared from other brain regions. A robust response was encountered in striatal preparations (maximal inhibition 40%), while hippocampal responses were smaller and less reproducible than in the cortex. The striatal response was shown to be pharmacologically similar to the cortical response.
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PMID:Muscarinic M2 receptor-mediated cyclic AMP reduction in mechanically dissociated rat cortex. 285 Aug 35

To identify any differences in inhibitory G protein (Gi) attributable to species or the cause of heart failure, we studied the changes in this protein in different animal models of heart failure: 1) different species; rats vs. hamsters (F1B) with cardiomyopathy induced by adriamycin (ADR) and 2) different etiologies; rats with ischemic heart failure (IHD) due to coronary artery ligation vs. rats with cardiomyopathy induced by ADR and F1B (20-week-old) hamsters with cardiomyopathy induced by ADR vs Syrian hamsters BIO 14.6 (40-week-old) with genetic cardiomyopathy, using Western blotting methods and ADP-ribosylation. We also sought to determine whether changes in the amount of Gi protein reflected the regulation of adenylate cyclase. The amount of immunodetectable Gi rose by 35% (p < 0.05) in ADR rats, 25% (p < 0.05) in ADR hamsters, 15% (p < 0.05) in IHD rats, and 28% (p < 0.05) in BIO 14.6 hamsters, as compared with control rats, F1B (20-week-old) hamsters, sham-operated control rats, and F1B (40-week-old) hamsters, respectively. Assessment of Gi by pertussis toxin-catalyzed ADP-ribosylation revealed increases in Gi of 24% (p < 0.05) in ADR rats and of 44% (p < 0.05) in BIO 14.6 hamsters, as compared with their respective controls. Gi function, as assayed by the acetylcholine-induced inhibition of adenylate cyclase, also increased. Thus, Gi protein appears to contribute to the changes in signal transduction in myocardium with heart failure.
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PMID:Increased levels of inhibitory G protein in myocardium with heart failure. 769 38