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)

The existence of lipolytic beta-adrenoceptor (BAR) resistance was investigated in vivo and in isolated abdominal subcutaneous adipocytes in 65 healthy and drug-free subjects. The concentration of isoprenaline (nonselective BAR agonist) causing half-maximum lipolysis effect (ED50) varied bimodally and 10(6)-fold between individuals but was almost constant in the same subject when measured two times at rest or before and 30 min after exercise. The subjects were categorized as having either high or low isoprenaline sensitivity. The former group had a 50% reduced in vivo lipolytic response to exercise and mental stress, despite a 50% increased plasma noradrenaline response (P < 0.01) and a 350% increased plasma adrenaline response (P < 0.02). In fat cells the lipolytic ED50 values for noradrenaline and terbutaline (BAR2 agonist) were 10 times lower (P < 0.001) in low-sensitive subjects, but the maximum lipolytic actions of these agents (and of isoprenaline) were similar in both groups. The action on lipolysis of dobutamine (BAR1 agonist), forskolin (stimulating adenylate cyclase), dibutyryl cyclic AMP (activating protein kinase), clonidine (alpha 2-adrenergic agonist), or phenyl isopropyladenosine (adenosine receptor agonist) were almost identical in high- and low-sensitivity subjects. ED50 for isoprenaline correlated with ED50 for terbutaline (r = 0.75), but not with ED50 for dobutamine. In high-sensitivity subjects the number of BAR2 was almost three-fold increased (P < 0.002) and the steady-state adipocyte mRNA level for BAR2 was sixfold increased (P < 0.005). BAR2 affinity as well as BAR1 number, affinity and mRNA expression were similar in both groups. In 11 cholecystectomy patients (otherwise healthy) lipolytic ED50 for beta agonists correlated in omental and subcutaneous fat cells (r = 0.85 for isoprenaline; r = 0.95 for terbutaline). In conclusion, lipolytic resistance to catecholamines is present in vivo in apparently healthy subjects due to reduced expression of BAR2 in adipocytes.
 ...
PMID:Lipolytic catecholamine resistance due to decreased beta 2-adrenoceptor expression in fat cells. 133 70

The pharmacological and gene expressions of beta 1- and beta 2-adrenoceptor subtypes (BAR1 and BAR2) were investigated in human liver by radioligand binding assays, adenylate cyclase experiments, and RNA excess solution hybridization. [125I]Cyanopinodolol, nonlabeled adrenergic agents, and BAR1/BAR2 cRNA were used as probes. The relationship between binding sites for BAR1 and BAR2 was markedly different from that between the basal mRNA expression for the two receptor subtypes. Plasma membranes as well as a microsomel-enriched fraction contained binding sites only for BAR2. The potency of BAR agonists and antagonists in stimulating adenylate cyclase activity of plasma membranes was typical of a BAR2 response. Northern blot analysis of total cellular RNA isolated from liver tissue showed hybridization of the BAR1 probe to a mRNA species of 2.5-2.6 kilobases and of the BAR2 probe to a mRNA species of 2.2-2.3 kilobases. The basal level of BAR1 mRNA was 5-fold higher than of BAR2 mRNA, as assayed by solution hybridization. No difference in BAR subtype mRNA stability was observed, as indicated by a mRNA half-life of approximately 5.5 h for both receptor subtypes. It is concluded that specific factors are involved in the steady state regulation of BAR subtype expression in human liver. This tissue contains solely BAR2 owing to a posttranscriptional block of basal BAR1 expression.
 ...
PMID:Beta-adrenoreceptor subtype expression in human liver. 217 70