Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Formoterol and salbutamol were compared for in vitro inhibition of allergen-induced histamine release from allergic leukocytes and human lung tissue passively sensitized with allergic serum. Formoterol inhibited the release of histamine from leukocytes but salbutamol showed little inhibiting effect. When combined with theophylline, formoterol was a more potent inhibitor of the release of histamine from leukocytes in allergic patients than salbutamol. In fragments of human lung sensitized with allergic serum, the concentration required to inhibit histamine release by 50% was 2 x 10(-11) M for formoterol and 8.5 x 10(-9) M for salbutamol. The potency of salbutamol and formoterol in blocking specific 3H-dihydroalprenolol binding to beta-adrenoceptors on guinea pig lung membranes revealed that formoterol had higher affinity for beta-adrenoceptors than salbutamol, and the concentration required for half-maximum stimulation of adenylate cyclase was approximately 200-fold higher for salbutamol than for formoterol.
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PMID:Anti-allergic activity of formoterol, a new beta-adrenoceptor stimulant, and salbutamol in human leukocytes and human lung tissue. 619 99

The barrier function of cultured, macrovascular endothelial cells derived from bovine aorta was analyzed using confluent monolayers of cells and measuring the exchange of fluorescein dextrans of different molecular masses. The effects of beta-adrenoceptor agonists with different selectivity for beta 1- and beta 2-adrenoceptors (AR) were investigated. Formoterol, a novel high-affinity agonist for beta 2-AR recently introduced in the treatment of bronchial asthma, showed a significant reduction of cell permeability with subnanomolar concentrations, whereas the catecholamines (-)-isoproterenol and (-)-norepinephrine only showed significant effects with micromolar concentrations. In order to elucidate if this difference in potential to regulate cell permeability is related to appropriate changes in the selectivity and affinity of the agonists for beta 2 AR, we investigated the beta AR-coupled adenylate cyclase (AC) in membranes from endothelial cells and compared AC stimulation with the binding of agonists to the receptors using [125I](-)-iodopindolol as radioligand. beta-Adrenoceptors revealed to be closely coupled to AC as assessed by a similar magnitude of effects by receptor agonists in comparison to GTP analogues and direct stimulants of AC activity. AC activity was increased by formoterol in parallel to its receptor occupancy of beta 2AR with nanomolar concentrations which were 50-fold higher than those used for the regulation of cell permeability indicating the existence of spare receptors. In contrast to formoterol, the catecholamines (-)-isoproterenol and (-)-norepinephrine stimulated AC activity through both beta 1AR and beta 2AR. From the overproportional high contribution of beta 1AR to AC stimulation (42%) in comparison to its low fraction (13%) in receptor binding we calculated that beta 1AR is 3-4-fold more effectively coupled to AC than beta 2 AR.
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PMID:Regulation of endothelial permeability by beta-adrenoceptor agonists: contribution of beta 1- and beta 2-adrenoceptors. 810 57

1. The long-acting beta(2)-adrenoceptor agonist formoterol (10(-10)-10(-6) m) inhibited the IgE-dependent release of histamine from human lung mast cells in a concentration-dependent manner. Formoterol was more potent and a full agonist relative to the nonselective beta-adrenoceptor agonist isoprenaline. By contrast, the long-acting beta(2)-adrenoceptor agonist salmeterol (10(-10)-10(-6) m) was about two-thirds less efficacious than either formoterol or isoprenaline as an inhibitor of histamine release. 2. Isoprenaline, formoterol and salmeterol (all at 10(-5) m) increased total cell cAMP levels in mast cells over basal by 361+/-90 (P<0.05), 321+/-89 (P<0.05) and 64+/-24% (P>0.05), respectively. 3. Long-term (24 h) incubation of mast cells with formoterol (10(-6) m) or salmeterol (10(-6) m) essentially abolished the subsequent ability of isoprenaline to inhibit histamine release. Both formoterol and salmeterol were more effective at inducing the functional desensitisation than isoprenaline (10(-6) m) or the short-acting beta(2)-adrenoceptor agonist salbutamol (10(-6) m). 4. The desensitisation induced by long-term treatments with salmeterol and formoterol was specific for beta(2)-adrenoceptor-mediated inhibition of histamine release as the inhibitory effects of alternative cAMP-elevating compounds, prostaglandin E(2), a receptor-mediated activator of adenylate cyclase, and forskolin, a direct activator of adenylate cyclase, were unaffected by desensitising treatments. 5. Radioligand binding studies were performed to determine beta(2)-adrenoceptor density in cell membranes after pretreatment (24 h) of cells with agonists. Isoprenaline, formoterol and salmeterol (all at 10(-6) m) reduced beta(2)-adrenoceptor density by 13+/-5 (P>0.05), 49+/-13 (P<0.05) and 35+/-17% (P>0.05), respectively. 6. These data indicate that long-term exposure of mast cells to both salmeterol and formoterol can cause substantial levels of desensitisation to beta(2)-adrenoceptor-mediated responses in mast cells.
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PMID:Desensitisation of mast cell beta2-adrenoceptor-mediated responses by salmeterol and formoterol. 1466 24