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 effects of methylprednisolone (Solu-Medrol, CAS 83-43-2) on isoprenaline (isoproterenol)-induced decreases in the number of beta-receptors and adenylate cyclase activities in rat hearts. Rats were divided into 4 groups: 1. the control group, untreated; 2. the ISPOd group; 3. the ISP7d group, 10 mg/kg of isoprenaline was subsequently injected once a day for 6 successive days, and rats were cervically dislocated 15 h or 7 days after the last isoprenaline injection, respectively; 4. the ISP + MP7d group, 20 mg/kg of methylprednisolone was intraperitoneally injected once a day for 7 successive days following 6 successive days of isoprenaline injection, and rats were cervically dislocated. A significant decrease in the number of beta-receptors was observed (28.9 +/- 4.2 fmol/mg protein) after 6 successive isoprenaline injections compared with the control (41.7 +/- 3.6), and this significant decrease persisted for 7 days (32.6 +/- 5.8). Administration of methylprednisolone accelerated the recovery of beta-receptors (38.4 +/- 5.1) 7 days after the last isoprenaline injection. Adenylate cyclase activities were also decreased by successive isoprenaline treatments (isoprenaline-stimulated adenylate cyclase activity, 13.9 +/- 2.7 pmol/min/mg protein; basal adenylate cyclase activity, 11.2 +/- 1.7) compared with the control (isoprenaline-stimulated, 25.7 +/- 3.7; basal, 18.1 +/- 2.4). Significant decreases in adenylate cyclase activities were observed 7 days after isoprenaline administration (isoprenaline-stimulated, 17.7 +/- 3.9; basal, 14.8 +/- 2.4). Methylprednisolone also accelerated the recoveries (isoprenaline-stimulated, 20.3 +/- 2.9; basal, 17.1 +/- 3.9). These results indicate that methylprednisolone accelerated the recovery of the decrease in beta-adrenergic responsiveness caused by successive administrations of isoprenaline.
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PMID:Effect of methylprednisolone on recovery of beta-adrenergic desensitization in rat hearts. 165 Feb 27

1. The time course of recovery of reduced beta-adrenoceptors caused by ovalbumin (OA) challenge was investigated using guinea-pigs. 2. The effects of prednisolone on the recovery time course were also evaluated. 3. beta- and alpha 1-receptor assays were performed using lung membranes. Adenylate cyclase activity was also measured. 4. OA challenge reduced the number of beta-adrenoceptors by 35%, and a significant decrease (13%) persisted for 7 days. The number of beta-adrenoceptor recovered after 14 days. 5. OA challenge elevated the number of alpha 1-adrenoceptors. A significant increase (24%) was observed after 7 days, and it took a further 7 days for the recovery. 6. After OA challenge there was a significant decrease in adenylate cyclase activity after 7 days, which recovered after a further 7 days. 7. Inhalation of prednisolone accelerated the recovery of beta-adrenergic responsiveness, though it did not affect the recovery of the number of alpha 1-adrenoceptors. Prednisolone inhalation also elevated beta-adrenergic responsiveness in non-asthmatic subjects. 8. It is concluded that reduced beta-adrenergic responsiveness caused by OA challenge persisted for 7 days and recovered after a further 7 days. Steroid hormone increased beta-adrenoceptors.
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PMID:Time course of recovery of beta- and alpha 1-adrenoceptors in experimental asthma. 216 62

The receptor alterations involved in catecholamine-induced desensitization of adenylate cyclase in human neutrophils have been investigated as has the ability of hydrocortisone to modify such alterations. Incubation of human neutrophils with isoproterenol for 3 h in vitro resulted in an 86% reduction in the ability of isoproterenol to stimulate cyclic AMP accumulation in the cells. Two types of receptor alterations were documented. There was a 40% reduction in the number of beta adrenergic receptors (42 vs. 25 fmol/mg protein, P < 0.005) present after desensitization as assessed by [(3)H]dihydroalprenolol ([(3)H]DHA) binding. In addition the receptors appeared to be relatively uncoupled from adenylate cyclase. This uncoupling was assessed by examining the ability of the agonist isoproterenol to stabilize a high-affinity form of the receptor, detected by computer modelling of competition curves for [(3)H]DHA binding. Desensitized receptors were characterized by rightward-shifted agonist competition curves. When hydrocortisone was added to the desensitizing incubations (combined treatment) there was a statistically significant attenuation in the desensitization process as assessed by the ability of isoproterenol to increase cyclic AMP levels in the cells. Although combined treatment did not prevent the decline in receptor number, it did attenuate the uncoupling of the receptors. Combined treatment resulted in competition curves intermediate between the control and the rightward-shifted desensitization curves. Prednisolone was similar to hydrocortisone in attenuating isoproterenol-induced uncoupling. Thus, steroids appeared to attenuate agonist-induced desensitization of the beta adrenergic receptor-adenylate cyclase system by dampening the ability of agonists to uncouple receptors without modifying their ability to promote down-regulation of beta adrenergic receptors.
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PMID:In vitro desensitization of beta adrenergic receptors in human neutrophils. Attenuation by corticosteroids. 629 79