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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effects of prenalterol on beta adrenergic responsiveness and receptors in the cerebral cortex of the rat.

The activity of the beta-adrenoceptor agonist, prenalterol, at beta adrenoceptors in the cerebral cortex of the rat and the effect of chronic intraperitoneal infusion of prenalterol on the biochemical responsiveness and density of cerebral cortical beta adrenoceptors was studied. Whereas isoproterenol caused a four-fold rise in the content of cyclic AMP in slices of cerebral cortex, prenalterol did not produce a significant increase in cyclic AMP. However, prenalterol inhibited the isoproterenol-stimulated increase in cyclic AMP in cortical slices in a concentration-dependent manner. Using an in vivo binding technique, prenalterol (3.8 mg/kg/hr) infused intraperitoneally through osmotic minipumps, penetrated the brain and significantly inhibited the binding of the beta adrenoceptor antagonist, [125I]iodopindolol (125I-IPIN), to cortical beta adrenoceptors. Infusion of prenalterol (3.8 mg/kg/hr) for 7 days resulted in a small (20%), but significant, reduction in the ability of isoproterenol to stimulate maximally the accumulation of cyclic AMP in slices of cerebral cortex. No alteration in the Bmax or KD of the binding of [125I]iodopindolol was observed in homogenates of cortex obtained from prenalterol-treated rats. Furthermore, no change was observed in the binding of the hydrophilic ligand [3H]CGP-12177 in homogenates of cortex. In this study, then, prenalterol exhibited properties in vitro of a beta adrenoceptor antagonist, but did cause modest desensitization of beta adrenoceptor responsiveness when administered continuously in vivo.[1]


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