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Rat Frontal Cortex β 1 ‐Adrenoceptors Are Activated by the β 3 ‐Adrenoceptor Agonists SR 58611A and SR 58878A but Not by BRL 37344 or ICI 215,001
Author(s) -
Nisoli Enzo,
Tonello Cristina,
Benarese Marina,
Carruba Michele O.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65041580.x
Subject(s) - endocrinology , medicine , agonist , adenylyl cyclase , beta (programming language) , beta 3 adrenergic receptor , biology , antagonist , adrenergic receptor , cortex (anatomy) , receptor , chemistry , neuroscience , stimulation , computer science , programming language
Abstract: SR 58611A, a selective agonist of gut and brown adipose tissue β 3 ‐adrenoceptors (β 3 ARs), has been reported to have antidepressant‐like activity in rodents by indicating brain β 3 ARs as the sites of this property. SR 58611A and its acid metabolite SR 58878A, as opposed to BRL 37344, ICI 215,001, and CGP 12177, increased cyclic AMP levels in rat frontal cortex. ICI 215,001, differently from BRL 37344, at concentrations in the millimolar range antagonized norepinephrine‐ or (−)‐isoproterenol‐stimulated adenylyl cyclase partially. The increase of cyclic AMP levels induced by SR 58878A was blocked selectively by β 1 AR antagonist CGP 20712A but not by β 2 AR antagonist ICI 118,551. In addition, PCR analysis did not reveal β 3 AR mRNA, and no specific β 3 AR binding sites were detected by [ 3 H]CGP 12177 in rat frontal cortex. When down‐regulation of the β 1 AR ligand binding and mRNA levels had been induced in frontal cortex by chronic administration of imipramine, SR 58878A as well as norepinephrine and (−)‐isoproterenol increased the cyclic AMP production less markedly. Our findings indicate that β 3 ARs are absent in the adult rat frontal cortex, and that various β 3 AR agonists differently affect the frontal cortex β 1 ARs, indicating that SR 58611A may exert its putative antidepressant effect acting on the frontal cortex β 1 ARs.