RGD Reference Report - Beta1-adrenoceptors in rat anterior pituitary may be constitutively active. Inverse agonism of CGP 20712A on basal 3',5'-cyclic adenosine 5'-monophosphate levels. - Rat Genome Database

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Beta1-adrenoceptors in rat anterior pituitary may be constitutively active. Inverse agonism of CGP 20712A on basal 3',5'-cyclic adenosine 5'-monophosphate levels.

Authors: Janssens, K  Boussemaere, M  Wagner, S  Kopka, K  Denef, C 
Citation: Janssens K, etal., Endocrinology. 2008 May;149(5):2391-402. Epub 2008 Jan 17.
RGD ID: 5129138
Pubmed: PMID:18202135   (View Abstract at PubMed)
DOI: DOI:10.1210/en.2007-1397   (Journal Full-text)

Catecholamines directly stimulate GH, ACTH, and prolactin secretion from rat anterior pituitary through the beta(2)-adrenoceptor (AR). We recently showed that gonadotrophs express the beta(1)-AR and that glucocorticoids drastically increase its mRNA expression level. The present investigation explores whether beta(1)-ARs are functionally coupled to adenylate cyclase. In anterior pituitary cell aggregates, the highly selective beta(1)-AR antagonists CGP 20712A and ICI 89,406-8a attenuated isoproterenol-stimulated cAMP accumulation, but no agonist action of norepinephrine could be detected. Remarkably, CGP 20712A inhibited basal cAMP levels by its own for at least 50%, an action that tended to be more effective in dexamethasone-supplemented medium. The latter effect was abolished by the beta-AR antagonist carvedilol, but not by other beta-AR antagonists. Pretreatment with pertussis toxin abolished the action of CGP 20712A on basal cAMP. CGP 20712A also attenuated isoproterenol-induced cAMP accumulation in the gonadotroph cell lines alphaT3-1 and LbetaT2, but not in the somatotroph precursor cell line GHFT and the folliculo-stellate cell line TtT/GF. However, in LbetaT2 cells CGP 20712A did not inhibit basal cAMP levels by its own. The present data suggest that beta(1)-AR in the anterior pituitary is positively coupled to adenylyl cyclase but is constitutively active in a pertussis toxin-sensitive manner. CGP 20712A may act as an inverse agonist with approximately 50% negative intrinsic activity, suggesting that the beta(1)-AR significantly contributes to basal adenylate cyclase activity in the pituitary.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Adrb1Ratpositive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Adrb1  (adrenoceptor beta 1)


Additional Information