title: Heart adrenoceptor gene expression and binding sites in the human failing heart.
abstract: Adrenergic regulation of the heart function is well documented by many studies. Catecholamines act through alpha(1)-, beta(1)-, beta(2)-, and beta(3)-adrenoceptors (ARs) in the heart. There are many findings about the changes of beta(1)- and beta(2)-AR in heart failure (HF). On the other hand, the role of other AR subtypes is not clear yet. We focused on determining how HF could affect gene expression and specific ligand binding to alpha(1A)-, alpha(1B)-, alpha(1D)-, beta(1)-, beta(2)-, and beta(3)-AR. Hearts from 11 patients with HF subjected to transplantation were investigated. As a control, corresponding parts from hearts not suitable for transplantation were used. We have found significantly higher mRNA levels of alpha(1A)-, alpha(1B)-,beta(1)-, and beta(2)-AR in the left ventricle of failing hearts compared to the levels in controls. beta(3)-AR mRNA levels in the left ventricle of failing hearts were not changed. No changes in mRNA levels of all receptors studied in other cardiac areas were found. On the other hand, binding studies showed a substantial decrease in left ventricles of failing hearts in all alpha(1)-AR subtypes and in beta(1)- and beta(2)-AR. However, the binding to beta(3)-AR was not changed. Our results suggest that alpha(1)-AR changes might be part of a compensatory mechanism, by which the heart suffering from the HF tries to secure its function, and it could be hypothesized that ineffective beta(3)-AR regulation might be involved in development of HF. According to our knowledge, this is the first report about the beta(3)-AR binding in HF.
authors.affiliation: The National Institute of Cardiovascular Diseases, Bratislava, Slovakia.
authors.forename: Viliam
authors.initials: V
authors.lastname: Fischer
authors.forename: Ivan
authors.initials: I
authors.lastname: Gabauer
authors.forename: Andrej
authors.initials: A
authors.lastname: Tillinger
authors.forename: Martina
authors.initials: M
authors.lastname: Novakova
authors.forename: Ivan
authors.initials: I
authors.lastname: Pechan
authors.forename: Olga
authors.initials: O
authors.lastname: Krizanova
authors.forename: Richard
authors.initials: R
authors.lastname: Kvetnanský
authors.forename: Jaromir
authors.initials: J
authors.lastname: Myslivecek
mesh_terms: D000818:Animals; D001665:Binding Sites; D005260:Female; D015870:Gene Expression; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology* / Q000503:physiopathology*; D006333:Heart Failure / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D008297:Male; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D011941:Receptors, Adrenergic / Q000235:genetics / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D011941:Receptors, Adrenergic