title: β2- and β1-Adrenoceptor Expression Exhibits a Common Regulatory Pattern With GRK2 and GRK5 in Human and Animal Models of Cardiovascular Diseases.
abstract: To explore if genic expression of β(1)- or β(2)-adrenoceptors (ARs) exhibits a common regulatory pattern with G protein-coupled receptor kinase (GRK) 2, GRK3, or GRK5 expression, we determined messenger RNA levels for these genes in different tissues from human and animal models of cardiovascular disease. We measured genic expression by qRT polymerase chain reaction in the left and right ventricles or peripheral blood mononuclear cells from healthy (n = 21), hypertensive (n = 20), heart failure (n = 24), and heart transplanted patients (n = 17) or in left ventricle, peripheral blood mononuclear cells, and kidney from spontaneously hypertensive rats or L-N-methyl-arginine-induced hypertensive rats and their respective controls (n = 4-5). In diseased versus healthy subjects and rats, parallel changes in messenger RNA levels of GRK2 and β(2)-AR or GRK5 and β(1)-AR were observed in each territory. Therefore, without excluding other regulatory mechanisms, the parallelism observed suggests a common regulatory pattern for the β(1)-AR/GRK5 and β(2)-AR/GRK2 genes, which is independent of cellular type or pathology. This highlights the need to focus not only on GRKs but also on β(1)- or β(2)-AR changes to completely understand the involvement of β-AR/GRK pathways in cardiovascular diseases.
authors.affiliation: *Departamento de Farmacología, Facultad de Farmacia, Universitat de València, Valencia, Spain; †Servicio de Cardiología, Hospital La Fe, Valencia, Spain; and ‡Hospital de la Ribera, Alzira, Spain.
authors.forename: Fermí
authors.initials: F
authors.lastname: Montó
authors.forename: Eduardo
authors.initials: E
authors.lastname: Oliver
authors.forename: Diana
authors.initials: D
authors.lastname: Vicente
authors.forename: Francisco
authors.initials: F
authors.lastname: Buendía
authors.forename: Joaquín
authors.initials: J
authors.lastname: Rueda
authors.forename: Jaime
authors.initials: J
authors.lastname: Agüero
authors.forename: Luis
authors.initials: L
authors.lastname: Almenar
authors.forename: Carmen
authors.initials: C
authors.lastname: Valldecabres
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rovira
authors.forename: Vicente
authors.initials: V
authors.lastname: Muedra
authors.forename: María A
authors.initials: MA
authors.lastname: Noguera
authors.forename: María D
authors.initials: MD
authors.lastname: Ivorra
authors.forename: Pilar
authors.initials: P
authors.lastname: DʼOcon
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D004195:Disease Models, Animal; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000378:metabolism*; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006331:Heart Diseases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C547787:ADRB1 protein, human; C553443:ADRB2 protein, human; C547789:Adrb1 protein, rat; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; C496567:GRK2 protein, human; C496569:Grk2 protein, rat; D054769:G-Protein-Coupled Receptor Kinase 2; D054774:G-Protein-Coupled Receptor Kinase 5; C517898:GRK5 protein, human; C517897:Grk5 protein, rat; D019331:NG-Nitroarginine Methyl Ester