Autor: |
Roca R; Occupational Observatory, Miguel Hernández University (UMH) of Elche, 03202 Elche, Spain., Esteban P; Occupational Observatory, Miguel Hernández University (UMH) of Elche, 03202 Elche, Spain., Zapater P; CIBERehd, Carlos III Health Institute, 28029 Madrid, Spain., Inda MD; Neuropharmacology on Pain (NED) Research Group, ISABIAL‑FISABIO, General Hospital of Alicante, 03010 Alicante, Spain., Conte AL; Occupational Observatory, Miguel Hernández University (UMH) of Elche, 03202 Elche, Spain., Gómez-Escolar L; Liver Unit, General Hospital of Alicante, 03010 Alicante, Spain., Martínez H; Clinical R&D Area, Bioiberica S.A., 08029 Barcelona, Spain., Horga JF; Clinical Pharmacology, General Hospital of Alicante, 03010 Alicante, Spain., Palazon JM; Liver Unit, General Hospital of Alicante, 03010 Alicante, Spain., Peiró AM; Clinical Pharmacology, General Hospital of Alicante, 03010 Alicante, Spain. |
Abstrakt: |
The present study was designed to investigate the functional status of β2 adrenoceptors (β2AR) in two models of chronic inflammatory disease: liver cirrhosis (LC) and osteoarthritis (OA). The β2AR gene contains three single nucleotide polymorphisms at amino acid positions 16, 27 and 164. The aim of the present study was to investigate the potential influence of lymphocyte β2AR receptor functionality and genotype in LC and OA patients. Blood samples from cirrhotic patients (n=52, hepatic venous pressure gradient 13±4 mmHg, CHILD 7±2 and MELD 11±4 scores), OA patients (n=30, 84% Kellgren‑Lawrence severity 4 grade, 14% knee replacement joint) and healthy volunteers as control group (n=26) were analyzed. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood and basal and isoproterenol induced adenylate cyclase activity (isoproterenol stimulus from 10‑9 to 10‑4 mM), and β2AR allelic variants (rs1042713, rs1042714, rs1800888) were determined. β2AR functionality was decreased in the two different models of chronic inflammatory disease studied, OA (50% vs. control) and LC (85% vs. control). In these patients, the strength of the β2AR response to adrenergic stimulation was very limited. Adrenergic modulation of PBMC function through the β2AR stimulus is decreased in chronic inflammatory processes including LC and OA, suggesting that the adrenergic system may be important in the development of these processes. |