title: Functional status of beta-2-adrenoceptor in isolated membranes of mature erythrocytes from patients with cirrhosis and oesophageal varices.
abstract: Propranolol is a widely used drug for prophylaxis of variceal bleeding in patients with cirrhosis, but not all patients show an adequate clinical response. This variability may be in relation to beta adrenoceptor activity, but no information is available in this setting. Thirty-nine patients with advanced cirrhosis and presence of oesophageal varices were sequentially included. We studied the function of beta-2-adrenoceptor in isolated membranes of mature erythrocytes obtained from patients by measuring cyclic AMP (cAMP) production before and after isoproterenol. Blood samples obtained from 11 healthy volunteers were used as control. Patients showed a six-fold increase in the mean basal cAMP production as compared to healthy volunteers. Isoproterenol produced a small, non-significantly and highly variable increase in the AC activity in patients compared with controls. cAMP values remain stable after three months of continuous treatment with oral beta-blockers in both groups. Patients without antecedent of variceal bleeding or with an active alcohol intake showed a significantly higher isoproterenol effect. In conclusion, beta-receptor function in human erythrocytes membranes is altered in patients with cirrhosis and oesophageal varices.
authors.affiliation: Clinical Pharmacology Unit, Hospital General Universitario, and Departamento de Farmacología and Terapéutica, Facultad de Medicina, Universidad Miguel Hernández, San Juan de Alicante, Spain.
authors.forename: F T
authors.initials: FT
authors.lastname: Hernández
authors.forename: P
authors.initials: P
authors.lastname: Zapater
authors.forename: E
authors.initials: E
authors.lastname: De-Madaria
authors.forename: J M
authors.initials: JM
authors.lastname: Palazón
authors.forename: S
authors.initials: S
authors.lastname: Pascual
authors.forename: J
authors.initials: J
authors.lastname: Irurzun
authors.forename: J
authors.initials: J
authors.lastname: Such
authors.forename: M
authors.initials: M
authors.lastname: Perez-Mateo
authors.forename: J F
authors.initials: JF
authors.lastname: Horga
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000428:Alcohol Drinking / Q000009:adverse effects; D000242:Cyclic AMP / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology*; D004932:Esophageal and Gastric Varices / Q000097:blood / Q000378:metabolism* / Q000517:prevention & control; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018343:Receptors, Adrenergic, beta-2; D011433:Propranolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol