1. Chronic β1-adrenoceptor blocker therapy induces hyperresponsiveness of the β2-adrenoceptor in human atrium. To investigate whether the β2-adrenoceptor sensitization induced by β1-adrenoceptor blockade is associated with altered gene expression of G-proteins, which couple the receptors to adenylate cyclase, we determined the mRNA expression of the α- and β-subunits of the stimulatory G-protein, Gs, and inhibitory G-protein, Gi, in human right atrial appendage by polymerase chain reaction and by enhanced chemiluminescence Northern blot analysis.

2. The polymerase chain reaction revealed bands of predicted size of Gsα, both short form and long form, all three Giα subtypes and three Gβ subtypes. In Northern blots, the digoxigenin-labelled antisense cRNA probe specific for Giα2 hybridized to a predominant band at 2.3 kb, whereas the Giα3 cRNA probe detected a message of 1.8 kb in total RNA extracted from human atrium. The cRNA probe encoding Gsα revealed one major band at 1.9 kb and one minor band at 1.7 kb. The Gβ cRNA probes detected messages of 3.4 kb for Gβ1, 1.8 kb for Gβ2 and 1.9 kb for Gβ3 in human atrium.

3. The mRNA levels of Gsα in β1-adrenoceptor-blocked atria (n = 12) were not significantly different from those in non-β-adrenoceptor-blocked atria (n = 12), nor were there any significant differences in the Giα2 mRNA levels between atria from patients treated with β1-adrenoceptor blockers and untreated patients. The ratios of 1.9-kb Gsα mRNA to 1.7-kb Gsα mRNA and of 1.9-kb Gsα mRNA to 2.3-kb Giα2 mRNA in β1-adrenoceptor-blocked patients were almost identical to those in non-β-adrenoceptor-blocked patients. Neither Gβ1 mRNA nor Gβ2 mRNA expression in β1-adrenoceptor-blocked atria differed significantly from that in non-β-adrenoceptor-blocked atria.

4. We conclude that the previously observed sensitization following β1-adrenoceptor-blockade of β2-adrenoceptors in human atria is unlikely to be mediated by altered gene expression of the α- and β-subunits of G-proteins.

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