It has been suggested that there is a preferential coupling in heart muscle between the inhibitory G protein (G i ) and the β 2 -subtype of the β-adrenergic receptor (β-AR), since pertussis toxin (which inactivates G i ) reveals latent β 2 -ARs in rat and mouse myocytes. We have previously shown that guinea pigs treated with norepinephrine (NE) for 7 days have myocytes that are desensitized to β-AR-agonist stimulation, and that pertussis toxin restores these responses. The purpose of the present investigation was to determine whether pertussis toxin specifically upregulated β 2 -ARs in myocytes from NE-treated guinea pigs. The sole β-AR subtype in control guinea pig myocytes was confirmed as β 1 -AR by radioligand binding, single-cell autoradiography, and concentration-response curves to isoproterenol in contracting myocytes. In contrast, a minor pool of β 2 -ARs was observed in rat myocytes by use of the same methods. NE treatment decreased the maximum isoproterenol response (relative to high Ca 2+ ) from 0.89 ± 0.06 to 0.58 ± 0.08 ( n = 7, P < 0.01) and the pD 2 (−log EC 50 ) from 8.8 ± 0.2 to 7.5 ± 0.2 ( n = 7, P < 0.01). Pertussis toxin treatment increased the isoproterenol-to-Ca 2+ ratio to 0.88 ± 0.04 ( n = 6, P < 0.05) and the pD 2 to 8.6 ± 0.3 ( P < 0.01). This was not mediated by increases in either number or function of β 2 -ARs. G i is therefore able to modulate β 1 -AR responses in guinea pig myocytes.
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