3. Results
3.1. Effects of GRK2 inhibitors on the respiratory depressive
effects of morphine andfentanyl
A GRK2 inhibitor was applied to the upper ventricles of normal animals
to inhibit downstream β-arrestin2 signaling. The effect of the
β-arrestin2 signaling pathway on respiratory depression induced by
morphine and fentanyl was then examined in normal mice.
The timing of respiratory depression induced by fentanyl and morphine
was different. Respiratory depression induced by fentanyl occurred
rapidly and peaked 5 min after administration, whereas that induced by
morphine peaked 30 min after administration. In the experiment examining
the effects of GRK2 inhibitors on morphine-induced respiratory
depression (Fig 1), there were no statistical differences in the
respiratory rate, inspiratory time, expiratory time, and minute
ventilation between the groups before administration. After
administration, animals given 50 mg/kg morphine subcutaneously had
significantly lower respiratory rates than those administered control
solvent + normal saline, but inhibitors did not affect the respiratory
depressant effects of morphine (Fig. 1a). Similarly, significant changes
in the inspiratory time and expiratory time were observed in comparison
to the control group, and the increases were larger in the inhibitor +
morphine group than in the solvent + morphine group (Fig. 1b, c). There
was no statistically significant change in tidal volume between the two
groups (Fig. 1d). In the experiment on the effect of a GRK2 inhibitor on
fentanyl-induced respiratory depression, there was no statistical
difference in the respiratory rate, inspiratory time, expiratory time,
and minute ventilation between the groups before and after the
experiment (Fig. 2).