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).