Fig. 7: The TM3_MOR-TAT peptide rescued MOR activity by disrupting the MOR–CCKBR interaction and remitted CCK-8-induced antagonism to morphine analgesia.

a A representative result of ERK1/2 phosphorylation immunoblot assay. The top panel showed phosphorylated ERK1/2 bands, and the bottom panel showed total ERK1/2 bands. b Statistical results. The gray density values of the bands were obtained by Quantity One software and analyzed with GraphPad Prism 5.0 after gray density values normalized. Compared with the scrambled-TAT treatment, the TM3_MOR-TAT treatment significantly increased the phosphorylation of ERK1/2. *p < 0.05, t-test, n = 3. Data are expressed as the mean ± SEM. c TM3_MOR-TAT pretreatment enhanced DAMGO-induced inhibition of cAMP accumulation. d TM3_MOR-TAT reversed CCK-8 antagonism to morphine analgesia. Percent of maximum possible effect (%MPE) 30 min after morphine (2 mg/kg, s.c.) application. Compared with saline group, CCK-8 (i.t.) pretreatment decreased the analgesic effects of morphine. However, pretreatment with TM3_MOR-TAT 4 h before CCK-8 and morphine injection showed significantly stronger analgesic effects compared to that with scrambled-TAT pretreatment. *p < 0.05, t-test. Data are represented as the mean ± SEM