Kappa opioid receptors internalization is protective against oxygen-glucose deprivation through β-arrestin activation and Akt-mediated signaling pathway

Butorphanol alleviates lipopolysaccharide‑induced inflammation and apoptosis of cardiomyocytes via activation of the κ‑opioid receptor

“…As a member of the G protein-coupled receptor superfamily, KOR is the product of a single gene, KOR1, in species including pigs and humans (32)(33)(34). KOR internalization has been reported to be induced by butorphanol, which is a crucial step in the receptor signaling transduction cascade, which can bring about pharmacological changes that are associated with the efficacy and side effects of opioids (35). Previous studies have reported that the opioid receptor comprises the MOR, δ-opioid receptor and KOR, and is not the product of a distinct gene; butorphanol shares a binding site with these three major opioid receptors, with an affinity ratio of 1:4:25, respectively (36,37).…”

A systematic review on the kappa opioid receptor and its ligands: New directions for the treatment of pain, anxiety, depression, and drug abuse

“…For example, salvinorin A was shown to activate the Akt signaling pathway, promote cell survival, and attenuate oxygenglucose deprivation (OGD)-induced cell injury, while a low concentration of RB-64 (where there was only G protein pathway activation without producing β-arrestin recruitment) did not. 95 These results suggested that KOR internalization through β-arrestin activation and Akt-mediated signaling pathway is a protective mechanism against OGD. 95 In a hot plate assay, administration of RB-64 to wild-type mice (3.0 mg/kg, s.c.) produced analgesia in as little as ten minutes, and the effects lasted for several hours.…”

“…95 These results suggested that KOR internalization through β-arrestin activation and Akt-mediated signaling pathway is a protective mechanism against OGD. 95 In a hot plate assay, administration of RB-64 to wild-type mice (3.0 mg/kg, s.c.) produced analgesia in as little as ten minutes, and the effects lasted for several hours. 62 As a G protein-biased KOR agonist, RB-64 was shown to have fewer side effects, such as motor incoordination and sedation, than the nonbiased KOR agonists U-69,593 and salvinorin A.…”

Salvinorin A for Stroke Rescue Purposes

“…Use of a KOR antagonist can abolish the protective effects and the brain vascular dilatation effects of SA [10,13]. Based on a recently published study using a cell culture hypoxia model, it appears that SA may be working through the beta-arrestin pathway rather than through the G protein pathway [22]. KORs are widely expressed throughout the brain.…”