| First Author | Bradaïa A | Year | 2005 |
| Journal | Proc Natl Acad Sci U S A | Volume | 102 |
| Issue | 8 | Pages | 3034-9 |
| PubMed ID | 15718284 | Mgi Jnum | J:96827 |
| Mgi Id | MGI:3531622 | Doi | 10.1073/pnas.0406632102 |
| Citation | Bradaia A, et al. (2005) beta-Arrestin2, interacting with phosphodiesterase 4, regulates synaptic release probability and presynaptic inhibition by opioids. Proc Natl Acad Sci U S A 102(8):3034-9 |
| abstractText | Most mu-opioid receptor agonists recruit beta-arrestin2, with some exceptions such as morphine. Surprisingly, however, the acute analgesic effect of morphine is enhanced in the absence of beta-arrestin2. To resolve this paradox, we examined the effects of morphine and fentanyl in acute brain slices of the locus coeruleus and the periaqueductal gray from beta-arrestin2 knockout mice. We report that, in these mice, presynaptic inhibition of evoked inhibitory postsynaptic currents was enhanced, whereas postsynaptic G protein-coupled K(+) (Kir3/GIRK) currents were unaffected. The frequency, but not amplitude, of miniature inhibitory postsynaptic currents was increased in beta-arrestin2 knockout mice, indicating a higher release probability compared to WT mice. The increased release probability resulted from increased cAMP levels because of impaired phosphodiesterase 4 function and conferred an enhanced efficacy of morphine to inhibit GABA release. Thus, beta-arrestin2 attenuates presynaptic inhibition by opioids independent of mu-opioid receptor-driven recruitment, which may make beta-arrestin2 a promising target for regulating analgesia. |
