TY - JOUR
T1 - Cell-autonomous regulation of mu-opioid receptor recycling by substance P
AU - Bowman, Shanna L.
AU - Soohoo, Amanda L.
AU - Shiwarski, Daniel J.
AU - Schulz, Stefan
AU - Pradhan, Amynah A.
AU - Puthenveedu, Manojkumar A.
N1 - Publisher Copyright:
© 2015 The Authors.
PY - 2015/3/24
Y1 - 2015/3/24
N2 - How neurons coordinate and reprogram multiple neurotransmitter signals is an area of broad interest. Here, we show that substance P (SP), a neuropeptideassociated with inflammatory pain, reprograms opioid receptor recycling and signaling. SP, through activation of the neurokinin 1 (NK1R) receptor, increases the post-endocytic recycling of the mu-opioid receptor (MOR) in trigeminal ganglion (TG) neurons in an agonist-selective manner. SP-mediated protein kinase C (PKC) activation is both required and sufficient for increasing recycling of exogenous and endogenous MOR in TG neurons. The target of this cross-regulation is MOR itself, given that mutation of either of two PKC phosphorylation sites on MOR abolishes the SP-induced increase inrecycling and resensitization. Furthermore, SP enhances the resensitization of fentanyl-induced, but not morphine-induced, antinociception in mice. Ourresults define a physiological pathway that cross-regulates opioid receptor recycling via direct modification of MOR and suggest a mode of homeostatic interaction between the pain and analgesic systems.
AB - How neurons coordinate and reprogram multiple neurotransmitter signals is an area of broad interest. Here, we show that substance P (SP), a neuropeptideassociated with inflammatory pain, reprograms opioid receptor recycling and signaling. SP, through activation of the neurokinin 1 (NK1R) receptor, increases the post-endocytic recycling of the mu-opioid receptor (MOR) in trigeminal ganglion (TG) neurons in an agonist-selective manner. SP-mediated protein kinase C (PKC) activation is both required and sufficient for increasing recycling of exogenous and endogenous MOR in TG neurons. The target of this cross-regulation is MOR itself, given that mutation of either of two PKC phosphorylation sites on MOR abolishes the SP-induced increase inrecycling and resensitization. Furthermore, SP enhances the resensitization of fentanyl-induced, but not morphine-induced, antinociception in mice. Ourresults define a physiological pathway that cross-regulates opioid receptor recycling via direct modification of MOR and suggest a mode of homeostatic interaction between the pain and analgesic systems.
UR - http://www.scopus.com/inward/record.url?scp=84925654067&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2015.02.045
DO - 10.1016/j.celrep.2015.02.045
M3 - Article
C2 - 25801029
AN - SCOPUS:84925654067
SN - 2639-1856
VL - 10
SP - 1925
EP - 1936
JO - Cell Reports
JF - Cell Reports
IS - 11
ER -