A Caged Enkephalin Optimized for Simultaneously Probing Mu and Delta Opioid Receptors.
Authors | |
Abstract | Physiological responses to the opioid neuropeptide enkephalin often involve both mu and delta opioid receptors. To facilitate quantitative studies into opioid signaling, we previously developed a caged [Leu]-enkephalin that responds to ultraviolet irradiation, but its residual activity at delta receptors confounds experiments that involve both receptors. To reduce residual activity, we evaluated side-chain, N-terminus, and backbone caging sites and further incorporated the dimethoxy-nitrobenzyl moiety to improve sensitivity to ultraviolet light-emitting diodes (LEDs). Residual activity was characterized using an in vitro functional assay, and the power dependence and kinetics of the uncaging response to 355 nm laser irradiation were assayed using electrophysiological recordings of mu opioid receptor-mediated potassium currents in brain slices of rat locus coeruleus. These experiments identified N-MNVOC-LE as an optimal compound. Using ultraviolet LED illumination to photoactivate N-MNVOC-LE in the CA1 region of hippocampus, we found that enkephalin engages both mu and delta opioid receptors to suppress inhibitory synaptic transmission. |
Year of Publication | 2018
|
Journal | ACS Chem Neurosci
|
Volume | 9
|
Issue | 4
|
Pages | 684-690
|
Date Published | 2018 04 18
|
ISSN | 1948-7193
|
DOI | 10.1021/acschemneuro.7b00485
|
PubMed ID | 29266926
|
PubMed Central ID | PMC5906201
|
Links | |
Grant list | R01 MH085498 / MH / NIMH NIH HHS / United States
R00 DA034648 / DA / NIDA NIH HHS / United States
R01 MH100568 / MH / NIMH NIH HHS / United States
T32 GM007240 / GM / NIGMS NIH HHS / United States
K99 DA034648 / DA / NIDA NIH HHS / United States
|