The peptide orphanin FQ inhibits beta-endorphin neurons and neurosecretory cells in the hypothalamic arcuate nucleus by activating an inwardly-rectifying K+ conductance.
The peptide orphanin FQ inhibits beta-endorphin neurons and neurosecretory cells in the hypothalamic arcuate nucleus by activating an inwardly-rectifying K+ conductance.
复制标题
肽孤啡肽 FQ 通过激活内向整流 K 电导来抑制下丘脑弓状核中的 β-内啡肽神经元和神经分泌细胞。
DOI：
10.1159/000054301
复制
发表时间：
1998
影响因子：
4.1
通讯作者：
Kelly,MJ
中科院分区：
文献类型：
--
作者：
Wagner,EJ;Rønnekleiv,OK;Grandy,DK;Kelly,MJ
Orphanin FQ (OFQ) is a novel heptadecapeptide whose structure resembles that of dynorphin A 1–17. Its receptor shares appreciable homology with µ-, δ-and ĸ-opioid receptors, and is highly expressed in the hypothalamus. The present study examined the effects of OFQ on neurons within the arcuate nucleus (ARC) of the mediobasal hypothalamus, using intracellular recordings from coronal slices. In current clamp, OFQ produced a hyperpolarization of ARC neurons, including those immunopositive for β-endorphin, tyrosine hydroxylase and gonadotropin-releasing hormone. This hyperpolarization was dose-dependent, insensitive to antagonism by naloxone and was associated with a decrease in input resistance. In voltage clamp, OFQ produced an outward current associated with an increase in conductance. Varying the extracellular K+ concentration shifted the reversal potential for the OFQ response to the degree predicted by the Nernst equation. Furthermore, barium chloride markedly attenuated both the OFQ-induced hyperpolarization and decrease in input resistance. Administration of maximally effective concentrations of OFQ, followed by coadministration of maximal concentrations of either OFQ and the µ-opioid receptor agonist DAMGO or OFQ and the GABA B receptor agonist baclofen produced additive hyperpolarizations and outward currents. If DAMGO was applied first, followed by the coadministration of DAMGO and OFQ, then the responses were occluded. Taken together, these results indicate that OFQ inhibits β-endorphin neurons, as well as A 12 dopamine and GnRH neurosecretory cells, within the ARC by activating a subset of inwardly-rectifying K+ channels. This suggests that OFQ is not only an antiopioid peptide, but that it also modulates the hypothalamo-pituitary axis and, ultimately, reproductive behavior.
