Activation of an inwardly rectifying K+ conductance by orphanin-FQ/nociceptin in vasopressin-containing neurons.
Activation of an inwardly rectifying K+ conductance by orphanin-FQ/nociceptin in vasopressin-containing neurons.
复制标题
孤啡肽-FQ/伤害感受肽在含加压素的神经元中激活内向整流 K 电导。
DOI：
10.1159/000054441
复制
发表时间：
1999
影响因子：
4.1
通讯作者：
Kelly,MJ
中科院分区：
文献类型：
--
作者：
Slugg,RM;Rønnekleiv,OK;Grandy,DK;Kelly,MJ
The orphanin-FQ/nociceptin (OFQ/N) receptor (previously, ORL 1, LC132) has been shown to be coupled to an inwardly rectifying K+ conductance in several neuronal populations. Although OFQ/N receptor mRNA is densely expressed in the supraoptic nucleus (SON), little is known about its coupling to effector system (s). The present study examined the effects of OFQ/N on guinea pig magnocellular neurons within the SON using intracellular recording from hypothalamic slices. In the presence of tetrodotoxin, OFQ/N hyperpolarized 48 of 48 SON magnocellular neurons, 24 of which were subsequently identified by immunocytochemistry as arginine vasopressin positive (AVP+). Nineteen of the 48 SON neurons, including 7 which were AVP+, responded to OFQ/N with an outward current that reversed at the K+ equilibrium potential (E K+) and a decrease in slope resistance consistent with the activation of an inwardly rectifying K+ channel. In 4 of these neurons, BaCl 2 significantly attenuated both the hyperpolarization and the decrease in slope resistance induced by OFQ/N. Twenty-one SON neurons, 13 of which were AVP+, responded to OFQ/N with an increase in slope resistance which did not reverse at E K+. An additional 5 neurons (2 were AVP+) were treated with the gap junction blocking agent carbenoxolone (CARB). CARB induced a small hyperpolarization, increased slope resistance and significantly reduced the subsequent OFQ/N-induced hyperpolarization. However, when the CARB and CARB plus OFQ/N hyperpolarizations were summed in these 5 cells, they were no different than the OFQ/N hyperpolarization alone. The effect of two putative OFQ/N receptor antagonists was also evaluated. The ĸ 3-opioid antagonist naloxone benzoylhydrazone was without effect (n= 3), and the 13-amino-acid [Phe 1 Ψ (CH 2-NH) Gly 2] OFQ/N (1–13) NH 2 OFQ/N analog produced a small hyperpolarization on its own in addition to partially antagonizing the effects of OFQ/N (n= 3). Taken together, these results suggest that OFQ/N acts upon SON neurons through two mechanisms, one which hyperpolarizes the neuron by activating an inwardly rectifying K+ conductance, and another which may increase membrane resistance by closing the low-resistance gap junctions.
