Rm. Slugg et al., Activation of an inwardly rectifying K+ conductance by orphanin-FQ/nociceptin in vasopressin-containing neurons, NEUROENDOCR, 69(5), 1999, pp. 385-396
The orphanin-FQ/nociceptin (OFQ/N) receptor (previously, ORL1, LC132) has b
een 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 effect
or system(s). The present study examined the effects of OFQ/N on guinea pig
magnocellular neurons within the SON using intracellular recording from hy
pothalamic 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 wi
th an outward current that reversed at the K+ equilibrium potential (EK+) a
nd a decrease in slope resistance consistent with the activation of an inwa
rdly rectifying K+ channel. In 4 of these neurons, BaCl2 significantly atte
nuated both the hyperpolarization and the decrease in slope resistance indu
ced 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 EK+. A
n additional 5 neurons (2 were AVP(+)) were treated with the gap junction b
locking agent carbenoxolone (CARB). CARE induced a small hyperpolarization,
increased slope resistance and significantly reduced the subsequent OFQ/N-
induced hyperpolarization. However, when the CARE and CARE plus OFQ/N hyper
polarizations were summed in these 5 cells, they were no different than the
OFQ/N hyperpolarization alone. The effect of two putative OFQ/N receptor a
ntagonists was also evaluated. The kappa(3)-opioid antagonist naloxone benz
oylhydrazone was without effect (n = 3), and the 13-amino-acid [Phe(1)Psi(C
H2-NH)Gly(2)]OFQ/N(1-13)NH2 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
th rough two mechanisms, one which hyperpolarizes the neuron by activating
an inwardly rectifying K+ conductance, and another which may increase memb
rane resistance by closing the low-resistance gap junctions.