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Volume 17, Number 22,
Issue of November 15, 1997
pp. 8721-8728
Nociceptin Inhibits T-Type Ca2+ Channel Current in
Rat Sensory Neurons by a G-Protein-Independent Mechanism
Received July 14, 1997; revised Sept. 2, 1997; accepted Sept. 3, 1997.
Fuad A. Abdulla and
Peter A. Smith
Department of Pharmacology, University of Alberta, Edmonton,
Alberta, Canada, T6G 2H7
Nociceptin (orphanin FQ) is a novel, opioid-like, heptadecapeptide
that is an endogenous ligand for the opioid receptor-like (ORL1) receptor. Unlike classical opioids,
nociceptin can produce hyperalgesia when injected
intracerebroventricularly into mice. Despite this, nociceptin has been
reported to decrease transmitter release, activate an inwardly
rectifying K+ conductance, and suppress
high-voltage-activated Ca2+ channel conductances
(HVA gCa) in much the same way as
µ-,  -, and  -opioids. We report an action of nociceptin that is
not shared by morphine: the suppression of low-voltage-activated,
transient calcium (barium) current
(IBa,T) in acutely dissociated rat
dorsal root ganglion (DRG) neurons (EC50 = 100 nM). This effect was reflected as inhibition of bursts of
action potentials that can be evoked in "medium-sized" DRG neurons.
Experiments with GTP- -S (100 µM), GDP- -S (2 mM), or aluminum fluoride (AlF3) (100 µM) in the patch pipette failed to provide evidence for
G-protein involvement in nociceptin-induced
IBa,T suppression. By contrast, both
morphine and nociceptin suppressed HVA
gCa, and the latter response was affected by intracellular GTP--S, GDP--S, and AlF3 in
ways that confirmed G-protein involvement. The selective effect of
nociceptin on IBa,T may therefore be
relevant to understanding why its behavioral actions differ from those
of other opioids. This G-protein-independent effect of the action of
nociceptin may reflect a new general mechanism of action for opioid
peptides within the nervous system.
Key words:
LC132 receptor;
neuropathic pain;
sympathetic ganglion;
orphan receptor;
enkephalin;
endorphin;
spinal cord;
afterdepolarization;
anticonvulsant
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