Nociceptin inhibits T-type Ca2+ channel current in rat sensory neurons by a G-protein-independent mechanism

Abstract

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 g(ca)) in much the same way as μ-, δ-, and κ-opioids. We report an action of nociceptin that is not shared by morphine: the suppression of low- voltage-activated, transient calcium (barium) current (I(Ba,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-γ-S (100 μM), GDP-β-S (2 mM), or aluminum fluoride (AlF3) (100 μM) in the patch pipette failed to provide evidence for G-protein involvement in nociceptin-induced I(Ba,T) suppression. By contrast, both morphine and nociceptin suppressed HVA g(Ca), and the latter response was affected by intracellular GTPγ-S, GDP- β-S, and AlF3 in ways that confirmed G-protein involvement. The selective effect of nociceptin on I(Ba,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.