Nociceptin Inhibits T-Type Ca2+Channel Current in Rat Sensory Neurons by a G-Protein-Independent Mechanism

Open Access
Publisher Website
Google Scholar
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 (HVAgCa) 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 (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-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-inducedIBa,Tsuppression. By contrast, both morphine and nociceptin suppressed HVAgCa, and the latter response was affected by intracellular GTP-γ-S, GDP-β-S, and AlF3in ways that confirmed G-protein involvement. The selective effect of nociceptin onIBa,Tmay 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.