Pharmacological profile of constitutively active NOP opioid receptors heterologously expressed in rat stellate ganglion neurons

Abstract

We have previously shown that opioid receptor‐like 1 (NOP) receptors are expressed in rat stellate ganglion (SG) neurons and that activation of the receptors with nociceptin/orphanin FQ (N/OFQ) results in voltage‐dependent (VD) inhibition of N‐type Ca2+ channel currents. In the present study, we examined the effect of NOP receptor overexpression in SG neurons on the pharmacological response to five high affinity NOP receptor blockers on Ca2+ channel currents employing the whole‐cell patch‐clamp technique. In control neurons, 0.1 μM N/OFQ inhibited Ca2+ currents 41.0 ± 3.6% (n=29). On the other hand, all five NOP receptor antagonists (1 μM) significantly (P < 0.01) blocked the N/OFQ‐mediated Ca2+ current inhibition, being per se inactive. In neurons overexpressing NOP receptors, application of UFP‐101 resulted in Ca2+ channel inhibition of 39.9 ± 2.4% (n=5). On the other hand, exposure of cells to Compound 24, JTC‐801 and TRAP‐101 enhanced the Ca2+ current amplitude by 60.8 ± 8.7 (n=6), 51.0 ± 13.9 (n=5) and 59.9 ± 6.8% (n=5), respectively. Finally, application of (±)J‐113397 resulted in a small increase in Ca2+ current amplitude of 11 ± 5.1% (n=6). The data suggest that the effect of NOP receptor blockers is modulated when the receptors are constitutively active such that partial, neutral or inverse agonistic effects can be observed.