Nociceptin/orphanin FQ and [Phe(1)psi(CH2-NH)Gly(2)]nociceptin(1-13)NH2 modulates the activity of hypothalamic paraventricular nucleus neurons in vitro

Nociceptin, also known as orphanin FQ (N/OFQ), an endogenous ligand for the orphan opioid receptor-like(1) (ORL1) receptor, is moderately expressed in the hypothalamic paraventricular nucleus (PVN) involved in the integrative control of the function of the endocrine and autonomic nervous systems. Ou r previous study demonstrated that intracerebroventricular administration o f N/OFQ elicits an inhibitor, action on the function of the cardiovascular and sympathetic nervous systems in conscious rats. However, the effects of N/OFQ on PVN neurons have not been examined. We investigated the effects of N/OFQ on PVN neurons using a whole-cell patch-clamp recording technique in rat brain slices. N/OFQ (30-1000 nM) hyperpolarized membrane potentials in type 1 and type 2 neurons of the PVN classified by the electrophysiologica l property. [Phe(1)psi (CH2-NH)Gly(2)]nociceptin(1-13)NH2 (Phe psi) (1-9 mu M), a presumed competitive antagonist of the ORL1 receptor, also hyperpolar ized membrane potential in both types of neurons. In voltage clamp studies, N/OFQ (3-3000 nM) activated a K+ current concentration-dependently in 69.7 % of PVN neurons with an EC50 of 72.4+/-12 nM. Phe psi (100-9000 nM) also a ctivated a K+ current with an EC,, of 818+/-162 nM in PVN neurons, and sign ificantly reduced the amplitude of the N/OFQ-stimulated current. The N/OFQ- induced current was not antagonized by the classical opioid receptor antago nist naloxone and putative antagonist nocistatin. These findings suggest th at N/OFQ may have a functional role in the PVN. (C) 2001 Elsevier Science B .V. All rights reserved.