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Actions of nociceptin/orphanin FQ and other prepronociceptin products on rat rostral ventromedial medulla neurons in vitro
Author(s) -
Vaughan Christopher W.,
Connor Mark,
Jennings Ernest A.,
Marinelli Silvia,
Allen Richard G.,
Christie MacDonald J.
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.00849.x
Subject(s) - rostral ventromedial medulla , nociceptin receptor , in vitro , neuroscience , chemistry , rostral ventrolateral medulla , medulla oblongata , medulla , nociception , biology , opioid , endocrinology , hyperalgesia , opioid peptide , central nervous system , biochemistry , receptor
1 Whole‐cell patch clamp recordings were made from rat rostral ventromedial medulla (RVM) neurons in vitro to investigate the cellular actions of the opioid‐like receptor ORL1 (NOP), ligand nociceptin/orphanin FQ and other putative prepronociceptin products. 2 Primary and secondary RVM neurons were identified as responding to the κ‐opioid receptor agonist U‐69593 (300 n m to 1 μ m ) and the μ‐ and δ‐opioid receptor agonist met‐enkephalin (10 μ m ), respectively. Both primary and secondary RVM neurons responded to nociceptin (3 n m to 1 μ m ) with an outward current that reversed polarity at –115 mV in brain slices and with inhibition of Ca 2+ channel currents in acutely isolated cells. 3 The putative ORL1 antagonist J‐113397 (1 μ m ) produced no change in membrane current and abolished the outward current produced by nociceptin (100 n m ). In contrast, Phe 1 ψ(CH 2 ‐NH)Gly 2 ]‐nociceptin‐(1‐13)NH 2 (300 n m to 1 μ m ) alone produced an outward current and partially reduced the outward current produced by nociceptin (300 n m ) when co‐applied. 4 In brain slices nociceptin (300 n m ) reduced the amplitude of evoked GABA A receptor‐mediated inhibitory postsynaptic currents (IPSCs) but not non‐NMDA receptor‐mediated excitatory postsynaptic currents (EPSCs). 5 Met‐enkephalin (10 μ m ), but not nociceptin (300 n m ), reduced the rate of spontaneous miniature IPSCs in normal external potassium solution (K + 2.5 m m ). In high external potassium (K + 17.5 m m ), nociceptin reduced the rate of miniature IPSCs in the presence (Ca 2+ 2.4 m m , Mg 2+ 1.2 m m ) but not in the absence of external calcium (Ca 2+ 0 m m , Mg 2+ 10 m m , Cd 2+ 10 μ m ). Nociceptin and met‐enkephalin had no effect on the amplitude of miniature IPSCs. 6 The putative nociceptin precursor products nocistatin (rat prepronociceptin 125–132 ) and rat prepronociceptin 154–181 had no effect on membrane currents, evoked IPSCs and evoked EPSCs. 7 These results indicate that nociceptin acts via the ORL1 receptor to directly inhibit both primary and secondary RVM neurons by activating a potassium conductance and by inhibiting calcium conductances. In addition, nociceptin inhibits GABA release within the RVM via a presynaptic Ca 2+ ‐dependent mechanism. Thus, nociceptin has the potential to exert both disinhibitory and inhibitory effects on neuronal action potential firing within the RVM.