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Nociceptin, Phe 1 ψ‐nociceptin 1–13 , nocistatin and prepronociceptin 154–181 effects on calcium channel currents and a potassium current in rat locus coeruleus in vitro

1999; Wiley; Volume: 128; Issue: 8 Linguagem: Inglês

10.1038/sj.bjp.0702971

1476-5381

Mark Connor, Christopher W. Vaughan, Ernest Jennings, Richard G. Allen, MacDonald J. Christie,

Hypothalamic control of reproductive hormones

The actions of the neuropeptide nociceptin, the putative nociceptin receptor antagonist [Phe1ψ(CH 2 ‐NH)Gly 2 ]‐nociceptin‐(1–13)NH 2 (Phe 1 ψ‐nociceptin 1–13 ) and the putative nociceptin precursor products nocistatin (rat prepronociceptin 125–132 ) and rat prepronociceptin 154–181 were examined on membrane properties of rat locus coeruleus (LC) neurons using whole cell patch clamp techniques. Nociceptin inhibited I Ba in all LC neurons, ( pD 2 of 8.9, maximum inhibition 50%). The inhibition of I Ba by nociceptin was associated with slowing of the activation of I Ba and could be significantly reversed by a strong depolarizing prepulse. Phe 1 ψ‐nociceptin 1–13 also inhibited I Ba in LC neurons (notional pD 2 of 7.6, maximum inhibition 18%). Application of Phe 1 ψ‐nociceptin 1–13 (1 μ M ) significantly occluded the subsequent effects of a co‐application of nociceptin (3 n M ) on I Ba . As previously reported for nociceptin, Phe 1 ψ‐nociceptin 1–13 caused an outward current in LC neurons voltage clamped at −60 mV ( pD 2 of 7.1, maximum current 50% of that of methionine enkephalin, 10 μ M ). The Phe 1 ψ‐nociceptin 1–13 induced current reversed polarity at −112 mV and exhibited pronounced inward rectification. Phe 1 ψ‐nociceptin 1–13 (1 μ M ) reversibly inhibited the current caused by nociceptin (300 n M ) by 30%. Neither nocistatin nor rat prepronociceptin 154–181 inhibited I Ba in LC neurons, or prevented the subsequent inhibition by nociceptin. Neither nocistatin or prepronociceptin 154–181 affected the membrane properties of LC neurons. This study demonstrates that nociceptin modulates somatic I Ba in rat LC neurons. The putative ORL1 antagonist Phe 1 ψ‐nociceptin 1–13 exhibited partial agonist activity at inhibiting I Ba and opening K + channels in LC. Other putative nociceptin precursor products were without effect on LC cells. British Journal of Pharmacology (1999) 128 , 1779–1787; doi: 10.1038/sj.bjp.0702971