Nociceptin, Phe(1)psi-nociceptin(1-13), nocistatin and prepronociceptin(154-181) effects on calcium channel currents and a potassium current in rat locus coeruleus in vitro

1 The actions of the neuropeptide nociceptin, the putative nociceptin recep tor antagonist [Phe1 psi(CH2-NH)Gly(2)]-nociceptin-(1 - 13)NH2 (Phe(1)psi-n ociceptin(1-13)) and the putative nociceptin precursor products nocistatin (rat prepronociceptin(125-132)) and rat prepronociceptin(154-181) were exam ined on membrane properties of rat locus coeruleus (LC) neurons using whole cell patch clamp techniques. 2 Nociceptin inhibited I-Ba in all LC neurons, (pD(2) of 8.9, maximum inhib ition 50%). The inhibition of I-Ba by nociceptin was associated with slowin g of the activation of I-Ba and could be significantly reversed by a strong depolarizing prepulse. Phe(1)psi-nociceptin(1-13) also inhibited I-Ba in L C neurons (notional pD(2) of 7.6, maximum inhibition 18%). Application of P he(1)psi-nociceptin(1-13) (1 mu M) significantly occluded the subsequent ef fects of a co-application of nociceptin (3 nM) on I-Ba. 3 As previously reported for nociceptin, Phe(1)psi-nociceptin(1-13) caused an outward current in LC neurons voltage clamped at -60 mV (pD(2) of 7.1, m aximum current 50% of that of methionine enkephalin, 10 mu M). The Phe(1)ps i-nociceptin(1-13) induced current reversed polarity at -112 mV and exhibit ed pronounced inward rectification. Phe(1)psi-nociceptin(1-13) (1 mu M) rev ersibly inhibited the current caused by nociceptin (300 nhl) by 30%. 4 Neither nocistatin nor rat prepronociceptin(154-181) inhibited I-Ba in LC neurons, or prevented the subsequent inhibition by nociceptin. Neither noc istatin or prepronociceptin(154-181) affected the membrane properties of LC neurons. 5 This study demonstrates that nociceptin modulates somatic I-Ba in rat LC neurons. The putative ORL1 antagonist Phe(1)psi-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 cell s.