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 receptor antagonist [Phe1psi(CH(2)-NH)Gly(2)]-nociceptin-(1 - 13)NH(2) (Phe(1)psi-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. 2. 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)psi-nociceptin(1 - 13) also inhibited I(Ba) in LC neurons (notional pD(2) of 7.6, maximum inhibition 18%). Application of Phe(1)psi-nociceptin(1 - 13) (1 microM) significantly occluded the subsequent effects 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, maximum current 50% of that of methionine enkephalin, 10 microM). The Phe(1)psi-nociceptin(1 - 13) induced current reversed polarity at -112 mV and exhibited pronounced inward rectification. Phe(1)psi-nociceptin(1 - 13) (1 microM) reversibly inhibited the current caused by nociceptin (300 nM) by 30%. 4. 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. 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 cells.
Connor
M
M
Department of Pharmacology, The University of Sydney, Sydney 2006, NSW, Australia. markc@pharmacol.usyd.edu.au
Vaughan
C W
CW
Jennings
E A
EA
Allen
R G
RG
Christie
M J
MJ
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D005260:Female; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009292:Narcotic Antagonists; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018847:Opioid Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011498:Protein Precursors; D051381:Rats; D011957:Receptors, Opioid / Q000819:agonists*; D014665:Vasodilator Agents / Q000494:pharmacology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D015220:Calcium Channels; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D015221:Potassium Channels; D011498:Protein Precursors; D011957:Receptors, Opioid; D014665:Vasodilator Agents; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C114149:nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-; C111148:nocistatin; C121527:prepronociceptin; C000722285:Oprl1 protein, rat