 |
 Previous Article | Next Article 
Volume 16, Number 21,
Issue of November 1, 1996
pp. 6657-6664
Copyright ©1996 Society for Neuroscience
Modulation of Voltage-Gated Calcium Channels by Orphanin FQ in
Freshly Dissociated Hippocampal Neurons
Received June 5, 1996; revised Aug. 6, 1996; accepted Aug. 9, 1996.
Frederic Knoflach,
Rainer K. Reinscheid,
Olivier Civelli, and
John A. Kemp
F. Hoffmann-La Roche Ltd., Pharma Division, Preclinical Research,
CH-4070 Basel, Switzerland
Orphanin FQ (OFQ) has recently been reported to be an endogenous
ligand for the opioid-like LC132 receptor. The effect of OFQ on high
voltage-gated calcium channels (VGCCs) was examined in freshly
dissociated rat pyramidal neurons using the whole-cell configuration of
the patch-clamp technique. High-threshold Ba2+ currents
were reversibly inhibited by OFQ. The depression of the currents was
associated with a slowed rate of activation and a change in the
activation I-V relationship at step
potentials higher than +30 mV. In concentration-response experiments,
a mean (±SEM) pEC50 value of 7.0 ± 0.07 and a Hill
coefficient of 1.5 ± 0.08 (n = 5) were
obtained. The near-maximum inhibition of the Ba2+ currents
by OFQ (1 µM) amounted to 31 ± 2.2% of control
(n = 15). Opioid receptors could not account for
the effects of OFQ on VGCCs, because naloxone, a broad spectrum µ-,
 -, and  -receptor antagonist, did not reduce the effectiveness of
OFQ. When GTP- -S was included in the pipette, the depression of the
currents by OFQ was irreversible, whereas currents from neurons
preincubated with pertussis toxin were not inhibited by OFQ, consistent
with the involvement of a PTX-sensitive G-protein. When selective
blockers of VGCCs were used, it was demonstrated that all subtypes of
VGCCs were affected by OFQ. In conclusion, the effect of OFQ on VGCCs
expressed in hippocampal CA3 and CA1 neurons may play an important role
in the regulation of hippocampal cell excitability and neurotransmitter
release.
Key words:
calcium channel blockers;
calcium channel drug
effects;
opioid drug effects;
G-protein;
patch clamp;
nifedipine;
 -conotoxin-GVIA;
-agatoxin-IVA;
GTP--S;
orphanin FQ;
nociceptin;
opioid receptor;
neuromodulation
This article has been cited by other articles:
|
|
|
|
 
S. Chung, S. Pohl, J. Zeng, O. Civelli, and R. K. Reinscheid
Endogenous Orphanin FQ/Nociceptin Is Involved in the Development of Morphine Tolerance
J. Pharmacol. Exp. Ther.,
July 1, 2006;
318(1):
262 - 267.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Ruiz-Velasco, H. L. Puhl, B. C. Fuller, and A. D. Sumner
Modulation of Ca2+ Channels by Opioid Receptor-Like 1 Receptors Natively Expressed in Rat Stellate Ganglion Neurons Innervating Cardiac Muscle
J. Pharmacol. Exp. Ther.,
September 1, 2005;
314(3):
987 - 994.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Orsini, I. Nesmelova, H. C. Young, B. Hargittai, M. P. Beavers, J. Liu, P. J. Connolly, S. A. Middleton, and K. H. Mayo
The Nociceptin Pharmacophore Site for Opioid Receptor Binding Derived from the NMR Structure and Bioactivity Relationships
J. Biol. Chem.,
March 4, 2005;
280(9):
8134 - 8142.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. K. Olszewski and A. S. Levine
Minireview: Characterization of Influence of Central Nociceptin/Orphanin FQ on Consummatory Behavior
Endocrinology,
June 1, 2004;
145(6):
2627 - 2632.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. F. Zaratin, G. Petrone, M. Sbacchi, M. Garnier, C. Fossati, P. Petrillo, S. Ronzoni, G. A. M. Giardina, and M. A. Scheideler
J. Pharmacol. Exp. Ther.,
February 1, 2004;
308(2):
454 - 461.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Meis
Nociceptin/Orphanin FQ: Actions within the Brain
Neuroscientist,
April 1, 2003;
9(2):
158 - 168.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. H. Chin, K. Harris, D. MacTavish, and J. H. Jhamandas
Nociceptin/Orphanin FQ Modulation of Ionic Conductances in Rat Basal Forebrain Neurons
J. Pharmacol. Exp. Ther.,
October 1, 2002;
303(1):
188 - 195.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Katsura, Y. Mohri, K. Shuto, Y. Hai-Du, T. Amano, A. Tsujimura, M. Sasa, and S. Ohkuma
Up-regulation of L-type Voltage-dependent Calcium Channels after Long Term Exposure to Nicotine in Cerebral Cortical Neurons
J. Biol. Chem.,
March 1, 2002;
277(10):
7979 - 7988.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Venkatesan, J. Wang, C. Evans, M. Irnaten, and D. Mendelowitz
Nociceptin Inhibits gamma -Aminobutyric Acidergic Inputs to Cardiac Parasympathetic Neurons in the Nucleus Ambiguus
J. Pharmacol. Exp. Ther.,
January 1, 2002;
300(1):
78 - 82.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Knoflach, V. Mutel, S. Jolidon, J. N. C. Kew, P. Malherbe, E. Vieira, J. Wichmann, and J. A. Kemp
Positive allosteric modulators of metabotropic glutamate 1 receptor: Characterization, mechanism of action, and binding site
PNAS,
October 16, 2001;
(2001)
231358298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Mogil and G. W. Pasternak
The Molecular and Behavioral Pharmacology of the Orphanin FQ/Nociceptin Peptide and Receptor Family
Pharmacol. Rev.,
September 1, 2001;
53(3):
381 - 415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. M. Dautzenberg, J. Wichmann, J. Higelin, G. Py-Lang, C. Kratzeisen, P. Malherbe, G. J. Kilpatrick, and F. Jenck
Pharmacological Characterization of the Novel Nonpeptide Orphanin FQ/Nociceptin Receptor Agonist Ro 64-6198: Rapid and Reversible Desensitization of the ORL1 Receptor in Vitro and Lack of Tolerance in Vivo
J. Pharmacol. Exp. Ther.,
August 1, 2001;
298(2):
812 - 819.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Liu, H.-Z. Hu, J. Ren, C. Gao, N. Gao, Z. Lin, Y. Xia, and J. D. Wood
Pre- and postsynaptic inhibition by nociceptin in guinea pig small intestinal myenteric plexus in vitro
Am J Physiol Gastrointest Liver Physiol,
July 1, 2001;
281(1):
G237 - G246.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Madamba, P. Schweitzer, and G. R. Siggins
Nociceptin Augments K+ Currents in Hippocampal CA1 Neurons by Both ORL-1 and Opiate Receptor Mechanisms
J Neurophysiol,
October 1, 1999;
82(4):
1776 - 1785.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-Z. Wei and C.-W. Xie
Orphanin FQ Suppresses NMDA Receptor-Dependent Long-Term Depression and Depotentiation in Hippocampal Dentate Gyrus
Learn. Mem.,
September 1, 1999;
6(5):
467 - 477.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Wnendt, T. Krüger, E. Janocha, D. Hildebrandt, and W. Englberger
Agonistic Effect of Buprenorphine in a Nociceptin/OFQ Receptor-Triggered Reporter Gene Assay
Mol. Pharmacol.,
August 1, 1999;
56(2):
334 - 338.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Meis and H.-C. Pape
Postsynaptic Mechanisms Underlying Responsiveness of Amygdaloid Neurons to Nociceptin/Orphanin FQ
J. Neurosci.,
October 15, 1998;
18(20):
8133 - 8144.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T.-P. Yu and C.-W. Xie
Orphanin FQ/Nociceptin Inhibits Synaptic Transmission and Long-Term Potentiation in Rat Dentate Gyrus Through Postsynaptic Mechanisms
J Neurophysiol,
September 1, 1998;
80(3):
1277 - 1284.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Zaki and C. J. Evans
{blacksquare} REVIEW : ORL-1: An Awkward Child of the Opioid Receptor Family
Neuroscientist,
May 1, 1998;
4(3):
172 - 184.
[Abstract]
[PDF]
|
|
|
|
|
|
|
F. Jenck, J.-L. Moreau, J. R. Martin, G. J. Kilpatrick, R. K. Reinscheid, F. J. Monsma Jr., H.-P. Nothacker, and O. Civelli
Orphanin FQ acts as an anxiolytic to attenuate behavioral responses to stress
PNAS,
December 23, 1997;
94(26):
14854 - 14858.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. A. Abdulla and P. A. Smith
Nociceptin Inhibits T-Type Ca2+ Channel Current in Rat Sensory Neurons by a G-Protein-Independent Mechanism
J. Neurosci.,
November 15, 1997;
17(22):
8721 - 8728.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Knoflach, V. Mutel, S. Jolidon, J. N. C. Kew, P. Malherbe, E. Vieira, J. Wichmann, and J. A. Kemp
Positive allosteric modulators of metabotropic glutamate 1 receptor: Characterization, mechanism of action, and binding site
PNAS,
November 6, 2001;
98(23):
13402 - 13407.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
