| | |  | | | | Record from Web of Science® | | | | | | |
| Agonist-independent modulation of N-type calcium channels by ORL1 receptors |
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| Author(s): Beedle AM, McRory JE, Poirot O, Doering CJ, Altier C, Barrere C, Hamid J, Nargeot J, Bourinet E, Zamponi GW |
| Source: NATURE NEUROSCIENCE Volume: 7 Issue: 2 Pages: 118-125 Published: FEB 2004 |
| Times Cited: 51 References: 50 |
| Abstract: We have investigated modulation of voltage-gated calcium channels by nociceptin (ORL1) receptors. In rat DRG neurons and in tsA-201 cells, nociceptin mediated a pronounced inhibition of N-type calcium channels, whereas other calcium channel subtypes were unaffected. In tsA-201 cells, expression of N-type channels with human ORL1 resulted in a voltage-dependent G-protein inhibition of the channel that occurred in the absence of nociceptin, the ORL1 receptor agonist. Consistent with this observation, native N-type channels of small nociceptive dorsal root ganglion (DRG) neurons also had tonic inhibition by G proteins. Biochemical characterization showed the existence of an N-type calcium channel-ORL1 receptor signaling complex, which efficiently exposes N-type channels to constitutive ORL1 receptor activity. Calcium channel activity is thus regulated by changes in ORL1 receptor expression, which provides a possible molecular mechanism for the development of tolerance to opioid receptor agonists. |
| Document Type: Article |
| Language: English |
| Reprint Address: Zamponi, GW (reprint author), Univ Calgary, Dept Physiol & Biophys, Cellular & Mol Neurobiol Res Grp, 3330 Hosp Dr NW, Calgary, AB T2N 4N1 Canada |
Addresses:
1. Univ Calgary, Dept Physiol & Biophys, Cellular & Mol Neurobiol Res Grp, Calgary, AB T2N 4N1 Canada
2. CNRS, UPR2580, LGF, Dept Physiol, F-34396 Montpellier, France |
| Publisher: NATURE PUBLISHING GROUP, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Neurosciences |
| IDS Number: 767TJ |
| ISSN: 1097-6256 |
| DOI: 10.1038/nn1180 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |