Inhibition of Ca2+ channel current by μ‐ and κ‐opioid receptors coexpressed in Xenopus oocytes: desensitization dependence on Ca2+ channel α1 subunits

Kaneko, Shuji; Yada, Nobumichi; Fukuda, Koichiro; Kikuwaka, Masanobu; Akaike, Akinori; Satoh, Masamichi

doi:10.1038/sj.bjp.0701181

Cited by 12 publications

(8 citation statements)

References 36 publications

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“…This report demonstrated that, similar to μ, κ and δ opioid receptors (Nomura et al . 1994; Kaneko et al . 1997; Morikawa et al .…”

Section: Discussionmentioning

confidence: 99%

Acute desensitization of nociceptin/orphanin FQ inhibition of voltage‐gated calcium channels in freshly dissociated hippocampal neurons

Bao

et al. 1999

Eur J of Neuroscience

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Nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for opioid receptor-like receptor, has been shown to inhibit high-voltage-gated calcium channels (VGCCs) in acutely dissociated rat hippocampal pyramidal cells [Knoflach, F., Reinscheid, R.K., Civelli, O. & Kemp, J.A. (1996), J. Neurosci., 16, 6657]. In this study, it was further demonstrated that N/OFQ inhibition of calcium channel current was blocked by its specific antagonist PGN, [Phe1-psi(CH2-NH)-Gly2]nociceptin (1-13)-NH2, and the EC50 of the N/OFQ inhibition was approximately 10 nM, indicating that this effect was really mediated via the opioid receptor-like receptor. The N/OFQ inhibition of the calcium channel current was significantly reduced, as the maximal inhibition decreased from 36 to 23%, by 1-min pretreatment of freshly dissociated hippocampal neurons with the same peptide. The inhibition completely recovered from this acute desensitization in less than 20 min. The N/OFQ inhibition was also greatly attenuated by pretreatment of the neurons with the GABAB (gamma-aminobutyric acid) agonist baclofen while the baclofen inhibition of the calcium channel current was significantly reduced by N/OFQ pretreatment, revealing the agonist-induced desensitization was heterologous in nature. This desensitization was blocked by pretreating the neurons with the sodium channel blocker, tetrodotoxin (TTX), or by removing the extracellular calcium, which indicates the necessity of membrane depolarization and extracellular calcium influx in the process. Furthermore, pretreatment of the neurons with the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), attenuated the N/OFQ inhibition of the calcium channel current whereas the cAMP-dependent kinase A activator, forskolin, showed no effect, suggesting the probable involvement of PKC in the N/OFQ-induced desensitization.

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“…This report demonstrated that, similar to μ, κ and δ opioid receptors (Nomura et al . 1994; Kaneko et al . 1997; Morikawa et al .…”

Section: Discussionmentioning

confidence: 99%

Acute desensitization of nociceptin/orphanin FQ inhibition of voltage‐gated calcium channels in freshly dissociated hippocampal neurons

Bao

et al. 1999

Eur J of Neuroscience

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“…[17][18][19][20][21], in cells expressing various combinations of receptors. Functional N-type calcium channels were reconstituted by expression of Ca v 2.2 along with auxiliary ␣ 2 ␦ 1 and ␤ 1b subunits, and their electrical activity was examined using whole cell patch clamp recordings with 20 mM barium as the charge carrier.…”

Section: Orl1 Receptors Biochemically Interact With Members Of Thementioning

confidence: 99%

Heterodimerization of ORL1 and Opioid Receptors and Its Consequences for N-type Calcium Channel Regulation

Evans

You

Hameed

et al. 2010

Journal of Biological Chemistry

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We have investigated the heterodimerization of ORL1 receptors and classical members of the opioid receptor family. All three classes of opioid receptors could be co-immunoprecipitated with ORL1 receptors from both transfected tsA-201 cell lysate and rat dorsal root ganglia lysate, suggesting that these receptors can form heterodimers. Consistent with this hypothesis, in cells expressing either one of the opioid receptors together with ORL1, prolonged ORL1 receptor activation via nociceptin application resulted in internalization of the opioid receptors. Conversely, -, ␦-, and -opioid receptor activation with the appropriate ligands triggered the internalization of ORL1. The -opioid receptor/ORL1 receptor heterodimers were shown to associate with N-type calcium channels, with activation of -opioid receptors triggering N-type channel internalization, but only in the presence of ORL1. Furthermore, the formation of opioid receptor/ORL1 receptor heterodimers attenuated the ORL1 receptor-mediated inhibition of N-type channels, in part because of constitutive opioid receptor activity. Collectively, our data support the existence of heterodimers between ORL1 and classical opioid receptors, with profound implications for effectors such as N-type calcium channels.ORL1 (opioid receptor-like 1) receptors (also known as NOP or nociceptin receptors) belong to the class of G␣ i/o -linked seven-helix transmembrane receptors (1, 2). They are structurally related to members of the classical opioid receptor family (i.e. -, ␦-, and -opioid receptors) but do not interact with known opioid receptor agonists or antagonists. Instead, they are activated by the endogenous ligand orphanin FQ (also known as nociceptin), a 17-amino acid polypeptide (3). ORL1 receptors are expressed in both the central and peripheral nervous systems; the physiological effects of receptor activation include stimulation of food intake, reduced anxiety, reduced withdrawal symptoms, and when activated peripherally, analgesia (4 -6). There is a functional cross-talk between ORL1 receptors and -opioid receptors such that chronic administration of the -receptor agonist morphine results in increased ORL1 receptor expression levels (7), whereas knock-out of the ORL1 receptor gene results in decreased morphine tolerance (8) without compensatory changes in opioid receptor expression (9). This may hint at the possibility of overlapping mechanisms controlling cellular expression levels of these two receptor subtypes.We have recently shown that ORL1 receptors physically interact with N-type calcium channels and that this interaction results in two distinct consequences: first, an agonist-independent inhibition of N-type channels due to constitutive receptor activity (10), and second, receptor-mediated trafficking of N-type channels to and from the plasma membrane (11). Neither of these phenomena appeared to occur with -opioid receptors (11). ORL1 receptors have also been shown to heterodimerize with -opioid receptors (12), with dimerized receptors showing altered sensitiv...

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“…Desensitization and down‐regulation each occur with their own characteristic time course. Desensitization occurs within minutes of agonist exposure, and down‐regulation follows the former in periods ranging from hours to days (Chakrabarti et al, 1995 ; Kovoor et al, 1995 ; Zhang et al, 1996 ; Breivogel et al, 1997 ; Kaneko et al, 1997). Desensitization is a rapid, reversible loss of agonist affinity and receptor function, produced by an uncoupling of the receptor from its G protein (Harada et al, 1990 ; Hausdorff et al, 1990 ; Harrington et al, 1994).…”

mentioning

confidence: 99%

Role of Protein Kinase C (PKC) in Agonist‐Induced μ‐Opioid Receptor Down‐Regulation

Ej²

1999

Journal of Neurochemistry

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Phosphorylation of specific amino acid residues is believed to be crucial for the agonist-induced regulation of several G protein-coupled receptors. This is especially true for the three types of opioid receptors (, , and), which contain consensus sites for phosphory-lation by numerous protein kinases. Protein kinase C (PKC) has been shown to catalyze the in vitro phosphor-ylation of-and-opioid receptors and to potentiate agonist-induced receptor desensitization. In this series of experiments, we continue our investigation of how opi-oid-activated PKC contributes to homologous receptor down-regulation and then expand our focus to include the exploration of the mechanism(s) by which-opioids produce PKC translocation in SH-SY5Y neuroblastoma cells. [D-Ala 2 ,N-Me-Phe 4 ,Gly-ol]enkephalin (DAMGO)-induced PKC translocation follows a time-dependent and biphasic pattern beginning 2 h after opioid addition, when a pronounced translocation of PKC to the plasma membrane occurs. When opioid exposure is lengthened to 12 h, both cytosolic and particulate PKC levels drop significantly below those of control-treated cells in a process we termed "reverse translocation." The opioid receptor antagonist naloxone, the PKC inhibitor cheleryth-rine, and the L-type calcium channel antagonist nimodip-ine attenuated opioid-mediated effects on PKC and-receptor down-regulation, suggesting that this is a process partially regulated by Ca 2-dependent PKC iso-forms. However, chronic exposure to phorbol ester, which depletes the cells of diacylglycerol (DAG) and Ca 2-sensitive PKC isoforms, before DAMGO exposure, had no effect on opioid receptor down-regulation. In addition to expressing conventional (PKC-) and novel (PKC-) isoforms, SH-SY5Y cells also contain a DAG-and Ca 2-independent, atypical PKC isozyme (PKC-), which does not decrease in expression after prolonged DAMGO or phorbol ester treatment. This led us to investigate whether PKC-is similarly sensitive to activation by-opioids. PKC-translocates from the cytosol to the membrane with kinetics similar to those of PKC-and in response to DAMGO but does not undergo reverse translocation after longer exposure times. Our evidence suggests that direct PKC activation by-opioid agonists is involved in the processes that result in-receptor down-regulation in human neuroblastoma cells and that conventional, novel, and atypical PKC isozymes are involved. Key Words: Protein kinase-Receptor-Down-regulation-Second messenger-Isoenzyme. J. Neurochem. 72, 594-604 (1999). The recent cloning of the major opioid receptor types (, , and) has provided essential information about their plasticity (Evans et al., 1992; Kieffer et al., 1992; Chen et al., 1993; Wang et al., 1993; Yasuda et al., 1993). Repeated or prolonged exposure to opioid ago-nists reduces the responsiveness of opioid receptors to its agonists over time. This loss of receptor function is hypothesized to contribute to the cellular and biochemical changes that lead to opiate tolerance, dependence, and, possibly, addiction in humans (Nestler, ...

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Inhibition of Ca²⁺ channel current by μ‐ and κ‐opioid receptors coexpressed in Xenopus oocytes: desensitization dependence on Ca²⁺ channel α₁ subunits

Cited by 12 publications

References 36 publications

Acute desensitization of nociceptin/orphanin FQ inhibition of voltage‐gated calcium channels in freshly dissociated hippocampal neurons

Acute desensitization of nociceptin/orphanin FQ inhibition of voltage‐gated calcium channels in freshly dissociated hippocampal neurons

Heterodimerization of ORL1 and Opioid Receptors and Its Consequences for N-type Calcium Channel Regulation

Role of Protein Kinase C (PKC) in Agonist‐Induced μ‐Opioid Receptor Down‐Regulation

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