The Experts below are selected from a list of 210 Experts worldwide ranked by ideXlab platform
Tsutomu Suzuki - One of the best experts on this subject based on the ideXlab platform.
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Functional interaction among opioid receptor types: up-regulation of μ- and δ-opioid receptor functions after Repeated Stimulation of κ-opioid receptors
Neuropharmacology, 2004Co-Authors: Junaidi Khotib, Minoru Narita, Yoshinori Yajima, Masami Suzuki, Tsutomu SuzukiAbstract:It has been widely accepted that Repeated administration of kappa-opioid receptor agonists leads to the development of antinociceptive tolerance. The present study was designed to investigate the effect of Repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride ((-)U-50,488H) on the mu- and delta-opioid receptor agonist-induced antinociception and G-protein activation in mice. The mice were injected either subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) pretreated with saline or (-)U-50,488H once a day for seven consecutive days. Two hours after the last injection, the mice were challenged by either mu- or delta-opioid receptor agonist for the antinociceptive assay. Repeated treatment with (-)U-50,488H (s.c. or i.c.v.) significantly enhanced antinociceptive effect of both mu-opioid receptor agonist (morphine) and delta-opioid receptor agonists ([d-Ala2]deltorphin (DELT) and (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dime thyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80) compared to saline-treated groups. Under these conditions, Repeated s.c. injection of (-)U-50,488H significantly enhanced both mu- and delta-opioid receptor agonist-stimulated [35S]GTPgammaS binding in the membrane of the thalamus. On the contrary, either Repeated administration of morphine (s.c. or i.c.v.) or SNC-80 failed to affect the kappa-opioid receptor agonist-induced antinociception and G-protein activation. Taken together, these results suggest that Repeated Stimulation of kappa-opioid receptor markedly increases the functional mu- and delta-opioid receptors, whereas Repeated Stimulation of either mu- or delta-opioid receptor had no direct effect on kappa-opioidergic function in mice.
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Functional interaction among opioid receptor types: up-regulation of μ- and δ-opioid receptor functions after Repeated Stimulation of κ-opioid receptors
Neuropharmacology, 2004Co-Authors: Junaidi Khotib, Minoru Narita, Yoshinori Yajima, Masami Suzuki, Tsutomu SuzukiAbstract:It has been widely accepted that Repeated administration of kappa-opioid receptor agonists leads to the development of antinociceptive tolerance. The present study was designed to investigate the effect of Repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride ((-)U-50,488H) on the mu- and delta-opioid receptor agonist-induced antinociception and G-protein activation in mice. The mice were injected either subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) pretreated with saline or (-)U-50,488H once a day for seven consecutive days. Two hours after the last injection, the mice were challenged by either mu- or delta-opioid receptor agonist for the antinociceptive assay. Repeated treatment with (-)U-50,488H (s.c. or i.c.v.) significantly enhanced antinociceptive effect of both mu-opioid receptor agonist (morphine) and delta-opioid receptor agonists ([d-Ala2]deltorphin (DELT) and (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dime thyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80) compared to saline-treated groups. Under these conditions, Repeated s.c. injection of (-)U-50,488H significantly enhanced both mu- and delta-opioid receptor agonist-stimulated [35S]GTPgammaS binding in the membrane of the thalamus. On the contrary, either Repeated administration of morphine (s.c. or i.c.v.) or SNC-80 failed to affect the kappa-opioid receptor agonist-induced antinociception and G-protein activation. Taken together, these results suggest that Repeated Stimulation of kappa-opioid receptor markedly increases the functional mu- and delta-opioid receptors, whereas Repeated Stimulation of either mu- or delta-opioid receptor had no direct effect on kappa-opioidergic function in mice.
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Heterologous mu-opioid receptor adaptation by Repeated Stimulation of kappa-opioid receptor: up-regulation of G-protein activation and antinociception.
Journal of neurochemistry, 2003Co-Authors: Minoru Narita, Yoshinori Yajima, Masami Suzuki, Junaidi Khotib, Satoru Ozaki, Tsutomu SuzukiAbstract:The present study was designed to investigate the effect of Repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride [(-)U-50,488H] on antinociception and G-protein activation induced by mu-opioid receptor agonists in mice. A single s.c. injection of (-)U-50,488H produced a dose-dependent antinociception, and this effect was reversed by a selective kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI). Furthermore, a single s.c. pre-treatment with (-)U-50,488H had no effect on the mu-opioid receptor agonist-induced antinociception. In contrast, Repeated s.c. administration of (-)U-50,488H resulted in the development of tolerance to (-)U-50,488H-induced antinociception. Under these conditions, we demonstrated here that Repeated s.c. injection of (-)U-50,488H significantly enhanced the antinociceptive effect of selective mu-opioid receptor agonists endomorphin-1, endomorphin-2 and [d-Ala2,N-MePhe4,Gly-ol5] enkephalin (DAMGO). Using the guanosine-5'-o-(3-[35S]thio) triphosphate ([35S]GTP gamma S) binding assay, we found that (-)U-50,488H was able to produce a nor-BNI-reversible increase in [35S]GTP gamma S binding to membranes of the mouse thalamus, which has a high level of kappa-opioid receptors. Repeated administration of (-)U-50,488H caused a significant reduction in the (-)U-50,488H-stimulated [35S]GTP gamma S binding in this region, whereas chronic treatment with (-)U-50,488H exhibited the increase in the endomorphin-1-, endomorphin-2- and DAMGO-stimulated [35S]GTP gamma S bindings in membranes of the thalamus and periaqueductal gray. These results suggest that Repeated Stimulation of kappa-opioid receptors leads to the heterologous up-regulation of mu-opioid receptor functions in the thalamus and periaqueductal gray regions, which may be associated with the supersensitivity of mu-opioid receptor-mediated antinociception.
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Direct evidence for the up‐regulation of spinal µ‐opioid receptor function after Repeated Stimulation of κ‐opioid receptors in the mouse
The European journal of neuroscience, 2003Co-Authors: Minoru Narita, Yoshinori Yajima, Masami Suzuki, Junaidi Khotib, Satoru Ozaki, Hirokazu Mizoguchi, Leon F. Tseng, Tsutomu SuzukiAbstract:The present study was designed to investigate the possible change in spinal micro -opioid receptor function after Repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]-benzeneacetamide hydrochloride [(-)U-50,488H] in the ICR mouse. A single s.c. or i.t. injection of (-)U-50,488H produced a dose-dependent antinociception. Repeated s.c. or i.t. administration of (-)U-50,488H resulted in the development of tolerance to (-)U-50,488H-induced antinociception. Under these conditions, we demonstrated here that Repeated s.c. injection of (-)U-50,488H significantly enhanced the antinociceptive effect induced by the i.t. administration of a selective micro -opioid receptor agonist [d-Ala2,N-Me-Phe4,Gly5-ol] enkephalin (DAMGO). Using the guanosine-5'-o-(3-[35S]thio) triphosphate ([35S]GTPgammaS) binding assay, we found that (-)U-50,488H was able to produce a dose-dependent increase in [35S]GTPgammaS binding to membranes of the mouse spinal cord. Repeated administration of (-)U-50,488H caused a significant reduction in the (-)U-50,488H-stimulated [35S]GTPgammaS binding in this region, whereas Repeated treatment with (-)U-50,488H exhibited an increase in the DAMGO-stimulated [35S]GTPgammaS binding in membranes of the spinal cord. Using a receptor binding assay, Repeated treatment with (-)U-50,488H significantly increased the density of [3H]DAMGO binding sites in membranes of the mouse spinal cord. In contrast, the expression of micro -opioid receptor was not affected after Repeated treatment with (-)U-50,488H. These results suggest that Repeated Stimulation of kappa-opioid receptors leads to the up-regulation of micro -opioid receptor functions in the spinal cord, which may be associated with an increase in the number of functional micro -opioid receptors in the mouse spinal cord.
Julie Perroy - One of the best experts on this subject based on the ideXlab platform.
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Repeated Stimulation of dopamine d1 like receptor and hyperactivation of mtor signaling lead to generalized seizures altered dentate gyrus plasticity and memory deficits
Hippocampus, 2014Co-Authors: Giuseppe Gangarossa, Laura Ceolin, Alexia Paucard, Julie Perroy, Mireille LernernatoliAbstract:The acute activation of the dopamine D1-like receptors (D1R) is involved in a plethora of functions ranging from increased locomotor activity to the facilitation of consolidation, storage, and retrieval of memories. Although much less characterized, epileptiform activities, usually triggered by disruption of the glutamate and GABA balance, have also been reported to involve the dopaminergic trans- mission. Using a combination of biochemical, immunohistochemical, electrophysiological, and behavioral approaches we have investigated the consequences of Repeated Stimulation of D1R using the selective D1R-like agonist SKF81297. Here, we report that Repeated systemic administration of SKF81297 induces kindled seizures in mice. These seizure episodes parallel the hyperactivation of the mTOR signaling in the hippocampus, leading to disrupted long-term potentiation (LTP) in the dentate gyrus (DG) and altered recognition memories. The mTOR inhibitor rapamycin delays the development of SKF81297-induced kindled seizures, and rescues LTP in the DG and object recognition. Our results show that Repeated Stimulation of D1R is sufficient to induce generalized seizures leading to the overactivation of mTOR sig- naling, disrupted hippocampal plasticity, and impaired long-term rec- ognition memories. This work highlights the interest of mTOR inhibitors as therapeutic strategies to reverse plasticity and cognitive deficits. V C 2014 Wiley Periodicals, Inc.
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Repeated Stimulation of dopamine D1‐like receptor and hyperactivation of mTOR signaling lead to generalized seizures, altered dentate gyrus plasticity, and memory deficits
Hippocampus, 2014Co-Authors: Giuseppe Gangarossa, Laura Ceolin, Alexia Paucard, Mireille Lerner-natoli, Julie Perroy, L. Fagni, Emmanuel ValjentAbstract:The acute activation of the dopamine D1-like receptors (D1R) is involved in a plethora of functions ranging from increased locomotor activity to the facilitation of consolidation, storage, and retrieval of memories. Although much less characterized, epileptiform activities, usually triggered by disruption of the glutamate and GABA balance, have also been reported to involve the dopaminergic trans- mission. Using a combination of biochemical, immunohistochemical, electrophysiological, and behavioral approaches we have investigated the consequences of Repeated Stimulation of D1R using the selective D1R-like agonist SKF81297. Here, we report that Repeated systemic administration of SKF81297 induces kindled seizures in mice. These seizure episodes parallel the hyperactivation of the mTOR signaling in the hippocampus, leading to disrupted long-term potentiation (LTP) in the dentate gyrus (DG) and altered recognition memories. The mTOR inhibitor rapamycin delays the development of SKF81297-induced kindled seizures, and rescues LTP in the DG and object recognition. Our results show that Repeated Stimulation of D1R is sufficient to induce generalized seizures leading to the overactivation of mTOR sig- naling, disrupted hippocampal plasticity, and impaired long-term rec- ognition memories. This work highlights the interest of mTOR inhibitors as therapeutic strategies to reverse plasticity and cognitive deficits. V C 2014 Wiley Periodicals, Inc.
Giuseppe Gangarossa - One of the best experts on this subject based on the ideXlab platform.
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Repeated Stimulation of dopamine d1 like receptor and hyperactivation of mtor signaling lead to generalized seizures altered dentate gyrus plasticity and memory deficits
Hippocampus, 2014Co-Authors: Giuseppe Gangarossa, Laura Ceolin, Alexia Paucard, Julie Perroy, Mireille LernernatoliAbstract:The acute activation of the dopamine D1-like receptors (D1R) is involved in a plethora of functions ranging from increased locomotor activity to the facilitation of consolidation, storage, and retrieval of memories. Although much less characterized, epileptiform activities, usually triggered by disruption of the glutamate and GABA balance, have also been reported to involve the dopaminergic trans- mission. Using a combination of biochemical, immunohistochemical, electrophysiological, and behavioral approaches we have investigated the consequences of Repeated Stimulation of D1R using the selective D1R-like agonist SKF81297. Here, we report that Repeated systemic administration of SKF81297 induces kindled seizures in mice. These seizure episodes parallel the hyperactivation of the mTOR signaling in the hippocampus, leading to disrupted long-term potentiation (LTP) in the dentate gyrus (DG) and altered recognition memories. The mTOR inhibitor rapamycin delays the development of SKF81297-induced kindled seizures, and rescues LTP in the DG and object recognition. Our results show that Repeated Stimulation of D1R is sufficient to induce generalized seizures leading to the overactivation of mTOR sig- naling, disrupted hippocampal plasticity, and impaired long-term rec- ognition memories. This work highlights the interest of mTOR inhibitors as therapeutic strategies to reverse plasticity and cognitive deficits. V C 2014 Wiley Periodicals, Inc.
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Repeated Stimulation of dopamine D1‐like receptor and hyperactivation of mTOR signaling lead to generalized seizures, altered dentate gyrus plasticity, and memory deficits
Hippocampus, 2014Co-Authors: Giuseppe Gangarossa, Laura Ceolin, Alexia Paucard, Mireille Lerner-natoli, Julie Perroy, L. Fagni, Emmanuel ValjentAbstract:The acute activation of the dopamine D1-like receptors (D1R) is involved in a plethora of functions ranging from increased locomotor activity to the facilitation of consolidation, storage, and retrieval of memories. Although much less characterized, epileptiform activities, usually triggered by disruption of the glutamate and GABA balance, have also been reported to involve the dopaminergic trans- mission. Using a combination of biochemical, immunohistochemical, electrophysiological, and behavioral approaches we have investigated the consequences of Repeated Stimulation of D1R using the selective D1R-like agonist SKF81297. Here, we report that Repeated systemic administration of SKF81297 induces kindled seizures in mice. These seizure episodes parallel the hyperactivation of the mTOR signaling in the hippocampus, leading to disrupted long-term potentiation (LTP) in the dentate gyrus (DG) and altered recognition memories. The mTOR inhibitor rapamycin delays the development of SKF81297-induced kindled seizures, and rescues LTP in the DG and object recognition. Our results show that Repeated Stimulation of D1R is sufficient to induce generalized seizures leading to the overactivation of mTOR sig- naling, disrupted hippocampal plasticity, and impaired long-term rec- ognition memories. This work highlights the interest of mTOR inhibitors as therapeutic strategies to reverse plasticity and cognitive deficits. V C 2014 Wiley Periodicals, Inc.
Junaidi Khotib - One of the best experts on this subject based on the ideXlab platform.
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Functional interaction among opioid receptor types: up-regulation of μ- and δ-opioid receptor functions after Repeated Stimulation of κ-opioid receptors
Neuropharmacology, 2004Co-Authors: Junaidi Khotib, Minoru Narita, Yoshinori Yajima, Masami Suzuki, Tsutomu SuzukiAbstract:It has been widely accepted that Repeated administration of kappa-opioid receptor agonists leads to the development of antinociceptive tolerance. The present study was designed to investigate the effect of Repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride ((-)U-50,488H) on the mu- and delta-opioid receptor agonist-induced antinociception and G-protein activation in mice. The mice were injected either subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) pretreated with saline or (-)U-50,488H once a day for seven consecutive days. Two hours after the last injection, the mice were challenged by either mu- or delta-opioid receptor agonist for the antinociceptive assay. Repeated treatment with (-)U-50,488H (s.c. or i.c.v.) significantly enhanced antinociceptive effect of both mu-opioid receptor agonist (morphine) and delta-opioid receptor agonists ([d-Ala2]deltorphin (DELT) and (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dime thyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80) compared to saline-treated groups. Under these conditions, Repeated s.c. injection of (-)U-50,488H significantly enhanced both mu- and delta-opioid receptor agonist-stimulated [35S]GTPgammaS binding in the membrane of the thalamus. On the contrary, either Repeated administration of morphine (s.c. or i.c.v.) or SNC-80 failed to affect the kappa-opioid receptor agonist-induced antinociception and G-protein activation. Taken together, these results suggest that Repeated Stimulation of kappa-opioid receptor markedly increases the functional mu- and delta-opioid receptors, whereas Repeated Stimulation of either mu- or delta-opioid receptor had no direct effect on kappa-opioidergic function in mice.
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Functional interaction among opioid receptor types: up-regulation of μ- and δ-opioid receptor functions after Repeated Stimulation of κ-opioid receptors
Neuropharmacology, 2004Co-Authors: Junaidi Khotib, Minoru Narita, Yoshinori Yajima, Masami Suzuki, Tsutomu SuzukiAbstract:It has been widely accepted that Repeated administration of kappa-opioid receptor agonists leads to the development of antinociceptive tolerance. The present study was designed to investigate the effect of Repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride ((-)U-50,488H) on the mu- and delta-opioid receptor agonist-induced antinociception and G-protein activation in mice. The mice were injected either subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) pretreated with saline or (-)U-50,488H once a day for seven consecutive days. Two hours after the last injection, the mice were challenged by either mu- or delta-opioid receptor agonist for the antinociceptive assay. Repeated treatment with (-)U-50,488H (s.c. or i.c.v.) significantly enhanced antinociceptive effect of both mu-opioid receptor agonist (morphine) and delta-opioid receptor agonists ([d-Ala2]deltorphin (DELT) and (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dime thyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80) compared to saline-treated groups. Under these conditions, Repeated s.c. injection of (-)U-50,488H significantly enhanced both mu- and delta-opioid receptor agonist-stimulated [35S]GTPgammaS binding in the membrane of the thalamus. On the contrary, either Repeated administration of morphine (s.c. or i.c.v.) or SNC-80 failed to affect the kappa-opioid receptor agonist-induced antinociception and G-protein activation. Taken together, these results suggest that Repeated Stimulation of kappa-opioid receptor markedly increases the functional mu- and delta-opioid receptors, whereas Repeated Stimulation of either mu- or delta-opioid receptor had no direct effect on kappa-opioidergic function in mice.
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Heterologous mu-opioid receptor adaptation by Repeated Stimulation of kappa-opioid receptor: up-regulation of G-protein activation and antinociception.
Journal of neurochemistry, 2003Co-Authors: Minoru Narita, Yoshinori Yajima, Masami Suzuki, Junaidi Khotib, Satoru Ozaki, Tsutomu SuzukiAbstract:The present study was designed to investigate the effect of Repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride [(-)U-50,488H] on antinociception and G-protein activation induced by mu-opioid receptor agonists in mice. A single s.c. injection of (-)U-50,488H produced a dose-dependent antinociception, and this effect was reversed by a selective kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI). Furthermore, a single s.c. pre-treatment with (-)U-50,488H had no effect on the mu-opioid receptor agonist-induced antinociception. In contrast, Repeated s.c. administration of (-)U-50,488H resulted in the development of tolerance to (-)U-50,488H-induced antinociception. Under these conditions, we demonstrated here that Repeated s.c. injection of (-)U-50,488H significantly enhanced the antinociceptive effect of selective mu-opioid receptor agonists endomorphin-1, endomorphin-2 and [d-Ala2,N-MePhe4,Gly-ol5] enkephalin (DAMGO). Using the guanosine-5'-o-(3-[35S]thio) triphosphate ([35S]GTP gamma S) binding assay, we found that (-)U-50,488H was able to produce a nor-BNI-reversible increase in [35S]GTP gamma S binding to membranes of the mouse thalamus, which has a high level of kappa-opioid receptors. Repeated administration of (-)U-50,488H caused a significant reduction in the (-)U-50,488H-stimulated [35S]GTP gamma S binding in this region, whereas chronic treatment with (-)U-50,488H exhibited the increase in the endomorphin-1-, endomorphin-2- and DAMGO-stimulated [35S]GTP gamma S bindings in membranes of the thalamus and periaqueductal gray. These results suggest that Repeated Stimulation of kappa-opioid receptors leads to the heterologous up-regulation of mu-opioid receptor functions in the thalamus and periaqueductal gray regions, which may be associated with the supersensitivity of mu-opioid receptor-mediated antinociception.
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Direct evidence for the up‐regulation of spinal µ‐opioid receptor function after Repeated Stimulation of κ‐opioid receptors in the mouse
The European journal of neuroscience, 2003Co-Authors: Minoru Narita, Yoshinori Yajima, Masami Suzuki, Junaidi Khotib, Satoru Ozaki, Hirokazu Mizoguchi, Leon F. Tseng, Tsutomu SuzukiAbstract:The present study was designed to investigate the possible change in spinal micro -opioid receptor function after Repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]-benzeneacetamide hydrochloride [(-)U-50,488H] in the ICR mouse. A single s.c. or i.t. injection of (-)U-50,488H produced a dose-dependent antinociception. Repeated s.c. or i.t. administration of (-)U-50,488H resulted in the development of tolerance to (-)U-50,488H-induced antinociception. Under these conditions, we demonstrated here that Repeated s.c. injection of (-)U-50,488H significantly enhanced the antinociceptive effect induced by the i.t. administration of a selective micro -opioid receptor agonist [d-Ala2,N-Me-Phe4,Gly5-ol] enkephalin (DAMGO). Using the guanosine-5'-o-(3-[35S]thio) triphosphate ([35S]GTPgammaS) binding assay, we found that (-)U-50,488H was able to produce a dose-dependent increase in [35S]GTPgammaS binding to membranes of the mouse spinal cord. Repeated administration of (-)U-50,488H caused a significant reduction in the (-)U-50,488H-stimulated [35S]GTPgammaS binding in this region, whereas Repeated treatment with (-)U-50,488H exhibited an increase in the DAMGO-stimulated [35S]GTPgammaS binding in membranes of the spinal cord. Using a receptor binding assay, Repeated treatment with (-)U-50,488H significantly increased the density of [3H]DAMGO binding sites in membranes of the mouse spinal cord. In contrast, the expression of micro -opioid receptor was not affected after Repeated treatment with (-)U-50,488H. These results suggest that Repeated Stimulation of kappa-opioid receptors leads to the up-regulation of micro -opioid receptor functions in the spinal cord, which may be associated with an increase in the number of functional micro -opioid receptors in the mouse spinal cord.
Minoru Narita - One of the best experts on this subject based on the ideXlab platform.
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Functional interaction among opioid receptor types: up-regulation of μ- and δ-opioid receptor functions after Repeated Stimulation of κ-opioid receptors
Neuropharmacology, 2004Co-Authors: Junaidi Khotib, Minoru Narita, Yoshinori Yajima, Masami Suzuki, Tsutomu SuzukiAbstract:It has been widely accepted that Repeated administration of kappa-opioid receptor agonists leads to the development of antinociceptive tolerance. The present study was designed to investigate the effect of Repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride ((-)U-50,488H) on the mu- and delta-opioid receptor agonist-induced antinociception and G-protein activation in mice. The mice were injected either subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) pretreated with saline or (-)U-50,488H once a day for seven consecutive days. Two hours after the last injection, the mice were challenged by either mu- or delta-opioid receptor agonist for the antinociceptive assay. Repeated treatment with (-)U-50,488H (s.c. or i.c.v.) significantly enhanced antinociceptive effect of both mu-opioid receptor agonist (morphine) and delta-opioid receptor agonists ([d-Ala2]deltorphin (DELT) and (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dime thyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80) compared to saline-treated groups. Under these conditions, Repeated s.c. injection of (-)U-50,488H significantly enhanced both mu- and delta-opioid receptor agonist-stimulated [35S]GTPgammaS binding in the membrane of the thalamus. On the contrary, either Repeated administration of morphine (s.c. or i.c.v.) or SNC-80 failed to affect the kappa-opioid receptor agonist-induced antinociception and G-protein activation. Taken together, these results suggest that Repeated Stimulation of kappa-opioid receptor markedly increases the functional mu- and delta-opioid receptors, whereas Repeated Stimulation of either mu- or delta-opioid receptor had no direct effect on kappa-opioidergic function in mice.
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Functional interaction among opioid receptor types: up-regulation of μ- and δ-opioid receptor functions after Repeated Stimulation of κ-opioid receptors
Neuropharmacology, 2004Co-Authors: Junaidi Khotib, Minoru Narita, Yoshinori Yajima, Masami Suzuki, Tsutomu SuzukiAbstract:It has been widely accepted that Repeated administration of kappa-opioid receptor agonists leads to the development of antinociceptive tolerance. The present study was designed to investigate the effect of Repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride ((-)U-50,488H) on the mu- and delta-opioid receptor agonist-induced antinociception and G-protein activation in mice. The mice were injected either subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) pretreated with saline or (-)U-50,488H once a day for seven consecutive days. Two hours after the last injection, the mice were challenged by either mu- or delta-opioid receptor agonist for the antinociceptive assay. Repeated treatment with (-)U-50,488H (s.c. or i.c.v.) significantly enhanced antinociceptive effect of both mu-opioid receptor agonist (morphine) and delta-opioid receptor agonists ([d-Ala2]deltorphin (DELT) and (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dime thyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80) compared to saline-treated groups. Under these conditions, Repeated s.c. injection of (-)U-50,488H significantly enhanced both mu- and delta-opioid receptor agonist-stimulated [35S]GTPgammaS binding in the membrane of the thalamus. On the contrary, either Repeated administration of morphine (s.c. or i.c.v.) or SNC-80 failed to affect the kappa-opioid receptor agonist-induced antinociception and G-protein activation. Taken together, these results suggest that Repeated Stimulation of kappa-opioid receptor markedly increases the functional mu- and delta-opioid receptors, whereas Repeated Stimulation of either mu- or delta-opioid receptor had no direct effect on kappa-opioidergic function in mice.
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Heterologous mu-opioid receptor adaptation by Repeated Stimulation of kappa-opioid receptor: up-regulation of G-protein activation and antinociception.
Journal of neurochemistry, 2003Co-Authors: Minoru Narita, Yoshinori Yajima, Masami Suzuki, Junaidi Khotib, Satoru Ozaki, Tsutomu SuzukiAbstract:The present study was designed to investigate the effect of Repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride [(-)U-50,488H] on antinociception and G-protein activation induced by mu-opioid receptor agonists in mice. A single s.c. injection of (-)U-50,488H produced a dose-dependent antinociception, and this effect was reversed by a selective kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI). Furthermore, a single s.c. pre-treatment with (-)U-50,488H had no effect on the mu-opioid receptor agonist-induced antinociception. In contrast, Repeated s.c. administration of (-)U-50,488H resulted in the development of tolerance to (-)U-50,488H-induced antinociception. Under these conditions, we demonstrated here that Repeated s.c. injection of (-)U-50,488H significantly enhanced the antinociceptive effect of selective mu-opioid receptor agonists endomorphin-1, endomorphin-2 and [d-Ala2,N-MePhe4,Gly-ol5] enkephalin (DAMGO). Using the guanosine-5'-o-(3-[35S]thio) triphosphate ([35S]GTP gamma S) binding assay, we found that (-)U-50,488H was able to produce a nor-BNI-reversible increase in [35S]GTP gamma S binding to membranes of the mouse thalamus, which has a high level of kappa-opioid receptors. Repeated administration of (-)U-50,488H caused a significant reduction in the (-)U-50,488H-stimulated [35S]GTP gamma S binding in this region, whereas chronic treatment with (-)U-50,488H exhibited the increase in the endomorphin-1-, endomorphin-2- and DAMGO-stimulated [35S]GTP gamma S bindings in membranes of the thalamus and periaqueductal gray. These results suggest that Repeated Stimulation of kappa-opioid receptors leads to the heterologous up-regulation of mu-opioid receptor functions in the thalamus and periaqueductal gray regions, which may be associated with the supersensitivity of mu-opioid receptor-mediated antinociception.
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Direct evidence for the up‐regulation of spinal µ‐opioid receptor function after Repeated Stimulation of κ‐opioid receptors in the mouse
The European journal of neuroscience, 2003Co-Authors: Minoru Narita, Yoshinori Yajima, Masami Suzuki, Junaidi Khotib, Satoru Ozaki, Hirokazu Mizoguchi, Leon F. Tseng, Tsutomu SuzukiAbstract:The present study was designed to investigate the possible change in spinal micro -opioid receptor function after Repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]-benzeneacetamide hydrochloride [(-)U-50,488H] in the ICR mouse. A single s.c. or i.t. injection of (-)U-50,488H produced a dose-dependent antinociception. Repeated s.c. or i.t. administration of (-)U-50,488H resulted in the development of tolerance to (-)U-50,488H-induced antinociception. Under these conditions, we demonstrated here that Repeated s.c. injection of (-)U-50,488H significantly enhanced the antinociceptive effect induced by the i.t. administration of a selective micro -opioid receptor agonist [d-Ala2,N-Me-Phe4,Gly5-ol] enkephalin (DAMGO). Using the guanosine-5'-o-(3-[35S]thio) triphosphate ([35S]GTPgammaS) binding assay, we found that (-)U-50,488H was able to produce a dose-dependent increase in [35S]GTPgammaS binding to membranes of the mouse spinal cord. Repeated administration of (-)U-50,488H caused a significant reduction in the (-)U-50,488H-stimulated [35S]GTPgammaS binding in this region, whereas Repeated treatment with (-)U-50,488H exhibited an increase in the DAMGO-stimulated [35S]GTPgammaS binding in membranes of the spinal cord. Using a receptor binding assay, Repeated treatment with (-)U-50,488H significantly increased the density of [3H]DAMGO binding sites in membranes of the mouse spinal cord. In contrast, the expression of micro -opioid receptor was not affected after Repeated treatment with (-)U-50,488H. These results suggest that Repeated Stimulation of kappa-opioid receptors leads to the up-regulation of micro -opioid receptor functions in the spinal cord, which may be associated with an increase in the number of functional micro -opioid receptors in the mouse spinal cord.