Article date: February 2006
By: Maria C Olianas, Danilo Concas, Pierluigi Onali in Volume 147, Issue 4, pages 360-370
In the present study, we examined the pharmacological activity of the putative κ3‐opioid receptor agonist naloxone benzoylhydrazone (NalBzoH) at recombinant human opioid receptors individually expressed in Chinese hamster ovary (CHO) cells and native opioid receptors present in rat striatum.
At the μ‐opioid receptor (MOR), NalBzoH stimulated guanosine‐5′‐O‐(3‐[35S]thio)triphosphate ([35S]GTPγS) binding (pEC50=8.59) and inhibited cyclic AMP accumulation (pEC50=8.74) with maximal effects (Emax) corresponding to 55 and 65% of those obtained with the MOR agonist DAMGO, respectively. The MOR antagonist CTAP blocked the stimulatory effects of NalBzoH and DAMGO with similar potencies.
At the κ‐opioid receptor (KOR), NalBzoH stimulated [35S]GTPγS binding (pEC50=9.70) and inhibited cyclic AMP formation (pEC50=9.45) as effectively as the selective KOR agonist (−)‐U‐50,488. The NalBzoH effect was blocked by the KOR antagonist nor‐binaltorphimine (nor‐BNI) (pKi=10.30).
In CHO cells expressing the δ‐opioid receptor (DOR), NalBzoH increased [35S]GTPγS binding (pEC50=8.49) and inhibited cyclic AMP formation (pEC50=8.61) almost as effectively as the DOR agonist DPDPE. Naltrindole (NTI), a selective DOR antagonist, completely blocked the response to NalBzoH (pKi of 10.40).
In CHO cells expressing the nociceptin/orphanin FQ (N/OFQ) receptor (NOP), NalBzoH failed to exert agonist effects and antagonized the agonist‐induced receptor activation.
When compared to other opioid receptor ligands, NalBzoH showed an efficacy that was lower than that of morphine at MOR, but higher at KOR and DOR.
In rat striatum, NalBzoH enhanced [35S]GTPγS binding and inhibited adenylyl cyclase activity. These effects were antagonized by either CTAP, nor‐BNI or NTI, each antagonist blocking a fraction of the NalBzoH response.
These data demonstrate that NalBzoH displays agonist activity at MOR, DOR and KOR expressed either in a heterologous cell system or in a native environment.
In the present study, we examined the pharmacological activity of the putative κ3‐opioid receptor agonist naloxone benzoylhydrazone (NalBzoH) at recombinant human opioid receptors individually expressed in Chinese hamster ovary (CHO) cells and native opioid receptors present in rat striatum.
At the μ‐opioid receptor (MOR), NalBzoH stimulated guanosine‐5′‐O‐(3‐[35S]thio)triphosphate ([35S]GTPγS) binding (pEC50=8.59) and inhibited cyclic AMP accumulation (pEC50=8.74) with maximal effects (Emax) corresponding to 55 and 65% of those obtained with the MOR agonist DAMGO, respectively. The MOR antagonist CTAP blocked the stimulatory effects of NalBzoH and DAMGO with similar potencies.
At the κ‐opioid receptor (KOR), NalBzoH stimulated [35S]GTPγS binding (pEC50=9.70) and inhibited cyclic AMP formation (pEC50=9.45) as effectively as the selective KOR agonist (−)‐U‐50,488. The NalBzoH effect was blocked by the KOR antagonist nor‐binaltorphimine (nor‐BNI) (pKi=10.30).
In CHO cells expressing the δ‐opioid receptor (DOR), NalBzoH increased [35S]GTPγS binding (pEC50=8.49) and inhibited cyclic AMP formation (pEC50=8.61) almost as effectively as the DOR agonist DPDPE. Naltrindole (NTI), a selective DOR antagonist, completely blocked the response to NalBzoH (pKi of 10.40).
In CHO cells expressing the nociceptin/orphanin FQ (N/OFQ) receptor (NOP), NalBzoH failed to exert agonist effects and antagonized the agonist‐induced receptor activation.
When compared to other opioid receptor ligands, NalBzoH showed an efficacy that was lower than that of morphine at MOR, but higher at KOR and DOR.
In rat striatum, NalBzoH enhanced [35S]GTPγS binding and inhibited adenylyl cyclase activity. These effects were antagonized by either CTAP, nor‐BNI or NTI, each antagonist blocking a fraction of the NalBzoH response.
These data demonstrate that NalBzoH displays agonist activity at MOR, DOR and KOR expressed either in a heterologous cell system or in a native environment.
British Journal of Pharmacology (2006) 147, 360–370. doi:10.1038/sj.bjp.0706601
DOI: 10.1038/sj.bjp.0706601
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