Attenuation of opioid tolerance by ETB receptor agonist, IRL-1620, is independent of an accompanied decrease in nerve growth factor in mice
Aim: ETA receptor antagonists reverse opioid tolerance but the involvement of ETB receptors is unknown. In morphine or oxycodone tolerant mice we investigated (1) the effect of ETB receptor agonist, IRL-1620, on analgesic tolerance; (2) changes in expression of the brain ETA and ETB receptors; and (...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-06-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844016325476 |
| _version_ | 1818476437112356864 |
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| author | Shruti Gulati Seema Briyal Shantel Jones Shaifali Bhalla Anil Gulati |
| author_facet | Shruti Gulati Seema Briyal Shantel Jones Shaifali Bhalla Anil Gulati |
| author_sort | Shruti Gulati |
| collection | DOAJ |
| description | Aim: ETA receptor antagonists reverse opioid tolerance but the involvement of ETB receptors is unknown. In morphine or oxycodone tolerant mice we investigated (1) the effect of ETB receptor agonist, IRL-1620, on analgesic tolerance; (2) changes in expression of the brain ETA and ETB receptors; and (3) alterations in the brain VEGF, NGF, PI3K and notch-1 expression. Main methods: Body weight, body temperature, and tail-flick latency were assessed before and after a challenge dose of morphine or oxycodone in vehicle or IRL-1620 treated mice. Expression studies were carried out using Western blots. Key findings: Tail flick latency to a challenge dose of opioid was significantly increased by IRL-1620 from 39% to 100% in morphine tolerant and from 8% to 83% in oxycodone tolerant mice. Morphine or oxycodone did not alter ETA or ETB receptor expression. IRL-1620 had no effect on ETA however it increased (61%) expression of ETB receptors. IRL-1620-induced increase in ETB receptor expression was attenuated by morphine (39.8%) and oxycodone (51.8%). VEGF expression was not affected by morphine or oxycodone and was unaltered by IRL-1620. However, NGF and PI3K expression was decreased (P < 0.001) by morphine and oxycodone and was unaffected by IRL-1620. Notch-1 expression was not altered by morphine, oxycodone or IRL-1620. Significance: ETB receptor agonist, IRL-1620, restored analgesic tolerance to morphine and oxycodone, but it did not affect morphine and oxycodone induced decrease in NGF/PI3K expression. It is concluded that IRL-1620 attenuates opioid tolerance without the involvement of NGF/PI3K pathway. |
| first_indexed | 2024-12-10T09:25:37Z |
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| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-10T09:25:37Z |
| publishDate | 2017-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-64b4548f2ab34ecdbf8721184b17e8af2022-12-22T01:54:33ZengElsevierHeliyon2405-84402017-06-0136e00317Attenuation of opioid tolerance by ETB receptor agonist, IRL-1620, is independent of an accompanied decrease in nerve growth factor in miceShruti Gulati0Seema Briyal1Shantel Jones2Shaifali Bhalla3Anil Gulati4Chicago College of Health Sciences, Midwestern University, Downers Grove, IL 60515, USAChicago College of Pharmacy, Midwestern University, Downers Grove, IL 60515, USAChicago College of Pharmacy, Midwestern University, Downers Grove, IL 60515, USAChicago College of Pharmacy, Midwestern University, Downers Grove, IL 60515, USAChicago College of Pharmacy, Midwestern University, Downers Grove, IL 60515, USA; Corresponding author at: Chicago College of Pharmacy, Midwestern University, 555 31st Street, Downers Grove, IL 60515.Aim: ETA receptor antagonists reverse opioid tolerance but the involvement of ETB receptors is unknown. In morphine or oxycodone tolerant mice we investigated (1) the effect of ETB receptor agonist, IRL-1620, on analgesic tolerance; (2) changes in expression of the brain ETA and ETB receptors; and (3) alterations in the brain VEGF, NGF, PI3K and notch-1 expression. Main methods: Body weight, body temperature, and tail-flick latency were assessed before and after a challenge dose of morphine or oxycodone in vehicle or IRL-1620 treated mice. Expression studies were carried out using Western blots. Key findings: Tail flick latency to a challenge dose of opioid was significantly increased by IRL-1620 from 39% to 100% in morphine tolerant and from 8% to 83% in oxycodone tolerant mice. Morphine or oxycodone did not alter ETA or ETB receptor expression. IRL-1620 had no effect on ETA however it increased (61%) expression of ETB receptors. IRL-1620-induced increase in ETB receptor expression was attenuated by morphine (39.8%) and oxycodone (51.8%). VEGF expression was not affected by morphine or oxycodone and was unaltered by IRL-1620. However, NGF and PI3K expression was decreased (P < 0.001) by morphine and oxycodone and was unaffected by IRL-1620. Notch-1 expression was not altered by morphine, oxycodone or IRL-1620. Significance: ETB receptor agonist, IRL-1620, restored analgesic tolerance to morphine and oxycodone, but it did not affect morphine and oxycodone induced decrease in NGF/PI3K expression. It is concluded that IRL-1620 attenuates opioid tolerance without the involvement of NGF/PI3K pathway.http://www.sciencedirect.com/science/article/pii/S2405844016325476Neuroscience |
| spellingShingle | Shruti Gulati Seema Briyal Shantel Jones Shaifali Bhalla Anil Gulati Attenuation of opioid tolerance by ETB receptor agonist, IRL-1620, is independent of an accompanied decrease in nerve growth factor in mice Heliyon Neuroscience |
| title | Attenuation of opioid tolerance by ETB receptor agonist, IRL-1620, is independent of an accompanied decrease in nerve growth factor in mice |
| title_full | Attenuation of opioid tolerance by ETB receptor agonist, IRL-1620, is independent of an accompanied decrease in nerve growth factor in mice |
| title_fullStr | Attenuation of opioid tolerance by ETB receptor agonist, IRL-1620, is independent of an accompanied decrease in nerve growth factor in mice |
| title_full_unstemmed | Attenuation of opioid tolerance by ETB receptor agonist, IRL-1620, is independent of an accompanied decrease in nerve growth factor in mice |
| title_short | Attenuation of opioid tolerance by ETB receptor agonist, IRL-1620, is independent of an accompanied decrease in nerve growth factor in mice |
| title_sort | attenuation of opioid tolerance by etb receptor agonist irl 1620 is independent of an accompanied decrease in nerve growth factor in mice |
| topic | Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2405844016325476 |
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