Eintrag weiter verarbeiten
Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system
Gespeichert in:
Zeitschriftentitel: | British Journal of Pharmacology |
---|---|
Personen und Körperschaften: | , , , , , , |
In: | British Journal of Pharmacology, 140, 2003, 1, S. 61-70 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
Wiley
|
Schlagwörter: |
author_facet |
McDonald, J Barnes, T A Okawa, H Williams, J Calo', G Rowbotham, D J Lambert, D G McDonald, J Barnes, T A Okawa, H Williams, J Calo', G Rowbotham, D J Lambert, D G |
---|---|
author |
McDonald, J Barnes, T A Okawa, H Williams, J Calo', G Rowbotham, D J Lambert, D G |
spellingShingle |
McDonald, J Barnes, T A Okawa, H Williams, J Calo', G Rowbotham, D J Lambert, D G British Journal of Pharmacology Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system Pharmacology |
author_sort |
mcdonald, j |
spelling |
McDonald, J Barnes, T A Okawa, H Williams, J Calo', G Rowbotham, D J Lambert, D G 0007-1188 1476-5381 Wiley Pharmacology http://dx.doi.org/10.1038/sj.bjp.0705401 <jats:p> <jats:list list-type="explicit-label"> <jats:list-item><jats:p>Partial agonism is primarily dependent upon receptor density and coupling efficiency. As these parameters are tissue/model dependent, intrinsic activity in different tissues can vary. We have utilised the ecdysone‐inducible expression system containing the human nociceptin/orphanin FQ (N/OFQ) peptide receptor (hNOP) expressed in Chinese hamster ovary cells (CHO<jats:sub>INDhNOP</jats:sub>) to examine the activity of a range of partial agonists in receptor binding, GTP<jats:italic>γ</jats:italic><jats:sup>35</jats:sup>S binding and inhibition of adenylyl cyclase studies.</jats:p></jats:list-item> <jats:list-item><jats:p>Incubation of CHO<jats:sub>INDhNOP</jats:sub> cells with ponasterone A (PON) induced hNOP expression ([leucyl‐<jats:sup>3</jats:sup>H]N/OFQ binding) of 24, 68, 191 and 1101 fmol mg<jats:sup>−1</jats:sup> protein at 1, 2, 5 and 10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON, respectively. At 191 fmol mg<jats:sup>−1</jats:sup>, protein hNOP pharmacology was identical to that reported for other traditional expression systems.</jats:p></jats:list-item> <jats:list-item><jats:p>pEC<jats:sub>50</jats:sub> values for GTP<jats:italic>γ</jats:italic><jats:sup>35</jats:sup>S binding ranged from 7.23 to 7.72 (2–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for the partial agonist [Phe<jats:sup>1</jats:sup><jats:italic>ψ</jats:italic>(CH<jats:sub>2</jats:sub>–NH)Gly<jats:sup>2</jats:sup>]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> ([F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub>) and 8.12–8.60 (1–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and <jats:italic>E</jats:italic><jats:sub>max</jats:sub> values (stimulation factor relative to basal) ranged from 1.51 to 3.21 (2–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and 1.28–6.95 (1–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc>) for N/OFQ(1–13)–NH<jats:sub>2</jats:sub>. Intrinsic activity of [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> relative to N/OFQ(1–13)–NH<jats:sub>2</jats:sub> was 0.3–0.5. [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> did not stimulate GTP<jats:italic>γ</jats:italic><jats:sup>35</jats:sup>S binding at 1 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON, but competitively antagonised the effects of N/OFQ(1–13)–NH<jats:sub>2</jats:sub> with a p<jats:italic>K</jats:italic><jats:sub>B</jats:sub>=7.62.</jats:p></jats:list-item> <jats:list-item><jats:p>pEC<jats:sub>50</jats:sub> values for cAMP inhibition ranged from 8.26 to 8.32 (2–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and 9.42–10.35 for N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and <jats:italic>E</jats:italic><jats:sub>max</jats:sub> values (% inhibition) ranged from 19.6 to 83.2 for [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and 40.9–86.0 for N/OFQ(1–13)–NH<jats:sub>2</jats:sub>. The intrinsic activity of [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> relative to N/OFQ(1–13)–NH<jats:sub>2</jats:sub> was 0.48–0.97.</jats:p></jats:list-item> <jats:list-item><jats:p>In the same cellular environment with receptor density as the only variable, we show that the profile of [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> can be manipulated to encompass full and partial agonism along with antagonism.</jats:p></jats:list-item> </jats:list> </jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (2003) <jats:bold>140</jats:bold>, 61–70. doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0705401">10.1038/sj.bjp.0705401</jats:ext-link></jats:p> Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system British Journal of Pharmacology |
doi_str_mv |
10.1038/sj.bjp.0705401 |
facet_avail |
Online Free |
finc_class_facet |
Chemie und Pharmazie |
format |
ElectronicArticle |
fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTAzOC9zai5ianAuMDcwNTQwMQ |
id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTAzOC9zai5ianAuMDcwNTQwMQ |
institution |
DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 |
imprint |
Wiley, 2003 |
imprint_str_mv |
Wiley, 2003 |
issn |
0007-1188 1476-5381 |
issn_str_mv |
0007-1188 1476-5381 |
language |
English |
mega_collection |
Wiley (CrossRef) |
match_str |
mcdonald2003partialagonistbehaviourdependsuponthelevelofnociceptinorphaninfqreceptorexpressionstudiesusingtheecdysoneinduciblemammalianexpressionsystem |
publishDateSort |
2003 |
publisher |
Wiley |
recordtype |
ai |
record_format |
ai |
series |
British Journal of Pharmacology |
source_id |
49 |
title |
Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system |
title_unstemmed |
Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system |
title_full |
Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system |
title_fullStr |
Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system |
title_full_unstemmed |
Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system |
title_short |
Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system |
title_sort |
partial agonist behaviour depends upon the level of nociceptin/orphanin fq receptor expression: studies using the ecdysone‐inducible mammalian expression system |
topic |
Pharmacology |
url |
http://dx.doi.org/10.1038/sj.bjp.0705401 |
publishDate |
2003 |
physical |
61-70 |
description |
<jats:p>
<jats:list list-type="explicit-label">
<jats:list-item><jats:p>Partial agonism is primarily dependent upon receptor density and coupling efficiency. As these parameters are tissue/model dependent, intrinsic activity in different tissues can vary. We have utilised the ecdysone‐inducible expression system containing the human nociceptin/orphanin FQ (N/OFQ) peptide receptor (hNOP) expressed in Chinese hamster ovary cells (CHO<jats:sub>INDhNOP</jats:sub>) to examine the activity of a range of partial agonists in receptor binding, GTP<jats:italic>γ</jats:italic><jats:sup>35</jats:sup>S binding and inhibition of adenylyl cyclase studies.</jats:p></jats:list-item>
<jats:list-item><jats:p>Incubation of CHO<jats:sub>INDhNOP</jats:sub> cells with ponasterone A (PON) induced hNOP expression ([leucyl‐<jats:sup>3</jats:sup>H]N/OFQ binding) of 24, 68, 191 and 1101 fmol mg<jats:sup>−1</jats:sup> protein at 1, 2, 5 and 10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON, respectively. At 191 fmol mg<jats:sup>−1</jats:sup>, protein hNOP pharmacology was identical to that reported for other traditional expression systems.</jats:p></jats:list-item>
<jats:list-item><jats:p>pEC<jats:sub>50</jats:sub> values for GTP<jats:italic>γ</jats:italic><jats:sup>35</jats:sup>S binding ranged from 7.23 to 7.72 (2–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for the partial agonist [Phe<jats:sup>1</jats:sup><jats:italic>ψ</jats:italic>(CH<jats:sub>2</jats:sub>–NH)Gly<jats:sup>2</jats:sup>]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> ([F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub>) and 8.12–8.60 (1–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and <jats:italic>E</jats:italic><jats:sub>max</jats:sub> values (stimulation factor relative to basal) ranged from 1.51 to 3.21 (2–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and 1.28–6.95 (1–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc>) for N/OFQ(1–13)–NH<jats:sub>2</jats:sub>. Intrinsic activity of [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> relative to N/OFQ(1–13)–NH<jats:sub>2</jats:sub> was 0.3–0.5. [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> did not stimulate GTP<jats:italic>γ</jats:italic><jats:sup>35</jats:sup>S binding at 1 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON, but competitively antagonised the effects of N/OFQ(1–13)–NH<jats:sub>2</jats:sub> with a p<jats:italic>K</jats:italic><jats:sub>B</jats:sub>=7.62.</jats:p></jats:list-item>
<jats:list-item><jats:p>pEC<jats:sub>50</jats:sub> values for cAMP inhibition ranged from 8.26 to 8.32 (2–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and 9.42–10.35 for N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and <jats:italic>E</jats:italic><jats:sub>max</jats:sub> values (% inhibition) ranged from 19.6 to 83.2 for [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and 40.9–86.0 for N/OFQ(1–13)–NH<jats:sub>2</jats:sub>. The intrinsic activity of [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> relative to N/OFQ(1–13)–NH<jats:sub>2</jats:sub> was 0.48–0.97.</jats:p></jats:list-item>
<jats:list-item><jats:p>In the same cellular environment with receptor density as the only variable, we show that the profile of [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> can be manipulated to encompass full and partial agonism along with antagonism.</jats:p></jats:list-item>
</jats:list>
</jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (2003) <jats:bold>140</jats:bold>, 61–70. doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0705401">10.1038/sj.bjp.0705401</jats:ext-link></jats:p> |
container_issue |
1 |
container_start_page |
61 |
container_title |
British Journal of Pharmacology |
container_volume |
140 |
format_de105 |
Article, E-Article |
format_de14 |
Article, E-Article |
format_de15 |
Article, E-Article |
format_de520 |
Article, E-Article |
format_de540 |
Article, E-Article |
format_dech1 |
Article, E-Article |
format_ded117 |
Article, E-Article |
format_degla1 |
E-Article |
format_del152 |
Buch |
format_del189 |
Article, E-Article |
format_dezi4 |
Article |
format_dezwi2 |
Article, E-Article |
format_finc |
Article, E-Article |
format_nrw |
Article, E-Article |
_version_ |
1792344041167257616 |
geogr_code |
not assigned |
last_indexed |
2024-03-01T17:01:14.811Z |
geogr_code_person |
not assigned |
openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Partial+agonist+behaviour+depends+upon+the+level+of+nociceptin%2Forphanin+FQ+receptor+expression%3A+studies+using+the+ecdysone%E2%80%90inducible+mammalian+expression+system&rft.date=2003-09-01&genre=article&issn=1476-5381&volume=140&issue=1&spage=61&epage=70&pages=61-70&jtitle=British+Journal+of+Pharmacology&atitle=Partial+agonist+behaviour+depends+upon+the+level+of+nociceptin%2Forphanin+FQ+receptor+expression%3A+studies+using+the+ecdysone%E2%80%90inducible+mammalian+expression+system&aulast=Lambert&aufirst=D+G&rft_id=info%3Adoi%2F10.1038%2Fsj.bjp.0705401&rft.language%5B0%5D=eng |
SOLR | |
_version_ | 1792344041167257616 |
author | McDonald, J, Barnes, T A, Okawa, H, Williams, J, Calo', G, Rowbotham, D J, Lambert, D G |
author_facet | McDonald, J, Barnes, T A, Okawa, H, Williams, J, Calo', G, Rowbotham, D J, Lambert, D G, McDonald, J, Barnes, T A, Okawa, H, Williams, J, Calo', G, Rowbotham, D J, Lambert, D G |
author_sort | mcdonald, j |
container_issue | 1 |
container_start_page | 61 |
container_title | British Journal of Pharmacology |
container_volume | 140 |
description | <jats:p> <jats:list list-type="explicit-label"> <jats:list-item><jats:p>Partial agonism is primarily dependent upon receptor density and coupling efficiency. As these parameters are tissue/model dependent, intrinsic activity in different tissues can vary. We have utilised the ecdysone‐inducible expression system containing the human nociceptin/orphanin FQ (N/OFQ) peptide receptor (hNOP) expressed in Chinese hamster ovary cells (CHO<jats:sub>INDhNOP</jats:sub>) to examine the activity of a range of partial agonists in receptor binding, GTP<jats:italic>γ</jats:italic><jats:sup>35</jats:sup>S binding and inhibition of adenylyl cyclase studies.</jats:p></jats:list-item> <jats:list-item><jats:p>Incubation of CHO<jats:sub>INDhNOP</jats:sub> cells with ponasterone A (PON) induced hNOP expression ([leucyl‐<jats:sup>3</jats:sup>H]N/OFQ binding) of 24, 68, 191 and 1101 fmol mg<jats:sup>−1</jats:sup> protein at 1, 2, 5 and 10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON, respectively. At 191 fmol mg<jats:sup>−1</jats:sup>, protein hNOP pharmacology was identical to that reported for other traditional expression systems.</jats:p></jats:list-item> <jats:list-item><jats:p>pEC<jats:sub>50</jats:sub> values for GTP<jats:italic>γ</jats:italic><jats:sup>35</jats:sup>S binding ranged from 7.23 to 7.72 (2–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for the partial agonist [Phe<jats:sup>1</jats:sup><jats:italic>ψ</jats:italic>(CH<jats:sub>2</jats:sub>–NH)Gly<jats:sup>2</jats:sup>]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> ([F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub>) and 8.12–8.60 (1–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and <jats:italic>E</jats:italic><jats:sub>max</jats:sub> values (stimulation factor relative to basal) ranged from 1.51 to 3.21 (2–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and 1.28–6.95 (1–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc>) for N/OFQ(1–13)–NH<jats:sub>2</jats:sub>. Intrinsic activity of [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> relative to N/OFQ(1–13)–NH<jats:sub>2</jats:sub> was 0.3–0.5. [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> did not stimulate GTP<jats:italic>γ</jats:italic><jats:sup>35</jats:sup>S binding at 1 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON, but competitively antagonised the effects of N/OFQ(1–13)–NH<jats:sub>2</jats:sub> with a p<jats:italic>K</jats:italic><jats:sub>B</jats:sub>=7.62.</jats:p></jats:list-item> <jats:list-item><jats:p>pEC<jats:sub>50</jats:sub> values for cAMP inhibition ranged from 8.26 to 8.32 (2–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and 9.42–10.35 for N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and <jats:italic>E</jats:italic><jats:sub>max</jats:sub> values (% inhibition) ranged from 19.6 to 83.2 for [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and 40.9–86.0 for N/OFQ(1–13)–NH<jats:sub>2</jats:sub>. The intrinsic activity of [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> relative to N/OFQ(1–13)–NH<jats:sub>2</jats:sub> was 0.48–0.97.</jats:p></jats:list-item> <jats:list-item><jats:p>In the same cellular environment with receptor density as the only variable, we show that the profile of [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> can be manipulated to encompass full and partial agonism along with antagonism.</jats:p></jats:list-item> </jats:list> </jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (2003) <jats:bold>140</jats:bold>, 61–70. doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0705401">10.1038/sj.bjp.0705401</jats:ext-link></jats:p> |
doi_str_mv | 10.1038/sj.bjp.0705401 |
facet_avail | Online, Free |
finc_class_facet | Chemie und Pharmazie |
format | ElectronicArticle |
format_de105 | Article, E-Article |
format_de14 | Article, E-Article |
format_de15 | Article, E-Article |
format_de520 | Article, E-Article |
format_de540 | Article, E-Article |
format_dech1 | Article, E-Article |
format_ded117 | Article, E-Article |
format_degla1 | E-Article |
format_del152 | Buch |
format_del189 | Article, E-Article |
format_dezi4 | Article |
format_dezwi2 | Article, E-Article |
format_finc | Article, E-Article |
format_nrw | Article, E-Article |
geogr_code | not assigned |
geogr_code_person | not assigned |
id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTAzOC9zai5ianAuMDcwNTQwMQ |
imprint | Wiley, 2003 |
imprint_str_mv | Wiley, 2003 |
institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
issn | 0007-1188, 1476-5381 |
issn_str_mv | 0007-1188, 1476-5381 |
language | English |
last_indexed | 2024-03-01T17:01:14.811Z |
match_str | mcdonald2003partialagonistbehaviourdependsuponthelevelofnociceptinorphaninfqreceptorexpressionstudiesusingtheecdysoneinduciblemammalianexpressionsystem |
mega_collection | Wiley (CrossRef) |
physical | 61-70 |
publishDate | 2003 |
publishDateSort | 2003 |
publisher | Wiley |
record_format | ai |
recordtype | ai |
series | British Journal of Pharmacology |
source_id | 49 |
spelling | McDonald, J Barnes, T A Okawa, H Williams, J Calo', G Rowbotham, D J Lambert, D G 0007-1188 1476-5381 Wiley Pharmacology http://dx.doi.org/10.1038/sj.bjp.0705401 <jats:p> <jats:list list-type="explicit-label"> <jats:list-item><jats:p>Partial agonism is primarily dependent upon receptor density and coupling efficiency. As these parameters are tissue/model dependent, intrinsic activity in different tissues can vary. We have utilised the ecdysone‐inducible expression system containing the human nociceptin/orphanin FQ (N/OFQ) peptide receptor (hNOP) expressed in Chinese hamster ovary cells (CHO<jats:sub>INDhNOP</jats:sub>) to examine the activity of a range of partial agonists in receptor binding, GTP<jats:italic>γ</jats:italic><jats:sup>35</jats:sup>S binding and inhibition of adenylyl cyclase studies.</jats:p></jats:list-item> <jats:list-item><jats:p>Incubation of CHO<jats:sub>INDhNOP</jats:sub> cells with ponasterone A (PON) induced hNOP expression ([leucyl‐<jats:sup>3</jats:sup>H]N/OFQ binding) of 24, 68, 191 and 1101 fmol mg<jats:sup>−1</jats:sup> protein at 1, 2, 5 and 10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON, respectively. At 191 fmol mg<jats:sup>−1</jats:sup>, protein hNOP pharmacology was identical to that reported for other traditional expression systems.</jats:p></jats:list-item> <jats:list-item><jats:p>pEC<jats:sub>50</jats:sub> values for GTP<jats:italic>γ</jats:italic><jats:sup>35</jats:sup>S binding ranged from 7.23 to 7.72 (2–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for the partial agonist [Phe<jats:sup>1</jats:sup><jats:italic>ψ</jats:italic>(CH<jats:sub>2</jats:sub>–NH)Gly<jats:sup>2</jats:sup>]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> ([F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub>) and 8.12–8.60 (1–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and <jats:italic>E</jats:italic><jats:sub>max</jats:sub> values (stimulation factor relative to basal) ranged from 1.51 to 3.21 (2–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and 1.28–6.95 (1–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc>) for N/OFQ(1–13)–NH<jats:sub>2</jats:sub>. Intrinsic activity of [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> relative to N/OFQ(1–13)–NH<jats:sub>2</jats:sub> was 0.3–0.5. [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> did not stimulate GTP<jats:italic>γ</jats:italic><jats:sup>35</jats:sup>S binding at 1 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON, but competitively antagonised the effects of N/OFQ(1–13)–NH<jats:sub>2</jats:sub> with a p<jats:italic>K</jats:italic><jats:sub>B</jats:sub>=7.62.</jats:p></jats:list-item> <jats:list-item><jats:p>pEC<jats:sub>50</jats:sub> values for cAMP inhibition ranged from 8.26 to 8.32 (2–10 <jats:italic>μ</jats:italic><jats:sc>M</jats:sc> PON) for [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and 9.42–10.35 for N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and <jats:italic>E</jats:italic><jats:sub>max</jats:sub> values (% inhibition) ranged from 19.6 to 83.2 for [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> and 40.9–86.0 for N/OFQ(1–13)–NH<jats:sub>2</jats:sub>. The intrinsic activity of [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> relative to N/OFQ(1–13)–NH<jats:sub>2</jats:sub> was 0.48–0.97.</jats:p></jats:list-item> <jats:list-item><jats:p>In the same cellular environment with receptor density as the only variable, we show that the profile of [F/G]N/OFQ(1–13)–NH<jats:sub>2</jats:sub> can be manipulated to encompass full and partial agonism along with antagonism.</jats:p></jats:list-item> </jats:list> </jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (2003) <jats:bold>140</jats:bold>, 61–70. doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0705401">10.1038/sj.bjp.0705401</jats:ext-link></jats:p> Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system British Journal of Pharmacology |
spellingShingle | McDonald, J, Barnes, T A, Okawa, H, Williams, J, Calo', G, Rowbotham, D J, Lambert, D G, British Journal of Pharmacology, Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system, Pharmacology |
title | Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system |
title_full | Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system |
title_fullStr | Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system |
title_full_unstemmed | Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system |
title_short | Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system |
title_sort | partial agonist behaviour depends upon the level of nociceptin/orphanin fq receptor expression: studies using the ecdysone‐inducible mammalian expression system |
title_unstemmed | Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone‐inducible mammalian expression system |
topic | Pharmacology |
url | http://dx.doi.org/10.1038/sj.bjp.0705401 |