Inverse agonism at G protein-coupled receptors: (patho)physiological relevance and implications for drug discovery

doi:10.1038/sj.bjp.0703311

Review

. 2000 May;130(1):1-12.

doi: 10.1038/sj.bjp.0703311.

Inverse agonism at G protein-coupled receptors: (patho)physiological relevance and implications for drug discovery

R A de Ligt¹, A P Kourounakis, A P IJzerman

Affiliations

PMID: 10780991
PMCID: PMC1572052
DOI: 10.1038/sj.bjp.0703311

Review

Inverse agonism at G protein-coupled receptors: (patho)physiological relevance and implications for drug discovery

R A de Ligt et al. Br J Pharmacol. 2000 May.

. 2000 May;130(1):1-12.

doi: 10.1038/sj.bjp.0703311.

Authors

R A de Ligt¹, A P Kourounakis, A P IJzerman

Affiliation

¹ Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry, PO Box 9502, 2300RA Leiden, The Netherlands.

PMID: 10780991
PMCID: PMC1572052
DOI: 10.1038/sj.bjp.0703311

No abstract available

PubMed Disclaimer

Figures

**Figure 1**
Atropine behaves as an inverse agonist on calcium currents (I_Ca) in frog ventricular cells (reproduced with permission from Hanf *et al*., 1993).

**Figure 2**
Simplified model representing the two conformational states of a receptor (inactive R, and active R^*) and their differential affinities for ligands.

See this image and copyright information in PMC

Cited by

Phasic and Tonic mGlu7 Receptor Activity Modulates the Thalamocortical Network.
Tassin V, Girard B, Chotte A, Fontanaud P, Rigault D, Kalinichev M, Perroy J, Acher F, Fagni L, Bertaso F. Tassin V, et al. Front Neural Circuits. 2016 Apr 25;10:31. doi: 10.3389/fncir.2016.00031. eCollection 2016. Front Neural Circuits. 2016. PMID: 27199672 Free PMC article.
Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G-protein-coupled receptors.
Hermans E, Challiss RA. Hermans E, et al. Biochem J. 2001 Nov 1;359(Pt 3):465-84. doi: 10.1042/0264-6021:3590465. Biochem J. 2001. PMID: 11672421 Free PMC article. Review.
Characterization of human and rodent native and recombinant adenosine A(2B) receptors by radioligand binding studies.
Bertarelli DC, Diekmann M, Hayallah AM, Rüsing D, Iqbal J, Preiss B, Verspohl EJ, Müller CE. Bertarelli DC, et al. Purinergic Signal. 2006 Sep;2(3):559-71. doi: 10.1007/s11302-006-9012-4. Epub 2006 Jul 8. Purinergic Signal. 2006. PMID: 18404493 Free PMC article.
Novel Molecular Mechanism of Lenalidomide in Myeloid Malignancies Independent of Deletion of Chromosome 5q.
Park I, Phan TM, Fang J. Park I, et al. Cancers (Basel). 2021 Oct 11;13(20):5084. doi: 10.3390/cancers13205084. Cancers (Basel). 2021. PMID: 34680233 Free PMC article. Review.
2-Phenylimidazo[2,1-i]purin-5-ones: structure-activity relationships and characterization of potent and selective inverse agonists at Human A3 adenosine receptors.
Ozola V, Thorand M, Diekmann M, Qurishi R, Schumacher B, Jacobson KA, Müller CE. Ozola V, et al. Bioorg Med Chem. 2003 Feb 6;11(3):347-56. doi: 10.1016/s0968-0896(02)00456-x. Bioorg Med Chem. 2003. PMID: 12517430 Free PMC article.

See all "Cited by" articles

References

1. ALEWIJNSE A.E., SMIT M.J., HOFFMANN M., VERZIJL D., TIMMERMAN H., LEURS R. Constitutive activity and structural instability of the wild type human H2 receptor. J. Neurochem. 1998;71:799–807. - PubMed
1. APPELMANS N., CARROLL J.A., RANCE M.J., SIMON E.J., TRAYNOR J.R. Sodium ions increase the binding of the antagonist peptide ICI 174864 to the delta opiate receptor. Neuropeptides. 1986;7:139–143. - PubMed
1. BERG K.A., STOUT B.D., CROPPER J.D., MAAYANI S., CLARKE W.P. Novel actions of inverse agonists on 5-HT2C receptor systems. Mol. Pharmacol. 1999;55:863–872. - PubMed
1. BERRIE C.P., BIRDSALL N.J., BURGEN A.S., HULME E.C. Guanine nucleotides modulate muscarinic receptor binding in the heart. Biochem. Biophys. Res. Commun. 1979;87:1000–1005. - PubMed
1. BOND R.A., LEFF P., JOHNSON T.D., MILANO C.A., ROCKMAN H.A., MCMINN T.R., APPARSUNDARAM S., HYEK M.F., KENAKIN T.P., ALLEN L.F., LEFKOWITZ R.J. Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the beta(2)-adrenoceptor. Nature. 1995;374:272–276. - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database

[1] ALEWIJNSE A.E., SMIT M.J., HOFFMANN M., VERZIJL D., TIMMERMAN H., LEURS R. Constitutive activity and structural instability of the wild type human H2 receptor. J. Neurochem. 1998;71:799–807. - PubMed

[2] ALEWIJNSE A.E., SMIT M.J., HOFFMANN M., VERZIJL D., TIMMERMAN H., LEURS R. Constitutive activity and structural instability of the wild type human H2 receptor. J. Neurochem. 1998;71:799–807. - PubMed

[3] APPELMANS N., CARROLL J.A., RANCE M.J., SIMON E.J., TRAYNOR J.R. Sodium ions increase the binding of the antagonist peptide ICI 174864 to the delta opiate receptor. Neuropeptides. 1986;7:139–143. - PubMed

[4] APPELMANS N., CARROLL J.A., RANCE M.J., SIMON E.J., TRAYNOR J.R. Sodium ions increase the binding of the antagonist peptide ICI 174864 to the delta opiate receptor. Neuropeptides. 1986;7:139–143. - PubMed

[5] BERG K.A., STOUT B.D., CROPPER J.D., MAAYANI S., CLARKE W.P. Novel actions of inverse agonists on 5-HT2C receptor systems. Mol. Pharmacol. 1999;55:863–872. - PubMed

[6] BERG K.A., STOUT B.D., CROPPER J.D., MAAYANI S., CLARKE W.P. Novel actions of inverse agonists on 5-HT2C receptor systems. Mol. Pharmacol. 1999;55:863–872. - PubMed

[7] BERRIE C.P., BIRDSALL N.J., BURGEN A.S., HULME E.C. Guanine nucleotides modulate muscarinic receptor binding in the heart. Biochem. Biophys. Res. Commun. 1979;87:1000–1005. - PubMed

[8] BERRIE C.P., BIRDSALL N.J., BURGEN A.S., HULME E.C. Guanine nucleotides modulate muscarinic receptor binding in the heart. Biochem. Biophys. Res. Commun. 1979;87:1000–1005. - PubMed

[9] BOND R.A., LEFF P., JOHNSON T.D., MILANO C.A., ROCKMAN H.A., MCMINN T.R., APPARSUNDARAM S., HYEK M.F., KENAKIN T.P., ALLEN L.F., LEFKOWITZ R.J. Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the beta(2)-adrenoceptor. Nature. 1995;374:272–276. - PubMed

[10] BOND R.A., LEFF P., JOHNSON T.D., MILANO C.A., ROCKMAN H.A., MCMINN T.R., APPARSUNDARAM S., HYEK M.F., KENAKIN T.P., ALLEN L.F., LEFKOWITZ R.J. Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the beta(2)-adrenoceptor. Nature. 1995;374:272–276. - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Inverse agonism at G protein-coupled receptors: (patho)physiological relevance and implications for drug discovery

Affiliation

Inverse agonism at G protein-coupled receptors: (patho)physiological relevance and implications for drug discovery

Authors

Affiliation

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources