ArticleBritish journal of pharmacology2000
Inverse agonism and neutral antagonism at a constitutively active alpha-1a adrenoceptor.
Article in British journal of pharmacology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Pooled it
- The Role of the Paraventricular-Coerulear Network on the Programming of Hypertension by Prenatal Undernutrition.International journal of molecular sciences · 2022Review
- Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular-Coerulear Excitatory Interactions.Molecules (Basel, Switzerland) · 2021Article
- Probing the correlation between ligand efficacy and conformational diversity at the αThe Journal of biological chemistry · 2020Article
- Evidence for altered brain reactivity to norepinephrine in Veterans with a history of traumatic stress.Neurobiology of stress · 2018Article
- BIGL: Biochemically Intuitive Generalized Loewe null model for prediction of the expected combined effect compatible with partial agonism and antagonism.Scientific reports · 2017Article
- Feedback regulation of G protein-coupled receptor signaling by GRKs and arrestins.Seminars in cell & developmental biology · 2016Review
- Update on the Mechanism of Action of Aripiprazole: Translational Insights into Antipsychotic Strategies Beyond Dopamine Receptor Antagonism.CNS drugs · 2015Review
- Novel role of mechanosensitive AT1B receptors in myogenic vasoconstriction.Pflugers Archiv : European journal of physiology · 2014Article
- alpha(1A)- and alpha(1B)-adrenergic receptors differentially modulate antidepressant-like behavior in the mouse.Brain research · 2009Article
- Alpha-1 adrenoceptor up-regulation induced by prazosin but not KMD-3213 or reserpine in rats.British journal of pharmacology · 2002Article
- Detection of receptor ligands by monitoring selective stabilization of a Renilla luciferase-tagged, constitutively active mutant, G-protein-coupled receptor.British journal of pharmacology · 2001Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have studied the antagonist action of prazosin and KMD-3213 in a constitutively active mutant of the human alpha-1a adrenoceptor in which Ala(271) was substituted to Thr and was expressed in CHO cells. Inverse agonism was characterized by up-regulation of receptor density, a decrease in basal GTPgammaS binding, and a reduction in basal inositol-1,4,5-trisphosphate (IP(3)) level. According to the above criteria, prazosin acted as an inverse agonist, whilst KMD-3213 behaved as a neutral antagonist. Compared with the wild-type receptor, mutant receptor exhibited single affinity sites for [(3)H]-prazosin, [(3)H]-KMD and the non-radioactive ligands tested, and displayed significantly higher affinities for several agonists but not for the two antagonists. Administration of KMD-3213 to prazosin-treated CHO cells expressing the mutant receptor reversed the inverse agonism of prazosin resulting in rapid increases in cellular IP(3), in intracellular [Ca(2+)] and in the rate of extracellular acidification. These results indicated that a neutral antagonist can reverse the action of an inverse agonist at the receptor site. The distinct properties of inverse agonist and neutral antagonist in affecting receptor function may be important for the clinical use of such antagonists.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.