ArticleNaunyn-Schmiedeberg's archives of pharmacology2005
Novel human alpha1a-adrenoceptor single nucleotide polymorphisms alter receptor pharmacology and biological function.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The trial behind it
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
21 citing papers in PubMed, 35 citations in OpenAlex.
- The α-1 adrenoceptor (ADRA1A) genotype moderates the magnitude of acute cocaine-induced subjective effects in cocaine-dependent individuals.Pharmacogenetics and genomics · 2016Trial
- Pharmacogenetic randomized trial for cocaine abuse: disulfiram and α1A-adrenoceptor gene variation.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2013Trial
- Vascular Reactions of the Diving Reflex in Men and Women Carrying Different ADRA1A Genotypes.International journal of molecular sciences · 2022Article
- Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma Patients.Biomedicines · 2022Article
- Adrenergic receptors gene polymorphisms and autonomic nervous control of heart and vascular tone.Physiological research · 2021Review
- Differentiation of rodent behavioral phenotypes and methylphenidate action in sustained and flexible attention tasks.Brain research · 2016Article
- A review of pharmacogenetic studies of substance-related disorders.Drug and alcohol dependence · 2015Review
- Article
- Temporal Dissection of Rate Limiting Transcriptional Events Using Pol II ChIP and RNA Analysis of Adrenergic Stress Gene Activation.PloS one · 2015Article
- Alpha1a-adrenoceptor genetic variant induces cardiomyoblast-to-fibroblast-like cell transition via distinct signaling pathways.Cellular signalling · 2014Article
- Large-scale polymorphism discovery in macaque G-protein coupled receptors.BMC genomics · 2013Article
- Article
- Constitutive coupling of a naturally occurring human alpha1a-adrenergic receptor genetic variant to EGFR transactivation pathway.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- RAAS and adrenergic genes in heart failure: Function, predisposition and survival implications.World journal of cardiology · 2010Article
- ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics.The pharmacogenomics journal · 2010Article
- Subtypes of alpha1-adrenoceptors in BPH: future prospects for personalized medicine.Nature clinical practice. Urology · 2009Review
- Association of alpha1a-adrenergic receptor polymorphism and blood pressure phenotypes in the Brazilian population.BMC cardiovascular disorders · 2008Article
- The alpha1a-adrenergic receptor occupies membrane rafts with its G protein effectors but internalizes via clathrin-coated pits.The Journal of biological chemistry · 2008Article
- Piloerection induced by replacing fluvoxamine with milnacipran.British journal of clinical pharmacology · 2007Article
- Impact of GPCRs in clinical medicine: monogenic diseases, genetic variants and drug targets.Biochimica et biophysica acta · 2007Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
We identified nine naturally-occurring human single nucleotide polymorphisms (SNPs) in the alpha(1a)-adrenoceptor (alpha(1a)AR) coding region, seven of which result in amino acid change. Utilizing rat-1 fibroblasts stably expressing wild type alpha(1a)AR or each SNP at both high and low levels, we investigated the effect of these SNPs on receptor function. Compared with wild type, two SNPs (R166K, V311I) cause a decrease in binding affinity for agonists norepinephrine, epinephrine, and phenylephrine, and also shift the dose-response curve for norepinephrine stimulation of inositol phosphate (IP) production to the right (reduced potency) without altering maximal IP activity. In addition, SNP V311I and I200S display altered antagonist binding. Interestingly, a receptor with SNP G247R (located in the third intracellular loop) displays increased maximal receptor IP activity and stimulates cell growth. The increased receptor signaling for alpha(1a)AR G247R is not mediated by altered ligand binding or a deficiency in agonist-mediated desensitization, but appears to be related to enhanced receptor-G protein coupling. In conclusion, four naturally-occurring human alpha(1a)AR SNPs induce altered receptor pharmacology and/or biological activity. This finding has potentially important implications in many areas of medicine and can be used to guide alpha(1a)AR SNP choice for future clinical studies.
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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.