{"doi":"10.1152/ajpheart.01319.2005","title":"Role of A<sub>1</sub>adenosine receptor in the regulation of coronary flow","abstract":"<jats:p>To determine whether A<jats:sub>1</jats:sub>adenosine receptors (AR) participate in adenosine-induced changes of coronary flow, isolated hearts from A<jats:sub>1</jats:sub>AR<jats:sup>−/−</jats:sup>and A<jats:sub>1</jats:sub>AR<jats:sup>+/+</jats:sup>mice were perfused under constant pressure, and the effects of nonselective and selective agonists were examined. Adenosine, 5′- N-ethylcarboxamidoadenosine (NECA, nonselective), and the selective A<jats:sub>2A</jats:sub>AR agonist 2–2-carboxyethylphenethylamino-5′- N-ethylcarboxamidoadenosine (CGS-21680) augmented maximal coronary vasodilation in A<jats:sub>1</jats:sub>AR<jats:sup>−/−</jats:sup>hearts compared with A<jats:sub>1</jats:sub>AR<jats:sup>+/+</jats:sup>hearts. Basal coronary flow was increased ( P &lt; 0.05) in A<jats:sub>1</jats:sub>AR<jats:sup>−/−</jats:sup>hearts compared with A<jats:sub>1</jats:sub>AR<jats:sup>+/+</jats:sup>hearts: 2.548 ± 0.1 vs. 2.059 ± 0.17 ml/min. In addition, selective activation of A<jats:sub>1</jats:sub>AR with 2-chloro- N<jats:sup>6</jats:sup>-cyclopentyladenosine (CCPA) at nanomolar concentrations (1–100 nM) did not significantly change coronary flow; at higher concentrations, CCPA increased coronary flow in A<jats:sub>1</jats:sub>AR<jats:sup>−/−</jats:sup>and A<jats:sub>1</jats:sub>AR<jats:sup>+/+</jats:sup>hearts. Because deletion of A<jats:sub>1</jats:sub>AR increased basal coronary flow, it is speculated that this effect is due to removal of an inhibitory influence associated with A<jats:sub>1</jats:sub>AR. Adenosine and NECA at approximately EC<jats:sub>50</jats:sub>(100 and 50 nM, respectively) increased coronary flow in A<jats:sub>1</jats:sub>AR<jats:sup>+/+</jats:sup>hearts to 177.86 ± 8.75 and 172.72 ± 17% of baseline, respectively. In the presence of the selective A<jats:sub>1</jats:sub>AR antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 50 nM), the adenosine- and NECA-induced increase in coronary flow in A<jats:sub>1</jats:sub>AR<jats:sup>+/+</jats:sup>hearts was significantly augmented to 216.106 ± 8.35 and 201.61 ± 21.89% of normalized baseline values, respectively. The adenosine- and NECA-induced increase in coronary flow in A<jats:sub>1</jats:sub>AR<jats:sup>−/−</jats:sup>hearts was not altered by DPCPX. These data indicate that A<jats:sub>1</jats:sub>AR may inhibit or negatively modulate coronary flow mediated by other AR subtypes (A<jats:sub>2A</jats:sub>and A<jats:sub>2B</jats:sub>).</jats:p>","journal":"American Journal of Physiology-Heart and Circulatory Physiology","year":2006,"id":671910,"datarank":0.5570358100056463,"base_score":3.713572066704308,"endowment":3.713572066704308,"self_citation_contribution":0.5570358100056463,"citation_network_contribution":0.0,"self_endowment_contribution":0.5570358100056463,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":546754,"name":"Bunyen Teng","orcid":"0000-0003-4121-987X","position":1,"is_corresponding":false},{"id":1116935,"name":"R. Ray Morrison","orcid":null,"position":2,"is_corresponding":false},{"id":1755426,"name":"J. Schnermann","orcid":null,"position":3,"is_corresponding":false},{"id":481161,"name":"S. Jamal Mustafa","orcid":"0000-0003-4677-6392","position":4,"is_corresponding":false},{"id":1755425,"name":"Huda E. Tawfik","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Role of A<sub>1</sub>adenosine receptor in the regulation of coronary flow","abstract":"<jats:p>To determine whether A<jats:sub>1</jats:sub>adenosine receptors (AR) participate in adenosine-induced changes of coronary flow, isolated hearts from A<jats:sub>1</jats:sub>AR<jats:sup>−/−</jats:sup>and A<jats:sub>1</jats:sub>AR<jats:sup>+/+</jats:sup>mice were perfused under constant pressure, and the effects of nonselective and selective agonists were examined. Adenosine, 5′- N-ethylcarboxamidoadenosine (NECA, nonselective), and the selective A<jats:sub>2A</jats:sub>AR agonist 2–2-carboxyethylphenethylamino-5′- N-ethylcarboxamidoadenosine (CGS-21680) augmented maximal coronary vasodilation in A<jats:sub>1</jats:sub>AR<jats:sup>−/−</jats:sup>hearts compared with A<jats:sub>1</jats:sub>AR<jats:sup>+/+</jats:sup>hearts. Basal coronary flow was increased ( P &lt; 0.05) in A<jats:sub>1</jats:sub>AR<jats:sup>−/−</jats:sup>hearts compared with A<jats:sub>1</jats:sub>AR<jats:sup>+/+</jats:sup>hearts: 2.548 ± 0.1 vs. 2.059 ± 0.17 ml/min. In addition, selective activation of A<jats:sub>1</jats:sub>AR with 2-chloro- N<jats:sup>6</jats:sup>-cyclopentyladenosine (CCPA) at nanomolar concentrations (1–100 nM) did not significantly change coronary flow; at higher concentrations, CCPA increased coronary flow in A<jats:sub>1</jats:sub>AR<jats:sup>−/−</jats:sup>and A<jats:sub>1</jats:sub>AR<jats:sup>+/+</jats:sup>hearts. Because deletion of A<jats:sub>1</jats:sub>AR increased basal coronary flow, it is speculated that this effect is due to removal of an inhibitory influence associated with A<jats:sub>1</jats:sub>AR. Adenosine and NECA at approximately EC<jats:sub>50</jats:sub>(100 and 50 nM, respectively) increased coronary flow in A<jats:sub>1</jats:sub>AR<jats:sup>+/+</jats:sup>hearts to 177.86 ± 8.75 and 172.72 ± 17% of baseline, respectively. In the presence of the selective A<jats:sub>1</jats:sub>AR antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 50 nM), the adenosine- and NECA-induced increase in coronary flow in A<jats:sub>1</jats:sub>AR<jats:sup>+/+</jats:sup>hearts was significantly augmented to 216.106 ± 8.35 and 201.61 ± 21.89% of normalized baseline values, respectively. The adenosine- and NECA-induced increase in coronary flow in A<jats:sub>1</jats:sub>AR<jats:sup>−/−</jats:sup>hearts was not altered by DPCPX. These data indicate that A<jats:sub>1</jats:sub>AR may inhibit or negatively modulate coronary flow mediated by other AR subtypes (A<jats:sub>2A</jats:sub>and A<jats:sub>2B</jats:sub>).</jats:p>","is_dataset_classified":null,"base_score":3.713572066704308,"endowment":3.713572066704308,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16517942","pmcid":null,"openalex_id":"https://openalex.org/W2171177648","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"HL-027339","title":null}],"total_grants":1,"fwci":2.5487,"citation_percentile":0.89038101,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":5},{"year":2014,"count":3},{"year":2015,"count":4},{"year":2016,"count":1},{"year":2021,"count":3},{"year":2025,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.physiology.org/doi/pdf/10.1152/ajpheart.01319.2005","host_type":"publisher"},{"url":"https://doi.org/10.1152/ajpheart.01319.2005","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16517942","host_type":"repository"}],"fields_of_study":["Adenosine and Purinergic Signaling","Cardiac electrophysiology and arrhythmias","Cardiac Arrhythmias and Treatments"],"mesh_terms":["Adaptation, Physiological","Animals","Coronary Circulation","Feedback","Heart Rate","Homeostasis","Mice, Inbred C57BL","Receptor, Adenosine A1","Mice","In Vitro Techniques"],"keywords":["Adenosine","CCPA","Adenosine receptor","Internal medicine","CGS-21680","Endocrinology","Agonist","Chemistry","Adenosine receptor antagonist","Coronary perfusion pressure","Vasodilation","Adenosine A1 receptor","Receptor","Cardiology","Medicine","Anesthesia"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T05:16:11.717555Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}