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Hemodynamic effects and histamine release elicited by the selective adenosine A3 receptor agonist 2-Cl-IB-MECA in
E A Van Schaick1, K A Jacobson, H O Kim
1Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University, Netherlands.
Abstract:
The hemodynamic effects of the novel, selective adenosine A3 receptor agonist 2-chloro-N6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (2-Cl-IB-MECA) were investigated in conscious rats. Intravenous administration of 200 micrograms/kg 2-Cl-IB-MECA resulted in a short-lasting hypotension, which was accompanied by a 50-100-fold increase in plasma histamine concentrations. Administration of a second dose of 2-Cl-IB-MECA did not elicit any hemodynamic effects. Also no histamine release was observed after the second dose. The observation of rapid tachyphylaxis in combination with histamine release suggests that mast cell mediator release plays a key role in the hemodynamic effects of adenosine A3 receptor agonists.