HEMODYNAMIC-EFFECTS AND HISTAMINE-RELEASE ELICITED BY THE SELECTIVE ADENOSINE A(3) RECEPTOR AGONIST 2-CL-IB-MECA IN CONSCIOUS RATS

The hemodynamic effects of the novel, selective adenosine A(3) recepto r agonist -6-(3-iodobenzyl)adenosine-5'-N-methyl-carboxamide (2-Cl-IB- MECA) were investigated in conscious rats. Intravenous administration of 200 mu g/kg 2-Cl-IB-MECA resulted in a short-lasting hypotension, w hich was accompanied by a 50-100-fold increase in plasma histamine con centrations. Administration of a second dose of 2-Cl-IB-MECA did not e licit any hemodynamic effects. Also no histamine release was observed after the second dose. The observation of rapid tachyphylaxis in combi nation with histamine release suggests that mast cell mediator release plays a key role in the hemodynamic effects of adenosine A(3) recepto r agonists.