Hemodynamic effects and histamine release elicited by the selective adenosine A3 receptor agonist 2-Cl-IB-MECA in conscious rats.
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.
Van Schaick
E A
EA
Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University, Netherlands.
Jacobson
K A
KA
Kim
H O
HO
IJzerman
A P
AP
Danhof
M
M
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000097:blood; D006636:Histamine Release / Q000187:drug effects*; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar
D058906:Purinergic P1 Receptor Agonists; D006632:Histamine; D000241:Adenosine; C090034:2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide