Zh. Zhao et al., A role for the A3 adenosine receptor in determining tissue levels of cAMP and blood pressure: studies in knock-out mice, BBA-MOL BAS, 1500(3), 2000, pp. 280-290
Citations number
53
Categorie Soggetti
Medical Research General Topics
Journal title
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Adenosine administration has been reported to lower blood pressure by activ
ating specific membrane receptors. The rat and human heart and aorta have b
een previously found to express both A2-type adenosine receptors, which act
ivate adenylyl cyclase, and A3 adenosine receptors (A3AR), which inhibit ad
enylyl cyclase. In the current study, we used A3 adenosine receptor (A3AR)
knock-out mice to examine the hypothesis that the relative levels of the A2
-type adenosine receptors and A3AR determine the steady-state levels of cAM
P in the cells and may affect blood pressure. We found that the A3AR knocko
ut mice express normal levels of the A1- and A2-type adenosine receptors. I
n situ hybridization demonstrated that the level of A3AR is high in the vas
cular smooth muscle layer of aortas derived from wild-type mice, but is not
detectable in the knock-out mice. The steady-state level of cAMP is elevat
ed in the aorta and heart of knock-out mice, as compared to wildtype mice,
but is not altered in platelets, where A3AR is not expressed naturally. A3A
R knock-out mice possess a blood pressure comparable to this in wild-type m
ice. However, when challenged with adenosine, the knock-out mice display a
further increase in cAMP levels in the heart and vascular smooth muscle and
a significant decrease in blood pressure, as compared to wild-type mice. I
n contrast, the effect of adenosine on ADP-induced platelet aggregation is
similar in both types of mice. These studies indicate that the A3AR affects
the steady-state level of cAMP in the tissues where it is naturally expres
sed, and that it influences the blood pressure in response to adenosine. (C
) 2000 Elsevier Science B.V. All rights reserved.