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Adenosine-induced relaxation of cultured bovine retinal pericytes
T Matsugi1, Q Chen, D R Anderson
1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Florida, USA.
Purpose:
To investigate the effect of adenosine on the contractile tone of cultured bovine retinal pericytes.
Methods:
Changes in the contractile tone were quantified as the changes in the summed length of wrinkles induced by pericytes on the silicone surface on which the cells were grown.
Results:
Adenosine at 10(-9) M had no effect. In the range of 10(-8) to 10(-4) M, adenosine caused relaxation of pericytes in a concentration-dependent manner. Complete relaxation was induced by 10(-5) M to 10(-4) M adenosine. The concentration of adenosine that produced 50% relaxation was 3 x 10(-7) M. At all concentrations, relaxation began within 1 minute, reached the maximum within 5 to 10 minutes, and persisted for at least 30 minutes. After a washout of 3 x 10(-7) M adenosine, the reduced contractile tone recovered to the original level in 10 minutes. The adenosine-induced relaxation (3 x 10(-7) M) was completely abolished in the presence of 8-phenyl theophylline (10(-5) M), a nonselective adenosine receptor antagonist. The selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) at 10(-6) M did not reduce the effect of adenosine (3 x 10(-7) M). Conversely, the selective A2 receptor antagonist CP-66,713 at 10(-8) M partially inhibited (and at 10(-7) M, completely inhibited) the relaxation induced by adenosine (3 x 10(-7) M). The adenosine receptor antagonists-8-phenyl theophylline (10(-5) M), DPCPX (10(-6) M), and CP-66,713 (10(-7) M) by themselves had no effect on the contractile tone of pericytes.
Conclusions:
Adenosine causes relaxation of pericytes through the activation of the adenosine A2 receptor. Adenosine, which accumulates under ischemic conditions, may help to regulate local capillary blood flow.