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Intracellular signalling pathways in the vasoconstrictor response of mouse afferent arterioles to adenosine
Author(s) -
Hansen P. B.,
Friis U. G.,
Uhrenholt T. R.,
Briggs J.,
Schnermann J.
Publication year - 2007
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2007.01724.x
Subject(s) - adenosine , afferent arterioles , vasoconstriction , chemistry , medicine , thapsigargin , endocrinology , calcium , biology , angiotensin ii , biochemistry , receptor
Aims: Adenosine causes vasoconstriction of afferent arterioles of the mouse kidney through activation of adenosine A 1 receptors and Gi‐mediated stimulation of phospholipase C. In the present study, we further explored the signalling pathways by which adenosine causes arteriolar vasoconstriction. Methods and results: Adenosine (10 −7 m ) significantly increased the intracellular calcium concentration in mouse isolated afferent arterioles measured by fura‐2 fluorescence. Pre‐treatment with thapsigargin (2 μ m ) blocked the vasoconstrictor action of adenosine (10 −7 m ) indicating that release of calcium from the sarcoplasmic reticulum (SR), stimulated presumably by IP 3 , is involved in the adenosine contraction mechanism of the afferent arteriole. In agreement with this notion is the observation that 2 aminoethoxydiphenyl borate (100 μ m ) blocked the adenosine‐induced constriction whereas the protein kinase C inhibitor calphostin C had no effect. The calcium‐activated chloride channel inhibitor IAA‐94 (30 μ m ) inhibited the adenosine‐mediated constriction. Patch clamp experiments showed that adenosine treatment induced a depolarizing current in preglomerular smooth muscle cells which was abolished by IAA‐94. Furthermore, the vasoconstriction caused by adenosine was significantly inhibited by 5 μ m nifedipine (control 8.3 ± 0.2 μ m, ado 3.6 ± 0.6 μ m, ado + nifedipine 6.8 ± 0.2 μ m) suggesting involvement of voltage‐dependent calcium channels. Conclusion: We conclude that adenosine mediates vasoconstriction of afferent arterioles through an increase in intracellular calcium concentration resulting from release of calcium from the SR followed by activation of Ca 2+ ‐activated chloride channels leading to depolarization and influx of calcium through voltage‐dependent calcium channels.