Intracellular signalling pathways in the vasoconstrictor response of mouse afferent arterioles to adenosine
Source: Acta Physiologica, Volume 191, Number 2, October 2007 , pp. 89-97(9)
Abstract:Aims: Adenosine causes vasoconstriction of afferent arterioles of the mouse kidney through activation of adenosine A1 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 μm) blocked the vasoconstrictor action of adenosine (10−7 m) indicating that release of calcium from the sarcoplasmic reticulum (SR), stimulated presumably by IP3, is involved in the adenosine contraction mechanism of the afferent arteriole. In agreement with this notion is the observation that 2 aminoethoxydiphenyl borate (100 μm) 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 μm) 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 μmnifedipine (control 8.3 ± 0.2 μm, ado 3.6 ± 0.6 μm, ado + nifedipine 6.8 ± 0.2 μm) 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 Ca2+-activated chloride channels leading to depolarization and influx of calcium through voltage-dependent calcium channels.
Document Type: Research article
Affiliations: 1: Department of Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark 2: National Institute of Diabetes, and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA
Publication date: 2007-10-01