Abstract
OUR understanding of the regulation of vascular tone has been extended since the identification of vasoactive agents such as the atrial natriuretic peptides1, endothelial-derived relaxing factor2 and endothelin3. Unidentified vasopressive agents have been found in platelets4. Here we isolate these vasopressors and identify them as diadenosine pentaphosphate (AP5A) and diadenosine hex-aphosphate (AP6A) by chromatography, mass spectrometry, ultraviolet spectroscopy and enzymatic cleavage. In the vasculature of isolated perfused rat kidney, both diadenosine phosphates were active at a concentration of 10−9 M; in aortic rings, contractions were elicited at 10−8 M.Intra-aortic injection in the rat caused a prolonged increase in blood pressure. We conclude that AP5A and AP6A may play a part in local vasoregulation and possibly in the regulation of blood pressure.
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Flynn, T. G., De Bold, M. L. & De Bold, A. J. Biochem. biophys. Res. Commun. 117, 859–865 (1983).
Palmer, R. M. J., Ferrige, A. G. & Moncada, S. Nature 327, 524–526 (1987).
Yanagisawa, M. et al. Nature 332, 411–415 (1988).
Agha, A. et al. J. vasc. Res. 29, 281–289 (1992).
Ally, A. & Park, G. J. Chromatogr. 575, 19–27 (1992).
Pintor, J., Torres, M. & Miras-Portugal, M. T. Life Sci. 48, 2317–2324 (1991).
Rodriguez del Castillo, A., Torres, M., Delicado, E. G. & Miras-Portugal, M. T. J. Neurochem. 51, 1696–1703 (1988).
Pintor, J., Rotllan, P., Torres, M. & Miras-Portugal, M. T. Analyt. Biochem. 200, 296–300 (1992).
Harrison, M. J. & Brossmer, R. FEBS Lett. 54, 57–60 (1975).
Morii, H. & Makinose, M. Eur. J. Biochem. 205, 979–984 (1992).
Pohl, U., Ogilvie, A., Lamontagne, D. & Busse, R. Am. J. Physiol. 260, H1692–H1697 (1991).
Nees, S. Eur. Heart J. 10, suppl. F 28–35 (1989).
Busse, R., Ogilvie, A. & Pohl, U. Am. J. Physiol. 254, H828–H832 (1988).
Baril, E. F., Coughlin, S. A. & Zamecnik, P. C. Cancer Invest. 3, 465–471 (1985).
Yamaguchi, N., Kodama, M. & Ueda, K. Gastroenterology 89, 723–731 (1985).
Weinmann-Dorsch, C. et al. Eur. J. Biochem. 138, 179–185 (1984).
Zamecnik, P. C., Stephenson, M. L., Janeway, C. M. & Randerath, K. Biochem. biophys. Res. Commun. 24, 91–97 (1966).
Frenz, J., Van der Schrieck, P. & Horvath, C. J. Chromatogr. 330, 1–17 (1985).
Zidek, W. et al. Clin. Exp. Hypertens. A12, 365–381 (1990).
Grynkiewicz, G., Poenie, M. & Tsien, R. Y. J. biol. Chem. 260, 3440–3450 (1985).
Neusser, M., Golinski, P., Zhu, Z., Tepel, M. & Zidek, W. J. vasc. Res. 30, 116–120 (1993).
Nordhoff, E. et al. Rapid Comm. Mass Spectrom. 6, 771–776 (1992).
Sulkowski, E. & Laskowski, M. Biochim. biophys. Acta 240, 443–447 (1971).
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Schlüter, H., Offers, E., Brüggemann, G. et al. Diadenosine phosphates and the physiological control of blood pressure. Nature 367, 186–188 (1994). https://doi.org/10.1038/367186a0
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DOI: https://doi.org/10.1038/367186a0
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