Abstract
Adrenal angiotensin II (AII) receptors have been pharmacologically and structurally divided into two main subtypes, AT1 and AT2. Radioligand receptor binding assays with125I-sarcosine1, isoleucine8 angiotensin II (125I-SI AII) in the presence of losartan, an AT1 selective ligand, and PD123177 an AT2 selective ligand, indicated that the AT1 subtype was predominant in membrane homogenates of the rat adrenal cortex (AT1 Bmax=649 ± 62 fmol/mg protein; AT2 Bmax=237 ± 29 fmol/mg protein). In membrane homogenates of the adrenal medulla, the AT2 subtype was predominant (AT1 Bmax=55 ± 5 fmol/mg protein; AT2 Bmax=109 ± 29 fmol/mg protein). Overall 58% of the125I-SI AII binding in the rat adrenal was to the AT1 subtypes, and 42% was to the AT2 subtypes. The outer cortex contained 59% of the AH receptor binding sites in the adrenal, while the medulla accounted for the remaining 41%. The affinity of the AT1 binding sites in membrane homogenates of the cortex and medulla (K D =672 ± 123 pM and 573 ± 85 pM, respectively) was not significantly different. The affinity for125I-SH AII of AT2 binding sites in membrane homogenates was higher than that of AT, binding sites. The affinity for125I-SI All of AT2 binding sites in membrane homogenates of the outer cortex (K D =265 ± 35 pM) was significantly less than that in the medulla (K D =133 ± 11 pM).In vitro receptor autoradiography also demonstrated that the AT2 subtype in frozen sections of the cortex had a lower affinity (K D =1512 ± 191 pM) than that in the medulla (K D =867 ± 72 pM). The heterogeneous affinity of adrenal AT2 binding sites may indicate existence of multiple AT2 receptor subtypes in the rat adrenal.
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References
Aguilera, G. (1992).Mol. Cell. Endocrinol.,90, 53–60.
Amara, S., Jonas, V., Rosenfeld, M.G., Ong, E.S. & Evans, R.M. (1982).Nature,298, 240–244.
Andersson, B. and Westbye, O. (1970).Life Sci.,9, Pt. 1, 601–608.
Balla, T., Baukal, A.J., Eng, S. and Catt, K.J. (1991).Mol. Pharmacol,40, 401–406.
Barker, S. (1993).Biochem. Biophys. Res. Comm.,192, 392–398.
Booth, D.A. (1968).J. Pharmacol. Exp. Ther.,160, 336–348.
Bottari, S., King, I.N., Reichlin, S., Dalhsoem, I., Lydon, N. & de Gasparo, M. (1992).Biochem. Biophys. Res. Comm.,183, 206–211.
Braun-Menendez, E., Fasciolo, J.C., Leloir, S.F and Munoz, J.M. (1940).J. Physiol.,98, 283–298.
Brechler, V., Jones, P.W., Levens, N., de Gasparo, M. & Bottari, S.P. (1993).Regul. Pept.,44, 207–213.
Canonico, P.L and MacLeod, R.M. (1986).Endocrinology,118, 233–238.
Catt, K.J., Mendelsohn, F.A., Millan, M.A. and Aguilera, G. (1984).J. Cardiovasc. Pharmacol.,6, S575-S586.
Chang, R.S.L. and Lotti, V.J. (1990).Mol. Pharmacol.,29, 347–351.
Chang, R.S.L., Lotti, V.J., Chen, T.B. and Faust, K.A. (1990).Biochem. Biophys. Res. Comm.,171, 813–817.
Chiu, A.T., Herblin, W.F., McCall, D.E. Ardecky, R.J., Carini, D.J., Duncia, J.V., Pease, L.J., Wong, P.C., Wexler, R.R., Johnson, A.L. & Timmermans, P.B.M.W.M. (1989a).Biochem. Biophys. Res. Comm.,165, 196–203.
Chiu, A.T., McCall, D.E., Nguyen, T.T., Carini, D.J., Duncia, J.V. Herblin, W.F., Uyeda, R.T., Wong, P.C., Wexler, R.R., Johnson, A.L. & Timmermans, P.B.M.W.M. (1989b).Eur. J. Pharmacol.,170, 117–118.
Chiu, A.T., Dunscomb, J., Kosierowski, J., Burton, C.R., Santomenna, L.D., Corjay, M.H. & Benfield, I. (1993).Biochem. Biophys. Res. Commun.,197, 440–449.
Cook, V.I., Grove, K.L., Speth, R.C., McMenamin, K.M. & Harding, J.W. (1991).Brain Res.,560, 334–336.
Devynck, M.A., Pernollet, M.G., Matthews, P.G., Khosla, M.C., Bumpus, F.M. & Meyer, P. (1977).Proc. Natl. Acad. Sci. USA,74, 4029–4032.
Dudley, D.T., Pancek, R.L., Major, T.C., Lu, G.H., Bruns, R.F., Klinkefus, B.A., Hodges, J.C. & Weishaar, R.E. (1990).Mol. Pharmacol.,38, 370–377.
Dudley, D.T., Hubbell, S.E and Summerfelt, R.M. (1991).Mol. Pharmacol.,40, 360–367.
Elton, T.S., Stephan, C.C., Taylor, G.R., Kimball, M.G., Martin, M.M., Durand, J.N. & Oparil, S.(1992).Biochem. Biophys. Res. Comm.,184, 1067–1073.
Epstein, A.N., Fitzsimons, J.T. and Rolls, B.J. (1970).J. Physiol.,210, 457–474.
Gehlert, D.R., Gackenheimer, S.L., Reel, J.K., Lin, H.-S. & Steinberg, M.I. (1990).Eur. J. Pharmacol.,187, 123–126.
Glossmann, H., Baukal, A.J. and Catt, K.J. (1974).J. Biol. Chem.,249, 825–834.
Grady, E.F., Sechi, L.A., Griffin, C.A., Schambelan, M. & Kalinyak, J.E. (1991).J. Clin. Invest.,88, 921–933.
Himeno, A., Nazarali, A.J and Saavedra, J.M. (1988).Regul. Pept.,23, 127–133.
Hughes, J. and Roth, R.H. (1971).Br. J. Pharmacol.,41, 239–255.
Iwai, N. and Inagami, T. (1992).FEBS Lett.,298, 257–260.
Kakar, S.S., Riel, K.K and Neill, J.D. (1992a).Biochem. Biophys. Res. Commun.,185, 688–692.
Kakar, S.S., Seller, J.C., Devor, D.C., Musgrove, L.C. & Neill, J.D. (1992b).Biochem. Biophys. Res. Commun.,183, 1090–1096.
Kambayashi, Y., Bardhan, S., Takahashi, K., Tsuzuki, S., Inui, H., Hamakubo, T. & Inagami, T. (1993).J. Biol. Chem.,268, 24543–24546.
Keil, L.C., Summy-Long, J. and Severs, W.B. (1975).Endocrinology,96, 1063–1065.
Laragh, J.H., Angers, M., Kelly, W.G. and Lieberman, S. (1960).JAMA,174, 234–240.
Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951).J. Biol. Chem.,193, 265–275.
Lu, X.-Y., Zhang, W., Grove, K.L. and Speth, R.C. (1994).J. Pharmacol. Meth. In press.
Mains, R.E., Eipper, B.A. and Ling, N. (1977).Proc. Natl. Acad. Sci. USA,74, 3014–3018.
Millan, M.A., Jacobowitz, D.M., Aguilera, G. and Catt, K.J. (1991).Proc. Natl. Acad. Sci. USA,88, 11440–11444.
Mukoyama, M., Nakajima, M., Horiuchi, M., Sasamura, H., Pratt, R.E. & Dzau, V.J. (1993).J. Biol. Chem.,268, 24539–24542.
Murphy, T.J., Alexander, R.W., Griendling, K.K., Runge, M.S. & Bernstein, K.E. (1991).Nature,351, 233–236.
Nakajima, M., Mukoyama, M., Pratt, R.E., Horiuchi, M. & Dzau, V.J. (1993).Biochem. Biophys. Res. Commun.,197, 393–399.
Page, I.H. and Helmer, O.M. (1940).J. Exp. Med.,71, 29.
Pucell, A.G., Hodges, J.C., Sen, I., Bumpus, F.M. & Husain, A. (1991).Endocrinology,128, 1947–1959.
Rosenthal, H.E. (1967).Anal. Biochem.,20, 525–532.
Rowe, B.P., Grove, K.L., Saylor, D.L. and Speth, R.C. (1990).Eur. J. Pharmacol.,186, 339–342.
Rowe, B.P., Saylor, D.L. and Speth, R.C. (1992).Neuroendocrinology,55, 563–573.
Sasaki, K., Yamano, Y., Bardhan, S., Iwai, N., Murray, J.J., Hasegawa, M., Matsuda, Y. & Inagami, T. (1991).Nature,351, 230–233.
Sasamura, H., Hein, L., Krieger, J.E., Pratt, R.E., Kobilka, B.K. & Dzau, V.J. (1992).Biochem. Biophys. Res. Commun.,185, 253–259.
Servant, G., Dudley, D.T., Escher, E. and Guillemette, G. (1994).Mol. Pharmacol.,45, 1112–1118.
Singh, R., Harding, J.W. and Speth, R.C. (1986).Eur. J. Pharmacol.,120, 319–327.
Speth, R.C., Rowe, B.P., Grove, K.L., Carter, M.R. & Saylor, D.L. (1991).Brain Res.,548, 1–8.
Speth, R.C. (1993).Regul. Pept.,44, 189–197.
Speth, R.C. and Kim, K.H. (1990).Biochem. Biophys. Res. Comm.,169, 997–1006.
Sumners, C., Tang, W., Zelezna, B. and Raizada, M.K. (1991).Proc. Natl. Acad. Sci. USA,88, 7567–7571.
Timmermans, P.B.M.W.M., Wong, P.C., Chiu, A.T. and Herblin, W.F. (1991).TIPS,12, 55–62.
Timmermans P.B., Wong, P.C., Chiu, A.T., Herblin, W.F., Benfield, P., Carini, D.J., Lee, R.J., Wexler, R.R., Saye, J.A. & Smith, R.D. (1993).Pharmacol. Rev.,45, 205–251.
Tsutsumi, K. and Saavedra, J.M. (1991).Endocrinology,129, 3001–3008.
Tsutsumi, K. and Saavedra, J.M. (1992).Mol. Pharmacol.,41, 290–297.
Tsuzuki, S., Ichiki, T., Nakakubo, H., Kitami, Y., Guo, D.F., Shirai, H. & Inagami, T. (1994).Biochem. Biophys. Res. Commun.,200, 1449–1454.
Webb, M.L., Liu, E.C-K., Cohen, R.B., Hedberg, A., Bogosian, E.A., Monshizadegan, H., Molloy, C., Serafino, R., Moreland, S., Murphy, T.J. & Dickinson, K.E.J. (1992).Peptides,13, 499–508.
Whitebread, S., Mele, M., Kamber, B. and de Gasparo, M. (1989).Biochem. Biophys. Res. Comm.,163, 284–291.
Wiest, S.A., Rampersaud, A., Zimmerman, K. and Steinberg, M.I. (1991).J. Cardiovasc. Pharmacol.,17, 177–184.
Zimmerman, B.G. and Whitmore, L. (1967).Int. J. Neuropharmacoi,6, 27–38.
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Lu, X.Y., Grove, K.L., Zhang, W. et al. Pharmacological characterization of angiotensin II AT2 receptor subtype heterogeneity in the rat adrenal cortex and medulla. Endocr 3, 255–261 (1995). https://doi.org/10.1007/BF03021402
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DOI: https://doi.org/10.1007/BF03021402