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. 1984 Mar;81(5):1575–1579. doi: 10.1073/pnas.81.5.1575

Autoradiographic localization of angiotensin II receptors in rat brain.

F A Mendelsohn, R Quirion, J M Saavedra, G Aguilera, K J Catt
PMCID: PMC344880  PMID: 6324205

Abstract

The 125I-labeled agonist analog [1-sarcosine]-angiotensin II ( [Sar1]AII) bound with high specificity and affinity (Ka = 2 X 10(9) M-1) to a single class of receptor sites in rat brain. This ligand was used to analyze the distribution of AII receptors in rat brain by in vitro autoradiography followed by computerized densitometry and color coding. A very high density of AII receptors was found in the subfornical organ, paraventricular and periventricular nuclei of the hypothalamus, nucleus of the tractus solitarius, and area postrema. A high concentration of receptors was found in the suprachiasmatic nucleus of the hypothalamus, lateral olfactory tracts, nuclei of the accessory and lateral olfactory tracts, triangular septal nucleus, subthalamic nucleus, locus coeruleus, and inferior olivary nuclei. Moderate receptor concentrations were found in the organum vasculosum of the lamina terminalis, median preoptic nucleus, medial habenular nucleus, lateral septum, ventroposterior thalamic nucleus, median eminence, medial geniculate nucleus, superior colliculus, subiculum, pre- and parasubiculum, and spinal trigeminal tract. Low concentrations of sites were seen in caudate-putamen, nucleus accumbens, amygdala, and gray matter of the spinal cord. These studies have demonstrated that AII receptors are distributed in a highly characteristic anatomical pattern in the brain. The high concentrations of AII receptors at numerous physiologically relevant sites are consistent with the emerging evidence for multiple roles of AII as a neuropeptide in the central nervous system.

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Selected References

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  1. Aguilera G., Hyde C. L., Catt K. J. Angiotensin II receptors and prolactin release in pituitary lactotrophs. Endocrinology. 1982 Oct;111(4):1045–1050. doi: 10.1210/endo-111-4-1045. [DOI] [PubMed] [Google Scholar]
  2. Akaishi T., Negoro H., Kobayasi S. Responses of paraventricular and supraoptic units to angiotensin II, sar1-ile8-angiotensin II and hypertonic NaCl administered into the cerebral ventricle. Brain Res. 1980 Apr 28;188(2):499–511. doi: 10.1016/0006-8993(80)90048-7. [DOI] [PubMed] [Google Scholar]
  3. Barden N., Chevillard C., Saavedra J. M. Effects of acute and chronic 17-beta-estradiol administration on rhombencephalic, pineal and pituitary catecholamine levels in ovariectomized rats. Neuroendocrinology. 1982;35(2):123–127. doi: 10.1159/000123366. [DOI] [PubMed] [Google Scholar]
  4. Baxter C. R., Horvath J. S., Duggin G. G., Tiller D. J. Effect of age on specific angiotensin II-binding sites in rat brain. Endocrinology. 1980 Mar;106(3):995–999. doi: 10.1210/endo-106-3-995. [DOI] [PubMed] [Google Scholar]
  5. Bennett J. P., Jr, Snyder S. H. Angiotensin II binding to mammalian brain membranes. J Biol Chem. 1976 Dec 10;251(23):7423–7430. [PubMed] [Google Scholar]
  6. Bennett J. P., Jr, Snyder S. H. Receptor binding interactions of the angiotensin II antagonist, 125I-[sarcosine1,leucine8]angiotensin II, with mammalian brain and peripheral tissues. Eur J Pharmacol. 1980 Oct 3;67(1):11–25. doi: 10.1016/0014-2999(80)90003-5. [DOI] [PubMed] [Google Scholar]
  7. Biegon A., Rainbow T. C. Localization and characterization of [3H]desmethylimipramine binding sites in rat brain by quantitative autoradiography. J Neurosci. 1983 May;3(5):1069–1076. doi: 10.1523/JNEUROSCI.03-05-01069.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brownfield M. S., Reid I. A., Ganten D., Ganong W. F. Differential distribution of immunoreactive angiotensin and angiotensin-converting enzyme in rat brain. Neuroscience. 1982 Jul;7(7):1759–1769. doi: 10.1016/0306-4522(82)90033-1. [DOI] [PubMed] [Google Scholar]
  9. Capponi A. M., Catt K. J. Angiotensin II receptors in adrenal cortex and uterus. Binding and activation properties of angiotensin analogues. J Biol Chem. 1979 Jun 25;254(12):5120–5127. [PubMed] [Google Scholar]
  10. Changaris D. G., Severs W. B., Keil L. C. Localization of angiotensin in rat brain. J Histochem Cytochem. 1978 Jul;26(7):593–607. doi: 10.1177/26.7.357644. [DOI] [PubMed] [Google Scholar]
  11. Chen F. M., Healy D. P., Hawkins R., Printz M. P. Chronic infusion of angiotensin II into the olfactory bulb elicits an increase in water intake. Brain Res. 1983 Jan 24;259(2):335–339. doi: 10.1016/0006-8993(83)91270-2. [DOI] [PubMed] [Google Scholar]
  12. Chevillard C., Saavedra J. M. Distribution of angiotensin-converting enzyme activity in specific areas of the rat brain stem. J Neurochem. 1982 Jan;38(1):281–284. doi: 10.1111/j.1471-4159.1982.tb10883.x. [DOI] [PubMed] [Google Scholar]
  13. Felix D., Akert K. The effect of angiotensin II on neurones of the cat subfornical organ. Brain Res. 1974 Aug 16;76(2):350–353. doi: 10.1016/0006-8993(74)90468-5. [DOI] [PubMed] [Google Scholar]
  14. Ganten D., Speck G. The brain renin-angiotensin system: a model for the synthesis of peptides in the brain. Biochem Pharmacol. 1978;27(20):2379–2389. doi: 10.1016/0006-2952(78)90348-9. [DOI] [PubMed] [Google Scholar]
  15. Gaudreau P., Quirion R., St-Pierre S., Pert C. B. Tritium-sensitive film autoradiography of [3H]cholecystokinin-5/pentagastrin receptors in rat brain. Eur J Pharmacol. 1983 Jan 28;87(1):173–174. doi: 10.1016/0014-2999(83)90071-7. [DOI] [PubMed] [Google Scholar]
  16. Goochee C., Rasband W., Sokoloff L. Computerized densitometry and color coding of [14C] deoxyglucose autoradiographs. Ann Neurol. 1980 Apr;7(4):359–370. doi: 10.1002/ana.410070414. [DOI] [PubMed] [Google Scholar]
  17. Goodman R. R., Snyder S. H., Kuhar M. J., Young W. S., 3rd Differentiation of delta and mu opiate receptor localizations by light microscopic autoradiography. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6239–6243. doi: 10.1073/pnas.77.10.6239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gregg C. M., Malvin R. L. Localization of central sites of action of angiotensin II on ADH release in vitro. Am J Physiol. 1978 Feb;234(2):F135–F140. doi: 10.1152/ajprenal.1978.234.2.F135. [DOI] [PubMed] [Google Scholar]
  19. Hall M. M., Khosla M. C., Khairallah P. A., Bumpus F. M. Angiotensin analogs: the influence of sarcosine substituted in position 1. J Pharmacol Exp Ther. 1974 Jan;188(1):222–228. [PubMed] [Google Scholar]
  20. Harding J. W., Stone L. P., Wright J. W. The distribution of angiotensin II binding sites in rodent brain. Brain Res. 1981 Feb 2;205(2):265–274. doi: 10.1016/0006-8993(81)90338-3. [DOI] [PubMed] [Google Scholar]
  21. Herkenham M., Pert C. B. Light microscopic localization of brain opiate receptors: a general autoradiographic method which preserves tissue quality. J Neurosci. 1982 Aug;2(8):1129–1149. doi: 10.1523/JNEUROSCI.02-08-01129.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hirose S., Yokosawa H., Inagami T. Immunochemical identification of renin in rat brain and distinction from acid proteases. Nature. 1978 Jul 27;274(5669):392–393. doi: 10.1038/274392a0. [DOI] [PubMed] [Google Scholar]
  23. Huwyler T., Felix D. Angiotensin II-sensitive neurons in septal areas of the rat. Brain Res. 1980 Aug 11;195(1):187–195. doi: 10.1016/0006-8993(80)90876-8. [DOI] [PubMed] [Google Scholar]
  24. Inagami T., Celio M. R., Clemens D. L., Lau D., Takii Y., Kasselberg A. G., Hirose S. Renin in rat and mouse brain: immunohistochemical identification and localization. Clin Sci (Lond) 1980 Dec;59 (Suppl 6):49s–51s. doi: 10.1042/cs059049s. [DOI] [PubMed] [Google Scholar]
  25. Keil L. C., Summy-Long J., Severs W. B. Release of vasopressin by angiotensin II. Endocrinology. 1975 Apr;96(4):1063–1065. doi: 10.1210/endo-96-4-1063. [DOI] [PubMed] [Google Scholar]
  26. Kilcoyne M. M., Hoffman D. L., Zimmerman E. A. Immunocytochemical localization of angiotensin II and vasopressin in rat hypothalamus: evidence for production in the same neuron. Clin Sci (Lond) 1980 Dec;59 (Suppl 6):57s–60s. doi: 10.1042/cs059057s. [DOI] [PubMed] [Google Scholar]
  27. Landas S., Phillips M. I., Stamler J. F., Raizada M. K. Visualization of specific angiotensin II binding sites in the brain by fluorescent microscopy. Science. 1980 Nov 14;210(4471):791–793. doi: 10.1126/science.6254147. [DOI] [PubMed] [Google Scholar]
  28. Mangiapane M. L., Thrasher T. N., Keil L. C., Simpson J. B., Ganong W. F. Deficits in drinking and vasopressin secretion after lesions of the nucleus medianus. Neuroendocrinology. 1983 Jul;37(1):73–77. doi: 10.1159/000123518. [DOI] [PubMed] [Google Scholar]
  29. Mendelsohn F. A., Aguilera G., Saavedra J. M., Quirion R., Catt K. J. Characteristics and regulation of angiotensin II receptors in pituitary, circumventricular organs and kidney. Clin Exp Hypertens A. 1983;5(7-8):1081–1097. doi: 10.3109/10641968309048843. [DOI] [PubMed] [Google Scholar]
  30. Mendelsohn F. A., Csicsmann J., Hutchinson J. S., DiNicolantonio R., Takata Y. Modulation of brain angiotensin-converting enzyme by dietary sodium and chronic intravenous and intracerebroventricular fusion of angiotensin II. Hypertension. 1982 Sep-Oct;4(5):590–596. doi: 10.1161/01.hyp.4.5.590. [DOI] [PubMed] [Google Scholar]
  31. Miselis R. R., Shapiro R. E., Hand P. J. Subfornical organ efferents to neural systems for control of body water. Science. 1979 Sep 7;205(4410):1022–1025. doi: 10.1126/science.472723. [DOI] [PubMed] [Google Scholar]
  32. Munson P. J., Rodbard D. Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem. 1980 Sep 1;107(1):220–239. doi: 10.1016/0003-2697(80)90515-1. [DOI] [PubMed] [Google Scholar]
  33. Naruse K., Takii Y., Inagami T. Immunohistochemical localization of renin in luteinizing hormone-producing cells of rat pituitary. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7579–7583. doi: 10.1073/pnas.78.12.7579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nicoll R. A., Barker J. L. Excitation of supraoptic neurosecretory cells by angiotensin II. Nat New Biol. 1971 Oct 6;233(40):172–174. doi: 10.1038/newbio233172a0. [DOI] [PubMed] [Google Scholar]
  35. Quinlan J. T., Phillips M. I. Immunoreactivity for an angiotensin II-like peptide in the human brain. Brain Res. 1981 Jan 26;205(1):212–218. doi: 10.1016/0006-8993(81)90735-6. [DOI] [PubMed] [Google Scholar]
  36. Quirion R. Autoradiographic localization of a calcium channel antagonist, [3H]nitrendipine, binding site in rat brain. Neurosci Lett. 1983 Apr 29;36(3):267–271. doi: 10.1016/0304-3940(83)90011-3. [DOI] [PubMed] [Google Scholar]
  37. Quirion R., Bowen W. D., Herkenham M., Pert C. B. Visualization and solubilization of rat brain opiate receptors with a "kappa" ligand selectivity pattern. Cell Mol Neurobiol. 1982 Dec;2(4):333–346. doi: 10.1007/BF00710853. [DOI] [PubMed] [Google Scholar]
  38. Quirion R., Gaudreau P., St-Pierre S., Rioux F., Pert C. B. Autoradiographic distribution of [3H]neurotensin receptors in rat brain: visualization by tritium-sensitive film. Peptides. 1982 Sep-Oct;3(5):757–763. doi: 10.1016/0196-9781(82)90011-0. [DOI] [PubMed] [Google Scholar]
  39. Quirion R., Hammer R. P., Jr, Herkenham M., Pert C. B. Phencyclidine (angel dust)/sigma "opiate" receptor: visualization by tritium-sensitive film. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5881–5885. doi: 10.1073/pnas.78.9.5881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Quirion R., Shults C. W., Moody T. W., Pert C. B., Chase T. N., O'Donohue T. L. Autoradiographic distribution of substance P receptors in rat central nervous system. Nature. 1983 Jun 23;303(5919):714–716. doi: 10.1038/303714a0. [DOI] [PubMed] [Google Scholar]
  41. Rainbow T. C., Bleisch W. V., Biegon A., McEwen B. S. Quantitative densitometry of neurotransmitter receptors. J Neurosci Methods. 1982 Jan;5(1-2):127–138. doi: 10.1016/0165-0270(82)90059-0. [DOI] [PubMed] [Google Scholar]
  42. Ramsay D. J., Keil L. C., Sharpe M. C., Shinsako J. Angiotensin II infusion increases vasopressin, ACTH, and 11-hydroxycorticosteroid secretion. Am J Physiol. 1978 Jan;234(1):R66–R71. doi: 10.1152/ajpregu.1978.234.1.R66. [DOI] [PubMed] [Google Scholar]
  43. Roth K. A., Weber E., Barchas J. D., Chang D., Chang J. K. Immunoreactive dynorphin-(1-8) and corticotropin- releasing factor in subpopulation of hypothalamic neurons. Science. 1983 Jan 14;219(4581):189–191. doi: 10.1126/science.6129700. [DOI] [PubMed] [Google Scholar]
  44. Roth R. H. Action of angiotensin on adrenergic nerve endings: enhancement of norepinephrine biosynthesis. Fed Proc. 1972 Jul-Aug;31(4):1358–1364. [PubMed] [Google Scholar]
  45. Saavedra J. M., Fernandez-Pardal J., Chevillard C. Angiotensin-converting enzyme in discrete areas of the rat forebrain and pituitary gland. Brain Res. 1982 Aug 12;245(2):317–325. doi: 10.1016/0006-8993(82)90814-9. [DOI] [PubMed] [Google Scholar]
  46. Sakai K. K., Marks B. H., George J., Koestner A. Specific angiotensin II receptors in organ-cultured canine supra-optic nucleus cells. Life Sci. 1974 Apr 1;14(7):1337–1344. doi: 10.1016/0024-3205(74)90442-1. [DOI] [PubMed] [Google Scholar]
  47. Saltman S., Baukal A., Waters S., Bumpus F. M., Catt K. J. Competitive binding activity of angiotensin II analogues in an adrenal cortex radioligand-receptor assay;. Endocrinology. 1975 Aug;97(2):275–282. doi: 10.1210/endo-97-2-275. [DOI] [PubMed] [Google Scholar]
  48. Severs W. B., Daniels-Severs A. E. Effects of angiotensin on the central nervous system. Pharmacol Rev. 1973 Sep;25(3):415–449. [PubMed] [Google Scholar]
  49. Share L. Interrelations between vasopressin and the renin-angiotensin system. Fed Proc. 1979 Aug;38(9):2267–2271. [PubMed] [Google Scholar]
  50. Simpson J. B. The circumventricular organs and the central actions of angiotensin. Neuroendocrinology. 1981 Apr;32(4):248–256. doi: 10.1159/000123167. [DOI] [PubMed] [Google Scholar]
  51. Sirett N. E., McLean A. S., Bray J. J., Hubbard J. I. Distribution of angiotensin II receptors in rat brain. Brain Res. 1977 Feb 18;122(2):299–312. doi: 10.1016/0006-8993(77)90296-7. [DOI] [PubMed] [Google Scholar]
  52. Sirett N. E., Thornton S. N., Hubbard J. I. Angiotensin binding and pressor activity in the rat ventricular system and midbrain. Brain Res. 1979 Apr 20;166(1):139–148. doi: 10.1016/0006-8993(79)90655-3. [DOI] [PubMed] [Google Scholar]
  53. Strittmatter S. M., Kapiloff M. S., Snyder S. H. [3H]Captopril binding to membrane associated angiotensin converting enzyme. Biochem Biophys Res Commun. 1983 May 16;112(3):1027–1033. doi: 10.1016/0006-291x(83)91721-7. [DOI] [PubMed] [Google Scholar]
  54. Swanson L. W., Kucharczyk J., Mogenson G. J. Autoradiographic evidence for pathways from the medial preoptic area to the midbrain involved in the drinking response to angiotensin II. J Comp Neurol. 1978 Apr 15;178(4):645–659. doi: 10.1002/cne.901780404. [DOI] [PubMed] [Google Scholar]
  55. Tonnaer J. A., Engels G. M., Voshart K., Wiegant V. M., de Jong W. Binding of angiotensins to rat brain tissue: structure activity relationship. Brain Res Bull. 1983 Mar;10(3):295–300. doi: 10.1016/0361-9230(83)90093-x. [DOI] [PubMed] [Google Scholar]
  56. Weyhenmeyer J. A., Phillips M. I. Angiotensin-like immunoreactivity in the brain of the spontaneously hypertensive rat. Hypertension. 1982 Jul-Aug;4(4):514–523. doi: 10.1161/01.hyp.4.4.514. [DOI] [PubMed] [Google Scholar]
  57. Yang H. Y., Neff N. H. Distribution and properties of angiotensin converting enzyme of rat brain. J Neurochem. 1972 Oct;19(10):2443–2450. doi: 10.1111/j.1471-4159.1972.tb01298.x. [DOI] [PubMed] [Google Scholar]
  58. Young W. S., 3rd, Kuhar M. J. Neurotensin receptor localization by light microscopic autoradiography in rat brain. Brain Res. 1981 Feb 16;206(2):273–285. doi: 10.1016/0006-8993(81)90532-1. [DOI] [PubMed] [Google Scholar]
  59. Young W. S., 3rd, Kuhar M. J. Noradrenergic alpha 1 and alpha 2 receptors: light microscopic autoradiographic localization. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1696–1700. doi: 10.1073/pnas.77.3.1696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. van Houten M., Schiffrin E. L., Mann J. F., Posner B. I., Boucher R. Radioautographic localization of specific binding sites for blood-borne angiotensin II in the rat brain. Brain Res. 1980 Mar 31;186(2):480–485. doi: 10.1016/0006-8993(80)90995-6. [DOI] [PubMed] [Google Scholar]

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