Elsevier

Neuroscience

Volume 7, Issue 7, July 1982, Pages 1759-1769
Neuroscience

Differential distribution of immunoreactive angiotensin and angiotensin-converting enzyme in rat brain

https://doi.org/10.1016/0306-4522(82)90033-1Get rights and content

Abstract

To help resolve the controversy about the brain renin-angiotensin system, the distribution of immunoreactive angiotensin in the brains of male rats was analyzed using twelve different antibodies to angiotensin II, two of which had previously been reported to stain nerve fibers in the central nervous system. The distribution of angiotensin-converting enzyme immunoreactivity was also examined using an antibody to rabbit lung converting enzyme, and the distribution of this immunoreactivity was compared to that of immunoreactive angiotensin.

Weak angiotensin-like immunoreactivity was found in cell bodies of the hypothalamic magnocellular nuclei of colchicine-treated rats and in nerve terminals of the median eminence, neurohypophysis. central nucleus of the amygdala, bed nucleus of the stria terminalis and various other sites in the brain and spinal cord of untreated rats. Staining could be demonstrated with only three antisera. Antigenic specificity was carefully studied in these antisera. Each was similar in that staining could be blocked with angiotensins I, II or III and tetradecapeptide renin substrate, although angiotensins II and III were most potent. Because of the relatively few angiotensin II antisera which could stain brain and because they are blockable with angiotensin I and tetradecapeptide renin substrate, the precise nature of immunoreactive angiotensin remains an open question.

Intense converting enzyme-like activity was localized in endothelial cells of capillaries throughout the brain, in the subfornical organ and in the ‘brush border’ of choroidal epithelial cells in contact with cerebrospinal fluid. No activity was detected in neural tissue other than the subfornical organ and occasional weak activity in some ependymal elements elsewhere.

These findings indicate that angiotensin and converting enzyme immunoreactivities are not co-distributed and raises several questions regarding the nature of, and pathway for, formation of immunoreactive angiotensin in the brain.

References (39)

  • RamsayD.S.

    The brain renin-angiotensions system: a re-evaluation

    Neuroscience

    (1979)
  • RixE. et al.

    Converting enzyme in the choroid plexus, brain, and kidney: immunocytochemical studies in rats

    Neuroscience Letters

    (1981)
  • VandesandeF.

    A critical review of immunocytochemical methods for light microscopy

    J. Neurosci. Meth.

    (1979)
  • Van HoutenM. et al.

    Radioantographic localization of specific sites for blood-borne angiotensin II in the rat brain

    Brain Res.

    (1980)
  • ZimmermanE.A. et al.

    Exploration peptidexic pathways in brain by immunocytochemistry: a ten year perspective

    Peptides

    (1980)
  • BrownfieldM.S.

    Distribution of neurophysin, oxytoin and vasopressin in the rat

    Ph.D. Thesis Dissertation Abstracts

    (1979)
  • CaldwellP.B. et al.

    Angiotensin-converting enzyme: vascular endothelial localization

    Science, N.Y.

    (1976)
  • ChangarisD.C. et al.

    Angiotensin II immunohistochemistry of the rat brain

    Neuroendocrinology

    (1978)
  • DasM. et al.

    Pulmonary angiotensin-converting enzyme antienzyme antibody

    Biochemistry

    (1976)
  • Cited by (159)

    • Anxiogenic-like effects induced by hemopressin in rats

      2015, Pharmacology Biochemistry and Behavior
      Citation Excerpt :

      In comparative analyses, using bradykinin as a standard substrate for these three enzymes, which was then considered 100% of relative ratio of hydrolysis in a given period of time at maximal enzymatic velocity, it was shown that HP is hydrolyzed 152.24% by EP24.16, 140% by EP24.15 and 1146.19% by ACE (Rioli et al., 2003). The presence of these peptidases in peripheral and brain tissue is well documented (Cicilini et al., 1977; Chevillard and Saavedra, 1982; Brownfield et al., 1982; Massarelli et al., 1999; Fontenele-Neto et al., 2001), suggesting that HP could be efficiently degraded following i.p. or I.C.V. administration. HP can be hydrolyzed by EP24.15 and/or EP24.16 in different peptide bonds to generate the N-terminal fragments PVNF, PVNFK and/or PVNFKF (Rioli et al., 2003).

    • Angiotensin II and CRF receptors in the central nucleus of the amygdala mediate hemodynamic response variability to cocaine in conscious rats

      2010, Brain Research
      Citation Excerpt :

      Ang receptors in the CNS play an important role in autonomic and neurohumoral responses to behavioral and pharmacological stress (Jezova et al., 1998; Knuepfer et al., 2005; Rowe et al., 2006; Saiki et al., 1997). Ang and AT1 receptors exist in the amygdala and, in particular, in the CeA (Brownfield et al., 1982; von Bohlen und Halbach and Albrecht, 1998). Microinjection of Ang in the amygdala of the rat increases the discharge rate of amygdalar neurons and the increase can be blocked by either AT1 or AT2 receptor antagonists (Albrecht et al., 2000).

    • Angiotensin type-1-receptor antagonists reduce 6-hydroxydopamine toxicity for dopaminergic neurons

      2007, Neurobiology of Aging
      Citation Excerpt :

      Furthermore, ACE occurs in neurons, and high concentrations of ACE have been observed in the striatum and substantia nigra of mammals including rats [14] and humans [13]. Immunohistochemical location of AII, as well as of AII-ir terminals, has been reported in the human and rat striatum [8,52]. AT1 receptors occur in DA neurons, both in cell bodies in the substantia nigra and their terminal fields in the striatum of different mammals, including rats and humans, as revealed by autoradiography [1,2,15,58] and subsequently confirmed by immunohistochemistry [4,54] and in situ hybridization histochemistry [38].

    View all citing articles on Scopus
    *

    Current address: Dr. M.S. Brownfield, Department of Anatomical and Physiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53715, U.S.A.

    View full text