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

Brownfield, Mark S.; Reid, Ian A.; Ganten, Detlev; Ganong, William F.

doi:10.1016/0306-4522(82)90033-1

Cited by 173 publications

(73 citation statements)

References 28 publications

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“…Brownfield et al (71) have attempted to reconcile these conflicting immunohistochemical findings in experiments in which 12 different All antisera were used. Staining was found with only 3 of the antisera and this All immunoreactivity was confined to neural elements of the rat brain, including neuronal perikarya in the paraventricular, supraoptic, and accessory magnocellular nuclei and the medial part of the suprachiasmatic nucleus and nerve terminals in the median eminence, neurohypophysis, central nucleus of the amygdala, bed nucleus of the stria terminals, intermediolateral column, and substantia gelatinosa of the spinal cord, and the trigeminal spinal nucleus.…”

Section: Discussionmentioning

confidence: 99%

Autoradiographic localization of angiotensin II receptors in rat brain.

Mendelsohn¹,

Quirion²,

Saavedra³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

442

209

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The 125I-labeled agonist analog [1-sarcosine]-angiotensin II ([Sar']AII) bound with high specificity and affinity (Ka = 2 x 109 M-1) to a single class of receptor sites in rat brain. This ligand was used to analyze the distribution of All receptors in rat brain by in vitro autoradiography followed by computerized densitometry and color coding. A very high density of All 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, preand 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 All receptors are distributed in a highly characteristic anatomical pattern in the brain. The high concentrations of All receptors at numerous physiologically relevant sites are consistent with the emerging evidence for multiple roles of All as a neuropeptide in the central nervous system.

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Section: Discussionmentioning

confidence: 99%

Autoradiographic localization of angiotensin II receptors in rat brain.

Mendelsohn¹,

Quirion²,

Saavedra³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

442

209

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“…A II-like immunoreactivity has been demonstrated in the rat pituitary (2,8,24). However, the precise nature of the A II-immunoreactive material and its origin were not definitively established.…”

Section: Discussionmentioning

confidence: 99%

“…(8) and later by Brownfield er al. (2) and Steele er al. (24), yielding conflicting results regarding the presence of positive staining in pars intermedia and pars nervosa; Steele er a1.…”

mentioning

confidence: 94%

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<b>CO-LOCALIZATION OF ANGIOTENSIN II AND RENIN IN GROWTH HORMONE-CONTAINING CELLS OF THE BOVINE </b><b>PITUITARY </b>

Hirose¹,

Yamamoto²,

KANAZAWA³

et al. 1985

Biomed. Res.

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Co-localization ofangiotensin II (A II) and renin in the growth hormone (GH)-containing cells of the bovine pituitary has been immunohistochemically demonstrated. A II has recently been shown to be present in the pituitary and involved in the regulation of secretion of pituitary hormones in addition to the classical physiological functions in the general circulation. To identify A II-producing cells, sections of the bovine pituitary were stained for the presence ofA II and renin, an enzyme responsible for the formation of A II, using the avidin-biotin-peroxidase complex method. Anti-A II revealed a widespread distribution ofmoderately stained cells. Most ofthese A II-positive cells were also stained with an antirenin antibody although the staining was less intense than with anti-A II. Furthermore, co-localization studies indicated that the majority ofA II-and reninstained cells were GH-immunoreactive. These results provide visual evidence for the intracellular formation of A II in the bovine pituitary where it helps to coordinate the secretion of other hormones.Angiotensin II (A II), an octapeptide, is the most powerful pressor substance and a potent stimulus for the aldosterone secretion (l9). In addition to these well-known peripheral actions, A II has still other important functions. In the pituitary, it stimulates ACTH and LH release and depresses GH and prolactin secretion (7, 20, 23, 25, 26). In support of the contention that A II can influence pituitary function, specific receptors for A II have been reported to occur in the pituitaries of the rat (9, 10, 21), mouse (9, I0), hamster (9), rabbit (10) and dog (10) and on cultured rat pituitary cells (1, 3, 18). Renin, an aspartyl proteinase responsible for the generation of A II, has also been demonstrated in the pituitary by biochemical (1 l, 12) and immunohistochemical studies (4, 14, 22), suggesting that angiotensin II is produced within the pituitary. Knowledge of the precise cellular location of A II within the pituitary would contribute to a better understanding of its roles in regulating the secretion of the pituitary hormones.Immunohistochemical demonstration of A II in the pituitary was first attempted by Ganten er al. (8) (24) have shown that angiotensin-like immunoreactivity is limited only to pars distalis and codistributed with LH, FSH, and prolactin. Furthermore, staining could be demonstrable with only three antisera, raised by Ganten and his coworkers and characterized by Brownfield er al. (2), against A II conjugated with glutaraldehyde to bovine serum albumin; many other antisera, though excellent for purposes of radioimmunoassay, failed to stain (2).In the present study, therefore, we raised new stainable antisera in rabbit by immunizing A II coupled to thyroglobulin with ethyl-3-(3-dimethylaminopropyl)-carbodiimide and exam-

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“…Ganten et al (4) isolated angiotensin I and A N G II from the rat brain and demonstrated the central nature of ANG I1 production by the intracerebroventricular administration of an inhibitor of angiotensin-converting enzyme which caused a reduction in local ANG 11. Furthermore, the presence of each of the components of the renin angiotensin system (RAS) has been demonstrated immunocytochemically (5)(6)(7)(8) and the likelihood of local production supported by the identification of mRNA for renin and angiotensinogen (9,10). However, the cellular disposition of each of the components of the RAS still remains unclear, as does the nature of their interaction and the degree of their anatomical overlap.…”

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confidence: 99%

An Ultrastructural Analysis of the Distribution of Angiotensin II in the Rat Brain

Oldfield

Ganten

1989

J Neuroendocrinology

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Abstractlmmunopositive angiotensin I1 nerve fibres and terminals are widely distributed throughout the rat brain, including areas of the brain with and without a blood-brain barrier. Ultrastructural examination indicates that in the circumventricular organs (areas which lack a blood-brain barrier), many angiotensin Il-positive nerve terminals are closely aligned with fenestrated blood vessels and do not have synaptic specializations. This appearance is in contrast to that of angiotensin II terminals in regions with a blood-brain barrier where there exists a more typical synaptic configuration. In both cases, angiotensin II is contained within large (100 to 125 nm) vesicles which coexist with smaller, lucent, non-immunoreactive vesicles. These observations suggest a possible duality of function such that angiotensin II in circumventricular organs may be secreted into the circulation, whereas angiotensin I I in the remainder of the brain is more likely to be acting as a neurotransmitter or neuromodulator.The octapeptide, angiotensin 11 (ANG II), when administered into the CNS, causes a number of well-defined physiological and behavioural responses including thirst, vasopressin secretion, natriuresis, increased blood pressure and salt appetite (1-3).One of the major questions central to understanding the actions of ANG I1 in the brain has been the source of its production. Ganten et al. (4) isolated angiotensin I and A N G II from the rat brain and demonstrated the central nature of ANG I1 production by the intracerebroventricular administration of an inhibitor of angiotensin-converting enzyme which caused a reduction in local ANG 11. Furthermore, the presence of each of the components of the renin angiotensin system (RAS) has been demonstrated immunocytochemically (5-8) and the likelihood of local production supported by the identification of mRNA for renin and angiotensinogen (9, 10). However, the cellular disposition of each of the components of the RAS still remains unclear, as does the nature of their interaction and the degree of their anatomical overlap. Immunocytochemically-identified A N G I1 is contained in a network of neural pathways connecting areas of the forebrain and brainstem which are largely concerned with autonomic or homeostatic functions (11). It is on the basis of these studies and the good correlation of A N G 11-positive terminal fields with A N G II receptors (12-15) that ANG I1 is suggested to act as a neurotransmitter/neuromodulator in the CNS.The present study has sought to further elucidate the action of ANG 11 in the CNS by examining its ultrastructural distribution. In particular, we have focused on the nature of morphological interactions between A N G 11-positive elements and other neural and non-neural structures in a range of brain areas.Previous studies at the light microscopic (LM) level have shown ANG 11-positive structures, presumed to be terminals, to be aggregated both in circumventricular organs (CVOs) and in regions behind the blood-brain barrier. Because the function of ...

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

Cited by 173 publications

References 28 publications

Autoradiographic localization of angiotensin II receptors in rat brain.

Autoradiographic localization of angiotensin II receptors in rat brain.

<b>CO-LOCALIZATION OF ANGIOTENSIN II AND RENIN IN GROWTH HORMONE-CONTAINING CELLS OF THE BOVINE </b><b>PITUITARY </b>

An Ultrastructural Analysis of the Distribution of Angiotensin II in the Rat Brain

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