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Expression of Angiotensin Type-1 (AT1) and Type-2 (AT2) Receptor mRNAs in the Adult Rat Brain: A Functional Neuroanatomical Review,☆☆

https://doi.org/10.1006/frne.1997.0155Get rights and content

Abstract

The discovery that all components of the renin–angiotensin system (RAS) are present in the central nervous system led investigators to postulate the existence of a local brain RAS. Supporting this, angiotensin immunoreactive neurons have been visualized in the brain. Two major pathways were described: a forebrain pathway which connects circumventricular organs to the median preoptic nucleus, paraventricular nucleus, and supraoptic nucleus, and a second pathway connecting the hypothalamus to the medulla oblongata. Blood–brain barrier deficient circumventricular organs are rich in angiotensin II receptors. By activating these receptors, circulating angiotensin II may act on central cardiovascular centers via angiotensinergic neurons, providing a link between peripheral and central angiotensin II systems. Among the effector peptides of the brain RAS, angiotensin II and angiotensin III have the same affinity for the two pharmacologically well-defined receptors: type 1 (AT1) and type 2 (AT2). When injected in the brain, these peptides increase blood pressure, water intake, and anterior and posterior pituitary hormone release and may modify memory and learning. The cloning of AT1 and AT2 receptor cDNAs has revealed that these receptors belong to the seven transmembrane domain receptor family. In rodents, two AT1 receptor subtypes, AT1A and AT1B, have been isolated. Using specific riboprobes forin situhybridization histochemistry, recent studies mapped the distribution of AT1A, AT1B, and AT2 receptor mRNAs in the adult rat and found a predominant expression of AT1A and AT2 mRNA in the brain and of AT1B in the pituitary. Very limited overlap was found between the brain expression of AT1A and AT2 mRNAs. In several functional entities of the brain, such as the preoptic region, the hypothalamus, the olivocerebellary system, and the brainstem baroreflex arc, the colocalization of receptor mRNA, binding sites, and angiotensin immunoreactive nerve terminals suggests local synthesis and expression of angiotensin II receptors. In other areas, such as the bed nucleus of the stria terminalis, the median eminence, or certain parts of the nucleus of the solitary tract, angiotensin II receptors are likely of extrinsic origin. The neuronal expression of AT1A and AT2 receptors was demonstrated in the subfornical organ, the hypothalamus, and the lateral septum. By using double labelin situhybridization, AT1A receptor expression was localized in corticotropin releasing hormone but not in vasopressin containing neurons in the hypothalamus. The information is discussed together with functional data concerning the role of brain angiotensins, in an attempt to provide a better understanding of the physiological and functional roles of each receptor subtype.

References (244)

  • AT Chiu et al.

    Discrimination of angiotensin II receptor subtypes by dithiothreitol

    Eur J Pharmacol

    (1989)
  • S Conchon et al.

    Internalization of the rat AT1a and AT1b receptors: Pharmacological and functional requirements

    FEBS Lett

    (1994)
  • DI Diz et al.

    Contribution of the vagus nerve to angiotensin II binding sites in the canine medulla

    Brain Res Bull

    (1986)
  • TS Elton et al.

    Isolation of two distinct type I angiotensin II receptor genes

    Biochem Biophys Res Commun

    (1992)
  • AN Epstein

    Neurohormonal control of salt intake in the rat

    Brain Res Bull

    (1991)
  • AV Ferguson

    Neurophysiological analysis of mechanisms for subfornical organ and area postrema involvement in autonomic control

    Prog Brain Res

    (1992)
  • PP Feuillan et al.

    Angiotensin II binding sites in the rat fetus: characterization of receptor subtypes and interaction with guanyl nucleotides

    Regul Pept

    (1993)
  • H Furuta et al.

    Molecular cloning and sequencing of the gene encoding human angiotensin II type 1 receptor

    Biochem Biophys Res Commun

    (1992)
  • WF Ganong

    Blood, pituitary, and brain renin-angiotensin systems and regulation of secretion of anterior pituitary gland

    Front Neuroendocrinol

    (1993)
  • WF Ganong

    Reproduction and the renin-angiotensin system

    Neurosci Biobehav Rev

    (1995)
  • DR Gehlert et al.

    Autoradiographic localization of subtypes of angiotensin II antagonist binding in the rat brain

    Neuroscience

    (1991)
  • FJ Gordon et al.

    Electrical stimulation of the septal area in the rat: Prolonged suppression of water intake and correlation with self-stimulation

    Brain Res

    (1981)
  • DF Guo et al.

    The genomic organization of human angiotensin II type 1 receptor

    Biochem Biophys Res Commun

    (1994)
  • DF Guo et al.

    The genomic organization of the rat angiotensin II receptor AT1B

    Biochim Biophys Acta

    (1994)
  • DF Guo et al.

    The genomic organization of the rat angiotensin II receptor AT1B

    Biochim Biophys Acta

    (1994)
  • R Gyurko et al.

    Antisense inhibition of AT1 receptor mRNA and angiotensinogen mRNA in the brain of spontaneously hypertensive rats reduces hypertension of neurogenic origin

    Regul Pept

    (1993)
  • A WA Hahn et al.

    Identification of a fourth angiotensin AT1 receptor subtype in rat

    Biochem Biophys Res Commun

    (1993)
  • DC Hogarty et al.

    The role of angiotensin, AT1 and AT2 receptors in the pressor, drinking and vasopressin responses to central angiotensin

    Brain Res.

    (1992)
  • N Iwai et al.

    Identification of two subtypes in the rat type 1 angiotensin II receptor

    FEBS Letters

    (1992)
  • N Iwai et al.

    Differential regulation of rat AT1a and AT1b receptor mRNA

    Biochem Biophys Res Commun

    (1992)
  • N Iwai et al.

    Rat angiotensin II receptor: cDNA sequence and regulation of the gene expression

    Biochem Biophys Res Commun

    (1991)
  • AK Johnson

    The periventricular anteroventral third ventricle (AV3V): Its relationship with the subfornical organ and neural systems involved in maintaining body fluid homeostasis

    Brain Res Bull

    (1985)
  • AK Johnson et al.

    Integrative mechanisms and the maintenance of cardiovascular and body fluid homeostasis: The central processing of sensory input derived from the circumventricular organs of the lamina terminalis

    Prog Brain Res

    (1992)
  • G Aguilera et al.

    Angiotensin II receptors and prolactin release in pituitary lactotrophs

    Endocrinology

    (1982)
  • G Aguilera et al.

    Increased expression of type 1 angiotensin II receptors in the hypothalamic paraventricular nucleus following stress and glucocorticoid administration

    J Neuroendocrinol

    (1995)
  • G Aguilera et al.

    Angiotensin II receptors: Properties and regulation in adrenal glomerulosa cells

    Circ Res

    (1980)
  • G Aguilera et al.

    Direct regulation of hypothalamic corticotropin-releasing-hormone neurons by angiotensin II

    Neuroendocrinology

    (1995)
  • AM Allen et al.

    Angiotensin receptors and the vagal system

    Clin Exp Hypertens [A]

    (1988)
  • AM Allen et al.

    Angiotensin II receptor binding and the baroreflex pathway

    Clin Exp Hypertens

    (1988)
  • AM Allen et al.

    Localization of angiotensin receptor binding sites in the rat brain

    Handbook of Chemical Neuroanatomy: Vol. 11, Neuropeptide Receptors in the CNS

    (1992)
  • AM Allen et al.

    Actions of angiotensin II in the ventrolateral medulla oblongata

    Central Neural Mech Cardiovasc Regul

    (1991)
  • AJ Balmforth et al.

    Comparative pharmacology of recombinant rat AT1A1B1

    Brit J Pharmacol

    (1994)
  • W Bargmann et al.

    The site of origin of the hormones of the posterior pituitary

    Am Sci

    (1951)
  • J Barry et al.

    LHRH-containing systems

  • N Bouby et al.

    Type 1 angiotensin II receptor subtypes in kidney of normal and salt-sensitive hypertensive rats

    Hypertension

    (1996)
  • CR Brandt et al.

    Renin mRNA is synthesized locally in rat ocular tissues

    Curr Eye Res

    (1994)
  • J Buggy et al.

    Preoptic–hypothalamic periventricular lesions: Thirst deficits and hypernatremia

    Am J Physiol

    (1977)
  • FM Bumpus et al.

    Nomenclature for angiotensin receptors. A report of the Nomenclature Committee of the Council for High Blood Pressure Research

    Hypertension

    (1991)
  • R Casto et al.

    Cardiovascular actions of microinjections of angiotensin II in the brain stem of rats

    Am J Physiol

    (1984)
  • E Castren et al.

    Repeated stress increases the density of angiotensin II binding sites in rat paraventricular nucleus and subfornical organ

    Endocrinology

    (1988)
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    Address correspondence and reprint requests to C. Llorens-Cortès, INSERM U36, Chaire de Médecine Expérimentale, Collège de France, 75005 Paris, France, Fax: (33-1) 44-27-16-91, E-mail: [email protected].

    ☆☆

    A, BjörklundT, HökfeltM, J, Kuhar, Eds.

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