Angiotensin II receptor localization in the canine CNS

doi:10.1016/0006-8993(85)91392-7

Brain Research

Volume 326, Issue 1, 4 February 1985, Pages 137-143

https://doi.org/10.1016/0006-8993(85)91392-7 Get rights and content

Abstract

Specific binding of [¹²⁵I]angiotensin II ([¹²⁵I]Ang II) to sections of dog brain was determined by in vitro receptor autoradiography. Highly discrete, dark images representing specific binding of [¹²⁵I]Ang II were observed in areas corresponding to the nucleus of the solitary tract, dorsal motor nucleus of the vagus, area postrema, ventrolateral medulla, pineal, subfornical organ, nucleus medianus, septum, organum vasculosum of the lamina terminalis and the anterior pituitary. The specific binding was frequently present either as a narrow band or tiny spot within a small portion of the nuclei to which the binding corresponded. The location of these Ang II recognition sites in regions associated with regulation of autonomic and neuroendocrine function provides further evidence for a role of this peptide within the central nervous system.

Reference (29)

BennettJ.P. et al.
Angiotensin II binding to mammalian brain membranes
J. biol. Chem.
(1976)
ColeF.E. et al.
Angiotensin binding affinity and capacity in the midbrain area of spontaneously hypertensive and normotensive rats
Brain Research
(1978)
FuxeK. et al.
Immunohistochemical evidence for the existence of angiotensin II containing nerve terminals in the brain and spinal cord of the rat
Neurosci. Lett.
(1976)
GehlertD.R. et al.
Autoradiographic localization of angiotensin II receptors in the rat brain and kidney
Europ. J. Pharmacol.
(1984)
GehlertD.R. et al.
Autoradiographic localization of angiotensin II receptors in the rat brainstem
Life Sci.
(1984)
HardingJ.W. et al.
The distribution of angiotensin II binding sites in rodent brain
Brain Research
(1981)
HuwylerT. et al.
Angiotensin II sensitive neurons in septal areas of the rat
Brain Research
(1980)
SinghR. et al.
Rat brain angiotensin II receptors: effects of intraventricular angiotensin II infusion
Brain Research
(1984)
StamlerJ.F. et al.
Increased specific binding of angiotensin II in the organum vasculosum of the laminae terminalis area of the spontaneously hypertensive rat brain
Neurosci. Lett.
(1980)
Van HoutenM. et al.
Radioautographic localization of specific binding sites for blood-borne angiotensin II in the rat brain
Brain Research
(1980)

BurtD.R.

Other peptide receptors

ChangarisD.G. et al.

Localization of angiotensin in rat brain

J. Histochem. Cytochem.

(1978)

ChenF.M. et al.

Evidence for a functional, independent brain-angiotensin system: correlation between regional distribution of brain angiotensin receptors, brain angiotensinogen and drinking during the estrous cycle of rats

FerrarioC.M. et al.

Cardiovascular effects of angiotensin mediated by the central nervous system

Circulat. Res.

(1972)

Cited by (97)

Cognitive benefits of angiotensin IV and angiotensin-(1–7): A systematic review of experimental studies
2018, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
Additionally, Ang IV is known to mediate central pressor effects through binding to the AT1R (Yang et al., 2008); hence, some of its cognitive effects may involve this receptor type as well. However, there is little research in this area, given the much higher affinity of Ang IV for AT4R as opposed to AT1R (Speth et al., 1985). It has also been proposed that IRAP, the binding site of AT4R, may not be the only one site mediating Ang IV effects.
To explore effects of the brain renin-angiotensin system (RAS) on cognition.
Systematic review of experimental (non-human) studies assessing cognitive effects of RAS peptides angiotensin-(3–8) [Ang IV] and angiotensin-(1–7) [Ang-(1–7)] and their receptors, the Ang IV receptor (AT4R) and the Mas receptor.
Of 450 articles identified, 32 met inclusion criteria. Seven of 11 studies of normal animals found Ang IV had beneficial effects on tests of passive or conditioned avoidance and object recognition. In models of cognitive deficit, eight of nine studies found Ang IV and its analogs (Nle¹-Ang IV, dihexa, LVV-hemorphin-7) improved performance on spatial working memory and passive avoidance tasks. Two of three studies examining Ang-(1–7) found it benefited memory. Mas receptor removal was associated with reduced fear memory in one study.
Studies of cognitive impairment show salutary effects of acute administration of Ang IV and its analogs, as well as AT4R activation. Brain RAS peptides appear most effective administered intracerebroventricularly, close to the time of learning acquisition or retention testing. Ang-(1–7) shows anti-dementia qualities.
Circumventricular Organs
2012, The Human Nervous System, Third Edition
Endogenous kappa opioids mediate the action of brain angiotensin II to increase blood pressure
2007, Neuropeptides
The objectives of this study were to determine whether endogenous opioids are operative in modulating the CNS action of angiotensin II (ang II) on blood pressure and to determine whether this is mediated by endogenous mu or kappa opioid receptor agonists.
The study design was: unanesthetized Wistar rats, 300–400 g, previously instrumented with a cannula in the lateral cerebral ventricle and a catheter in the femoral artery, had ang II, 0.5 μg, injected into the lateral cerebral ventricle (ICV). Groups were allocated to receive naloxone, a mu opioid receptor antagonist or MR 2266 a selective kappa opioid receptor antagonist prior to ang II. In other experiments in unanesthetized rats, baroreceptor reflex function was assessed by intravenous injection of phenylephrine or nitroprusside and the interaction of endogenous opioids and ang II ascertained with use of the mu or kappa opioid receptor antagonist .
Ang II significantly (p < 0.05) increased systolic and diastolic blood pressure. The kappa opioid antagonist, MR 2266, 25 μg/kg ICV, significantly (p < 0.05) reduced and MR 2266, 50 μg/kg ICV, completely prevented the increase in blood pressure produced by ang II. In contrast, the mu opioid receptor antagonist, naloxone, 50 μg/kg, ICV, did not significantly attenuate the blood pressure responses to ang II. Ang II induced alteration in baroreceptor function. The effect of ang II on baroreceptor function was significantly antagonized by the kappa opioid receptor antagonist MR 2266.
In conclusion, these data indicate that: (a) endogenous opioids modulate the pressor response to intracerebral ang II, (b) this effect is mediated mainly through endogenous kappa opioid agonists and kappa rather than mu opioid receptors, (c) alteration of baroreceptor sensitivity by ang II is modulated by endogenous kappa opioids.
Enzymatic pathways of the brain renin-angiotensin system: Unsolved problems and continuing challenges
2007, Regulatory Peptides
Circumventricular Organs
2003, The Human Nervous System: Second Edition
Chapter iii Localization of angiotensin receptors in the nervous system
2000, Handbook of Chemical Neuroanatomy
This chapter demonstrates that angiotensin receptors occur in a characteristic distribution throughout the central nervous system. A very high degree of overlap exists between the distributions of AT₁ receptor binding sites, AT₁ receptor mRNA and AT₁ receptor immunoreactivity. In addition, a high correlation exists between the distributions of AT₂ receptor mRNA and AT₂ receptor binding sites. In general the AT₁ receptors occur in regions associated with regulation of fluid and electrolyte homeostasis, neuroendocrine control and autonomic regulation of the cardiovascular system. However, the distribution of AT₁ receptors is much more widespread suggesting that angiotensin may play a much wider role in the central nervous system. The distribution of AT₂ receptors in the thalamic nuclei of the rat brain and also AT₁ and AT₂ receptors in many other sensory-associated nuclei also suggest additional, currently undefined actions in these regions. It is of interest to note that the AT₂ receptor distribution varies considerably between the species studied. In contrast, the AT₁ receptor distribution is highly conserved between species, including the human, indicating that physiological studies on AT₁ receptor function in experimental animals will probably have considerable relevance in understanding human physiology and pathophysiology.

View all citing articles on Scopus

View full text

Angiotensin II receptor localization in the canine CNS

Abstract

J. biol. Chem.

Brain Research

Neurosci. Lett.

Europ. J. Pharmacol.

Life Sci.

Brain Research

Brain Research

Brain Research

Neurosci. Lett.

Brain Research

Other peptide receptors

Localization of angiotensin in rat brain

J. Histochem. Cytochem.

Evidence for a functional, independent brain-angiotensin system: correlation between regional distribution of brain angiotensin receptors, brain angiotensinogen and drinking during the estrous cycle of rats

Cardiovascular effects of angiotensin mediated by the central nervous system

Circulat. Res.