Increased dithiothreitol-insensitive, type 2 angiotensin II receptors in selected brain areas of young rats (original) (raw)
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Developmental changes in brain angiotensin II receptors in the rat
Peptides, 1991
MILLAN, M. A., A. KISS AND G. AGUILERA. Developmental changes in brain angiotensin H receptors in the rat. PEP-TIDES 12(4) 723-737, 1991.--AII binding and distribution were measured in rat brain during development by autoradiographic techniques using radioiodinated [Sarl,IleS]AII. At all ages, from 2 days to 7 weeks, binding was present in the circumventricular organs, and areas related to pituitary hormone secretion and modulation of sympathetic activity. At early stages of development, AII binding was transiently expressed in a number of motor-and sensory-related areas. These findings support a role for AI1 in the control of water intake and autonomic activity at all stages of development, and suggest that the peptide may be involved in the maturation of neuronal function during development.
Characterization and development of angiotensin II receptor subtypes (AT1 and AT2) in rat brain
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1991
Characterization and development of angiotensin II receptor subtypes (AT1 and AT,) in rat brain. Am. J. Physiol. 261 (Regulatory Integrative Comp. Physiol. 30): R209-R216, 1991.-Angiotensin II receptor subtypes (AT1 and AT,) were characterized in rat brain by displacement with the specific angiotensin antagonists Du Pont 753 and CGP 42112A, respectively, and quantitative autoradiography. Young (2-wk-old) rats expressed AT1 receptors in selected limbic system areas, structures involved in cardiovascular and fluid regulation, parts of the hippocampal formation, and the choroid plexus. In young rats, AT, receptors were concentrated in areas involved in control and learning of motor activity, sensory areas, and selected limbic system structures. The cingulate cortex, the molecular layer of the cerebellar cortex, and the superior colliculus contained both ATI and AT, receptors. The number of ATI receptors in most areas of adult (&wk-old) rats was similar to or even higher than that present in young rats. Conversely, AT, receptors were always much lower in number in adult animals, and in some areas they were undetectable in adults. Their differential localization and development suggest different functions for the specific angiotensin II receptor subtypes. angiotensin receptor subtypes; Du Pont 753; CGP 42112A; renin-angiotensin system; receptor development IN ADULT RATS, the brain angiotensin II (ANG II) system, including specific ANG II receptors located in very select areas, is involved in the central regulation of cardiovascular function, drinking and fluid metabolism, salt appetite, vasopressin release, and stress (4, 5, 13, 14, 21, 23, 24). Peripherally formed ANG II, present in the has been proposed on the basis of the response of smooth muscle to ANG II synthetic analogues (19). More recently, terized two subtypes in peripheral of ANG II receptors were charactissues on the basis of their sensitivity to reducing agents (7, 10-12) and their displacement with newly developed specific ANG II antagonists (6, 8, 9, 30). AT, receptors are sensitive to the reducing agent dithiothreitol (DTT) (7,9-12) and to displacement by the selective ANG II antagonist Du Pont 753 (8, 9). ANG II binding to the AT, receptors is resistant to DTT and selectively displaced by the ANG II-receptor antagonist CGP 42112A (30). Q uantitative autoradiography and displacement with the selective ANG II-receptor antagonists revealed that the rat brain contains AT1 receptors lot ular nucleus ated in the s , nucleus of ubfornical organ, pa the solitary tract, raven and tricarea postrema and AT, receptors localized in the inferior olive (27). The characteristics of the brain AT1 and AT2 receptors was similar to those described in peripheral organs (27). We have in the inferior recently shown by autoradiography that, olive, parasolitary and hypoglossal nuclei, and cerebellar cortex, the brain of young rats expresses more ANG II receptors than that of adult animals (28) and that, in the inferior olive of young and adult rats, the binding is insensitive to DTT (29). These observations suggested that young rats may express more AT, receptors than their adult controls. To determine the detailed developmental pattern of the receptor subtypes throughout the brain, we studied all areas containing significant numbers of ANG II receptors and compared their distribution and sensitivity to selected ANG II general circulation, binds to brain ANG II receptors antagonists in young (2-wk-o located in circumventricular organs outside the blood-rats. brain barrier (16, 21, 22) and contributes to the central regulation of cardiovascular function and fluid homeo-MATERIALS AND METHODS
European Journal of Pharmacology: Molecular Pharmacology, 1992
We studied the effect of the sulfhydryl reducing agent dithiothreitol on the binding of the angiotensin II agonist [12Sl][Sar~]-angiotensin II to A'i-. receptors in sclectcd brain areas of young (2-week-old) rats. In the inferier olive and the hypoglossal nucleus, angiotensin !I binding to AT, receptors was insensitive 1o 5 mM dithiothrcitol. Conversciy, in the ventral and mediodersal thalamic, mcdial gcniculate, and oculomotor nuclei, the superior colliculus and the ccrebellar cortex, incubatkm with 5 mM dithiothreitol significantly decreased angiotcnsin 11 binding to ATe. receptors to about ae.e,.,j :c of control. These data
Brain Research, 1990
The effect of a 4-week period of selective dietary sodium depletion on the regulation of peripheral and central angiotensin II receptors was studied in young rats, by quantitative autoradiography. Moderate sodium depletion (0.05% sodium in diet) significantly impaired growth rate and stimulated the renin-angiotensin system, but did not result in significant changes in peripheral or central angiotensin II receptors. In young rats, the impairment of the growth rate and the stimulation of the peripheral renin-angiotensin system were more notable after profound sodium depletion (0.005% sodium in diet). Such sodium depletion corresponded to a down-regulation of kidney angiotensin II receptors, and to an up-regulation of adrenal zona glomerulosa angiotensin II receptors. These effects are similar to those reported in adult rats. In the brain, profound sodium depletion down-regulated angiotensin II receptors in the subfornical organ. There were no changes in angiotensin II receptors in another brain structure, the paraventricular nucleus. Our results indicate a participation of selective central angiotensin II receptors in the regulation of sodium metabolism and suggest that factors other than circulating angiotensin II levels might contribute to regulate the number of angiotensin II receptors in the subfornical organ.
Pediatric Research, 1999
Studies have demonstrated a specific function of the angiotensin II (Ang II) type 1 receptor (AT 1 ) in regulation of adult central cardiovascular, fluid, and pituitary hormone release and a predominant role of the renin-angiotensin system in fetal and neonatal cardiovascular homeostasis. The pattern of brain AT 1 mRNA expression during fetal and neonatal development is currently unknown. We used radiolabeled cRNA probes for in situ hybridization histochemistry to determine the ontogenic development of the two AT 1 subtypes (AT 1a and AT 1b ) mRNA in rat brain, from 11 days of gestation (E11) to 28 days after birth (P28). No AT 1b mRNA was detected in the developing brain, whereas AT 1a mRNA was first detected at E19. The age at which AT 1a mRNA is first detected varied among different brain areas and expression predominates in areas involved in fluid homeostasis, pituitary hormone release, and cardiovascular regulation, where it persists until P28. AT 1a mRNA expression is present from E19 onward in the median preoptic nucleus, the vascular organ of the lamina terminalis, the paraventricular nucleus, the periaqueductal gray, the nucleus raphe pallidus, the motor facial nucleus, and very weakly in the nucleus of the solitary tract and the ambiguus nucleus, and at E21 in the subfornical organ, the anterior olfactory nucleus and the piriform cortex. AT 1a mRNA expression is present after birth in many regions, including the preoptic and lateral hypothalamic areas, the area postrema and medullary reticular nuclei. In conclusion, during brain development, expression of AT 1a mRNA, appears in late gestation at E19, predominantly in forebrain areas involved in fluid homeostasis and cardiovascular regulation. In contrast, AT 1a mRNA expression is absent or present only in very small amounts until after birth in many medullary nuclei, known to play an important role in cardiovascular modulation. Our results suggest that, in perinatal life, AT 1a is involved in fluid and perhaps cardiovascular homeostasis and that the role of Ang II in modulating medullary cardiovascular centers matures later in postnatal life.
Angiotensin II receptor subtypes and angiotensin-converting enzyme in the fetal rat brain
Brain Research, 1993
Angiotensin II (ANG II) receptor subtypes (AT l, displaced by losartan, and AT 2, displaced by CGP 42112A) were characterized by quantitative autoradiography after incubation with the ANG If agonist [lzSI]SarLANG II, in specific brain nuclei of 19-day-old rat embryos. Binding to AT 1 receptors, located in the subfornical organ, paraventricular nucleus, nucleus of the solitary tract and choroid plexus, was sensitive to incubation with GTPyS. The sensitivity of AT z receptors to GTPyS was heterogeneous. In the ventral thalamic, rostral hypoglossal and medial genicutate nuclei, and in the locus coeruleus, binding to AT 2 receptors was sensitive to GTPyS and these areas belong to the AT2A subgroup. Conversely, in the inferior olive, medial (fastigial) cerebellar nucleus and caudal part of the hypoglossal nucleus, areas belonging to the AT2B subgroup, binding was insensitive to GTPyS. AT 2 receptors were also present in cerebral arteries. In the fetal anterior pituitary, AT t receptors .... i25 In predominated. The angiotensin-converting enzyme (ACE; EC 3.4.15.1) was studied by autoradiography with the selectwe inhibitor [ I]35 tA. 19-day-old embryos, ACE was highly expressed in choroid plexus, with high concentrations in subfornical organ, posterior pituitary and cerebral arteries. No ACE binding was detected in extrapyramidal structures or anterior pituitary in 19-day-old embryos.
Angiotensin II Receptor Subtypes in Rat Brain
Clinical and Experimental Pharmacology and Physiology, 1991
1. Angiotensin I1 (AII) receptor binding was localized in the rat brain by in vitro autoradiography using the antagonist analogue, 1251-[Sar1,11e8] AII. A11 receptor binding was then differentiated into type I and type I1 subtypes by displacement with unlabelled non-peptide antagonists specific for A11 subtypes. 2. Type I binding was determined as that inhibited by Dup753 (10 pmol/L) and type I1 binding as that inhibited by XD329-1 (10 pmol/ L). The reducing agent dithiothreitol (DTT) decreased the binding to type I receptors and enhanced the binding to type I1 receptors. 3. Structures such as the vascular organ of the lamina terminalis, subfornical organ, median preoptic nucleus, area postrema, nucleus of the solitary tract, which are known to be related to some central actions of AII, contain exclusively type I A11 receptors. 4. In contrast, the locus coeruleus, ventral and dorsal parts of lateral septum, superior colliculus, subthalamic nucleus, some nuclei of the thalamus, and the nuclei of the inferior olive contain predominantly type I1 A11 receptors. 5. These results reveal important pharmacological heterogeneity of brain A11 receptors which suggest different regional functions and are relevant to the central actions of emerging classes of new non-peptide A11 receptor antagonists.
Experimental Neurology, 1990
Levels of immunoreactive angiotensin II (ANG II) were measured in specific microdissected nuclei from the brains of newborn (NB; less than 1 week of age), 4-, 8, and la-week-old spontaneously hypertensive rats (SHR) and their age-matched normotensive controls, Wistar Kyoto (WKY) rats, using a sensitive radioimmunoassay. The structures investigated included the paraventricular nucleus of the hypothalamus (PVH), the nucleus of the solitary tract (NTS), the dorsal motor nucleus of the vagus (DMN of X), the locus coeruleus (LC), and the Al region of the medulla. A section of cerebellar cortex was used as a control. Although ANG II was detected in each of the nuclei examined, there were no differences in the ANG II contents of any of these structures between young (NB and 4 week old) SH and WKY rats. However, by 8 weeks of age, the SHR had significantly higher ANG II levels in the PVH, NTS, and DMN of X than its normotensive control, and at 12 weeks of age, significantly higher ANG II levels were observed in the PVH, NTS, DMN of X, and LC of the SHR compared to those in the WKY. During the developmental period under investigation, both strains revealed increases in the ANG II content of all nuclei except for the LC, where the ANG II levels decreased with age. No detectable ANG II was found in the cerebellar cortex of either strain at any age. Since the brain and brain stem nuclei examined in this investigation have been implicated in the neural control of cardiovascular function, we conclude that the differences in ANG II levels between SH and WKY rats during development support the postulated role for ANG II in the pathogenesis of hypertension in the SH rat model. o 1990 Academic PWS, IUC.
The distribution of angiotensin II binding sites in rodent brain
Brain Research, 1981
The distribution of specific angiotensin II (AII) binding capacity of several brain regions, pituitary, and adrenals was determined in 6 rodent species namely rats, mice, hamsters, kangaroo rats, gerbils and degus. Rats and mice had similar distributions with the highest levels of ...