Radioautographic Localization of &lt;sup&gt;125&lt;/sup&gt;I-Atrial Natriuretic Factor Binding Sites in the Brain

Bianchi, C; Gutkowska, Jolanta; Ballak, M.; Thibault, G; García, Raúl; Genest, J; Cantin, M.

doi:10.1159/000124670

Cited by 55 publications

(11 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Brain tissue reportedly contains many ANP-specific receptors involved in the regulation of guanylyl cyclase. 24,25 ANP has been shown to raise intracellular cGMP levels in cultured astroglia, 10 suggesting that ANP prevents the swelling of astroglia in brain tissue through the regulation of sodium transport. After high salt loading, sodium influx from the blood to the brain across the blood-brain barrier may therefore be interrupted by ANP.…”

Section: Discussionmentioning

confidence: 99%

Atrial Natriuretic Peptide Gene Delivery Reduces Stroke-Induced Mortality Rate in Dahl Salt-Sensitive Rats

Lin

Chao

1999

Hypertension

View full text Add to dashboard Cite

Abstract-Atrial natriuretic peptide (ANP) is a powerful hormone with hypotensive, natriuretic, diuretic, and many other beneficial effects. Direct infusion of ANP in therapeutics has limited success because of its short half-life in the circulation. Our previous studies have shown that ANP gene delivery attenuates hypertension, cardiac hypertrophy, and renal injury in Dahl salt-sensitive (Dahl-SS) rats. To investigate the potential therapeutic value of ANP gene delivery on salt-induced stroke and cerebrovascular disorders, an adenovirus harboring the human ANP gene (Ad.RSV-cANP) was injected into Dahl-SS rats on a high salt diet. A single intravenous injection of the ANP gene caused a significant reduction of blood pressure that lasted for more than 3 weeks. A maximal blood pressure reduction of 28 mm Hg was observed 2 weeks after gene delivery as compared with that of control rats injected with adenovirus harboring the LacZ gene under the control of the Rous sarcoma virus promoter (Ad.RSV-LacZ). Immunoreactive human ANP can be detected in the heart, lung, kidney, and brain of rats after gene delivery. The stroke mortality rate of Dahl-SS rats was significantly decreased (from 54% to 17% at 3 weeks and from 70% to 50% at 4 weeks after ANP gene delivery as compared with rats injected with control virus). ANP gene delivery also significantly attenuates salt-induced aortic hypertrophy as evidenced by reduced thickness of the aortic wall. This is the first study to demonstrate the potential of ANP gene delivery in reducing the mortality rate caused by cerebrovascular disorders and stroke.

show abstract

Section: Discussionmentioning

confidence: 99%

Atrial Natriuretic Peptide Gene Delivery Reduces Stroke-Induced Mortality Rate in Dahl Salt-Sensitive Rats

Lin

Chao

1999

Hypertension

View full text Add to dashboard Cite

show abstract

“…Previous data [1] reported the presence of ANF binding sites in ChP on epithelial cells and capillary endothelium, as ana lyzed by in vivo autoradiography at the light-microscopic level.…”

Section: Discussionmentioning

confidence: 82%

“…The tight junctions constitute the blood-CSF barrier at the level of ChP [ 17], Several lines of evidence suggest that atrial natriuretic factor (ANF) influences the function of ChP. ANF binding sites have been detected in ChP by autoradiography in vitro [28,31] and by light-microscopic autoradiography in vivo [ 1 ], and they have been characterized by quantitative autoradiography in vitro [22,23,30], It has been demonstrated that in ChP ANF stimulates guanylate cyclase activity [13,34] and increases cGMP levels [37], ANF significantly decreases the rate of CSF formation when injected into the cerebral ventricles [34], Although ANF receptors have been localized to choroidal epithelial cells in culture (by demonstration of stimulation of guanylate cyclase by ANF) [34], the precise cellular localization of the ANF binding sites has never been demonstrated in the intact ChP. We have approached this problem, in the present studies, by applying the technique of electron-microscopic autoradiography in vivo using 1251-ANF (Ser 99-Tyr 126) as an in vivo ligand.…”

mentioning

confidence: 99%

Localization and Characterization of Binding Sites for Circulating and Cerebroventricular Atrial Natriuretic Factor in Rat Choroid Plexus

Konrad¹,

Bianchi²,

Thibault³

et al. 1990

Neuroendocrinology

Self Cite

View full text Add to dashboard Cite

In vitro autoradiographic studies showed that high-affinity atrial natriuretic factor (ANF) binding sites are present on rat choroid plexus (Kd = 83.8 pM, B_max = 22.9 fmol/mg protein). Guanylate cyclase-coupled receptors (ANF-Ri) represent 30% and non-guanylate cyclase-coupled ANF receptors (ANF-R2) represent 70% of the total ANF receptors present in this tissue. To provide detailed cellular localization of the binding sites, the technique of electron-microscopic autoradiography was applied using ^l25I-ANF (Ser 99-Tyr 126) as an in vivo ligand. In order to identify possible binding sites at the basolateral and the apical aspects of the choroid plexus, the ligand was injected into the carotid artery or into the lateral cerebral ventricles, respectively. Light-microscopic autoradiography demonstrated that ANF binds specifically to choroid plexus regardless of its route of administration. Electron-microscopic autoradiography showed that silver grains were localized primarily on epithelial cells of the choroid plexus (96–99%) and marginally on endothelial and pial cells. In choroidal epithelial cells, ultrastructural analysis of silver grain distribution revealed that, at 2 min after intracarotid or intracerebroventricular ¹²⁵I-ANF injection, lysosomes were the most distinctly labeled organelle (highest relative specific radioactivity). HPLC Chromatographic analysis disclosed that 96–99% of choroid plexus-bound ANF was already degraded 2 min after injection and that at least 63–66% of the degradation took place at the plasma membrane. These results indicate that ANF binding sites are present on both aspects of choroidal epithelium, and suggest that ANF is very quickly degraded in choroid plexus by membrane-associated as well as lysosome-associated processes.

show abstract

“…The elevation of intracellular cGMP levels by guanylate cyclase is considered to mediate this. Brain tissue reportedly contains many ANP-specific receptors involved in the regulation of guanylate cyclase, 21 ' 22 and ANP has been shown to raise the intracellular cGMP level in cultured astroglia, 11 suggesting that ANP prevents the swelling of astroglia in brain tissue through regulation of sodium transport.…”

Section: Discussionmentioning

confidence: 99%

Effects of atrial natriuretic peptide on ischemic brain edema in rats evaluated by proton magnetic resonance method.

Shoji

Aoki

Takei

et al. 1991

Stroke

View full text Add to dashboard Cite

We examined the effect of atrial natriuretic peptide on cerebral edema in 96 rats. Forty-four rats were given 30 (TI=11), 120 (TI=26), or 150 (n=7) ftg/kg of the peptide intravenously over 24 hours after occlusion of the left middle cerebral artery to induce cerebral ischemia. We then measured the brain water content, the brain sodium and potassium contents, the in vitro proton nuclear magnetic resonance longitudinal (T,) and transverse (T 2 ) relaxation times, and the area of the edematous regions. Compared with saline treatment (n =39), peptide treatment decreased the brain water content in a dose-dependent manner and decreased the brain sodium content significantly (p<0.05). Peptide treatment also suppressed the lengthening of both T, and T 2 in edematous tissue (p<0.05 and p<0.01, respectively) and reduced the area of the edematous regions observed by magnetic resonance imaging (p<0.01). Atrial natriuretic peptide appears to have a pharmacological effect on ischemic brain edema, possibly by suppressing the elevation of water content through regulation of electrolyte transport in the brain. (Stroke 1991;22:61-65) S ince its initial discovery as a substance with a diuretic effect, 1 atrial natriuretic peptide (ANP) has been shown to be a unique hormone that regulates blood pressure and fluid homeostasis.2 -5 Recent studies have shown that this hormone regulates sodium transport in vascular endothelial 6 -7 and other 89 cells through activation of guanylate cyclase, suggesting that ANP may regulate water content in tissue.Binding sites for ANP have been found on brain microvessel endothelial cells 10 and astrocytes, 11 and elevated levels of guanosine 3',5'-cyclic monophosphate (cGMP) have been noted in these cells following ANP binding. In view of the known role of these cells in the origin and development of brain edema, 12-13 we inferred that ANP may have a pharmacological effect on brain edema. To investigate this hypothesis, we monitored changes in brain water, sodium, and potassium contents; changes in proton nuclear magnetic resonance (NMR) relaxation times From the Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.Supported in part by grants-in-aid for scientific research 01570817 and 02670636 from the Ministry of Education, Science, and Culture of Japan.Address for reprints: Shoji Naruse, MD, Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602, Japan.Received November 16, 1989; accepted August 29, 1990. in vitro; and changes in the area of edematous regions detected by in vivo magnetic resonance imaging (MRI) to examine the effects of ANP on ischemic brain edema induced in rats. Materials and MethodsWe used 96 male Wistar rats aged 8-11 weeks. Ninety-one rats were anesthetized with 50 mg/kg i.p. sodium pentobarbital. In eight sham-operated rats, the dura mater and arachnoid membrane were opened without middle cerebral artery (MCA) occlusion. In the other 83 rats, the main trunk of the left MCA was occluded...

show abstract

Radioautographic Localization of <sup>125</sup>I-Atrial Natriuretic Factor Binding Sites in the Brain

Cited by 55 publications

References 32 publications

Atrial Natriuretic Peptide Gene Delivery Reduces Stroke-Induced Mortality Rate in Dahl Salt-Sensitive Rats

Atrial Natriuretic Peptide Gene Delivery Reduces Stroke-Induced Mortality Rate in Dahl Salt-Sensitive Rats

Localization and Characterization of Binding Sites for Circulating and Cerebroventricular Atrial Natriuretic Factor in Rat Choroid Plexus

Effects of atrial natriuretic peptide on ischemic brain edema in rats evaluated by proton magnetic resonance method.

Contact Info

Product

Resources

About