Angiotensin II binding sites were localized and quantified in individual brain nuclei from single rats by incubation of tissue sections with 1 nM 125I-[Sar1]-angiotensin II, [3H]-Ultrofilm autoradiography, computerized microdensitometry and comparison with 125I-standards. High angiotensin II binding was present in the circumventricular organs (organon vasculosum laminae terminalis, organon subfornicalis and area postrema), in selected hypothalamic nuclei (nuclei suprachiasmatis, periventricularis and paraventricularis) and in the nucleus tractus olfactorii lateralis, the nucleus preopticus medianus, the dorsal motor nucleus of the vagus and the nucleus tractus solitarii. High affinity (KA from 0.3 to 1.5 X 10(9) M-1) angiotensin II binding sites were demonstrated in the organon subfornicalis, the nucleus tractus solitarii and the area postrema after incubation of consecutive sections from single rat brains with 125I-[Sar1]-angiotensin II in concentrations from 100 pM to 5 nM. These results demonstrate and characterize brain binding sites for angiotensin II of variable high affinity binding both inside and outside the blood-brain barrier.

Angiotensin II↗

PubMedDate not supplied

Synthesis and theoretical study of 2-amino-2,3,3a,4,5,6-hexahydro-1H-phenalene and its biological evaluation on central dopaminergic system.

Compound 2 considered as a rigid non-hydroxylated 2-amino tetralin was synthesized and biologically evaluated. Central administration of compound 2 (50 microg or 100 microg/10 microl) induced a reduction in urinary sodium and potassium excretion at 3 and 6 h of urine collection. We speculate that compound 2 may be acting as a dopamine receptor antagonist.

Amines↗

PubMedDate not supplied

Binding of angiotensin and atrial natriuretic peptide in brain of hypertensive rats.

Atrial natriuretic peptides, produced in the mammalian cardiac atrium, are released into the general circulation and may be actively involved in the control of blood pressure and in fluid homeostasis as antagonists of the peripheral angiotensin system. Certain cardiovascular effects of atrial natriuretic peptides may be centrally mediated, as binding sites for atrial natriuretic factor (8-33) (ANF) have been localized to the subfornical organ. This circumventricular structure lacks a blood-brain barrier and is therefore accessible to circulating peptides. It contains large numbers of angiotensin II (AII) binding sites, and has been suggested as the main central site of action for circulating AII in the regulation of blood pressure and fluid metabolism. Here we have studied binding sites for rat atrial natriuretic peptide(6-33) (rANP) and AII in the brains of spontaneously (genetic) hypertensive rats (SHR) and their normotensive controls, Wistar Kyoto (WKY) rats, by quantitative autoradiography. Binding sites for both peptides were highly localized in the subfornical organ. The number of rANP binding sites was decreased in the subfornical organ of both young (4 weeks old) and adult (14 weeks old) SHR compared with age-matched normotensive controls. Conversely, the number of AII binding sites was higher in both young and adult SHR compared with WKY rats. Our results suggest a central role for rANP and AII in genetic hypertension; they may act as mutual antagonists in brain areas involved in control of blood pressure and fluid regulation.

Age Factors↗

PubMedDate not supplied

Interferon response sequence potentiates activity of an enhancer in the promoter region of a mouse H-2 gene.

The expression of class I transplantation antigens encoded in the major histocompatibility complex (H-2 in mouse, HLA in man) can be induced by alpha-, beta- and gamma-interferons. Both transcriptional and post-transcriptional mechanisms have been postulated. Recently, a common sequence has been found in the promoter region of several human genes responsive to IFN-alpha. The promoters of H-2Kb and several other mouse class I genes contain a similar interferon response sequence. We show here, in a transient assay, that the H-2Kb promoter can be induced by all three types of interferon and that the interferon response sequence is necessary for induction to occur. However, the response sequence is active only when associated with a functional enhancer sequence which we have recently identified in the promoter of H-2Kb and other class I genes. The combination of these two sequences can render a heterologous promoter responsive to interferon, irrespective of its orientation relative to the cap site.

Animals↗

PubMedDate not supplied

P53-independent apoptosis: a mechanism of radiation-induced cell death of glioblastoma cells.

PURPOSE: Radiation therapy, though routinely used in the treatment of patients with glioblastoma multiforme, is of limited efficacy in extending patients' lives. In this study we investigated the mechanism by which ionizing radiation causes death of glioblastoma cells in the hope of ultimately altering the intrinsic radioresistance of glioblastoma tumors. METHODS: Radiation survival in vitro was quantitated using linear quadratic and repair-saturation mathematical models. Radiation-induced apoptosis was assayed by fluorescence-activated cell sorter analysis, terminal deoxynucleotide transferase labeling technique, and chromatin morphology. Cellular distribution within the cell cycle was quantitated by dual labeling with propidium iodide and bromodeoxyuridine. RESULTS: We examined whether in vitro clonogenic radioresistance of glioblastoma would reflect their susceptibility to radiation-induced apoptosis and their ability to undergo a G1 arrest--two cellular functions associated with wild-type p53 expression. We demonstrated that apoptosis contributed to the cytocidal effect of ionizing radiation on glioblastoma cells. The apoptosis observed in glioblastoma cell lines occurred in the absence of wild-type p53 expression. We identified a glioblastoma cell line expressing wild-type p53 and found that it did not exhibit radiation-induced apoptosis but rather underwent a prolonged G1 arrest not observed in any glioblastoma cell line lacking wild-type p53 expression. CONCLUSION: Apoptosis is an important component of the lethal effect of ionizing radiation on glioblastoma cells and does not require wild-type p53 expression. Glioblastoma expressing wild-type p53 exhibited no apoptosis, even after high radiation doses, but rather underwent a prolonged G1 arrest. The observation of p53-independent apoptosis and p53-dependent Gi arrest in glioblastoma cells have important radiobiologic and clinical implications.

Apoptosis↗