scholarly journals Bradykinin Receptors of Cerebral Microvessels Stimulate Phosphoinositide Turnover

1991 ◽  
Vol 11 (4) ◽  
pp. 557-566 ◽  
Author(s):  
Parvin Homayoun ◽  
Sami I. Harik
Keyword(s):  
Cerebral Cortex ◽  
Ligand Binding ◽  
Specific Binding ◽  
Receptor Site ◽  
Cerebral Microvessels ◽  
High Affinity ◽  
Phosphoinositide Turnover ◽  
Brain Microvessels ◽  
Brain Microcirculation ◽  
The Brain

We examined by ligand binding methods whether bradykinin (BK) receptors exist in rat and pig cerebral microvessels, and in the cerebral cortex from which the microvessels were isolated. We found a high-affinity and saturable BK receptor site in both rat and pig cerebral microvessels, but not in their cerebral cortex. The maximal density of binding and the dissociation constant were 8.0 ± 4.1 and 6.8 ± 1.5 fmol/mg of protein and 47 ± 24 and 150 ± 8 p M (mean ± SD) in cerebral microvessels of the pig and rat, respectively. The high-affinity specific binding of BK was effectively displaced by des-Arg0[Hyp3-Thi5–8,D-Phe7]BK, a specific B2 receptor antagonist, but not by des-Arg9[Leu8]BK, a specific B1 antagonist. We also demonstrated that BK increases phosphatidylinositol hydrolysis in cerebral microvessels of the rat and pig. This effect was also blocked by the B2, but not by the B1, antagonist. Increased phosphatidylinositol hydrolysis was manifested by a rapid transient increase in inositol trisphosphate and the later slow accumulation of inositol bisphosphate and inositol monophosphate. Preincubation of microvessels with phorbol ester, stable GTP analogs, pertussis toxin, or in Ca2+-free buffer did not influence BK activation of phosphatidylinositol hydrolysis. These results demonstrate the existence of BK receptors of the B2 subtype in brain microvessels, which may play an important role in modulation of the brain microcirculation, probably via increased phosphoinositide turnover.

scholarly journals Adenosine Receptors of Cerebral Microvessels and Choroid Plexus

1986 ◽  
Vol 6 (4) ◽  
pp. 463-470 ◽  
Author(s):  
Rajesh N. Kalaria ◽  
Sami I. Harik
Keyword(s):  
Cerebral Cortex ◽  
Ligand Binding ◽  
Choroid Plexus ◽  
Adenosine Receptors ◽  
Binding Sites ◽  
Specific Binding ◽  
Cerebral Microvessels ◽  
High Affinity ◽  
Receptor Sites ◽  
Ligand Binding Sites

We studied, by ligand binding methods, the two adenosine receptors, A, and A2, in rat and pig cerebral microvessels and pig choroid plexus. Ligand binding to cerebral microvessels was compared with that to membranes of the cerebral cortex. [3H]Cyclohexyladenosine and [3H]l-phenylisopropyladenosine were the ligands used for A1-receptors, and [3H]5'- N-ethylcarboxamide adenosine ([3H]NECA) was used to assess A2-receptors. We report that cerebral microvessels and choroid plexus exhibit specific [3H]NECA binding, but have no appreciable A1-receptor ligand binding sites. Specific binding of [3H]NECA to cerebral microvessels, choroid plexus, and cerebral cortex was saturable and suggested the existence of two classes of A2-receptor sites: high-affinity ( Kd ∼ 250 n M) and low-affinity ( Kd ∼ 1–2 μ M) sites. The Kd and Bmax of NECA binding to cerebral microvessels and cerebral cortex were similar within each species. Our results, indicating the existence of A2-receptors in cerebral microvessels, are consistent with results of increased adenylate cyclase activity by adenosine and some of its analogues in these microvessels.

scholarly journals Potential for imaging the high-affinity state of the 5-HT1B receptor: a comparison of three PET radioligands with differing intrinsic activity

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anton Lindberg ◽  
Ryosuke Arakawa ◽  
Tsuyoshi Nogami ◽  
Sangram Nag ◽  
Magnus Schou ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Specific Binding ◽  
Occipital Cortex ◽  
Intrinsic Activity ◽  
High Affinity ◽  
G Protein Coupled ◽  
Dose Dependent ◽  
The Brain ◽  
Agonist Affinity States ◽  
Different Doses

Abstract Background Over the last decade, a few radioligands have been developed for PET imaging of brain 5-HT1B receptors. The 5-HT1B receptor is a G-protein-coupled receptor (GPCR) that exists in two different agonist affinity states. An agonist ligand is expected to be more sensitive towards competition from another agonist, such as endogenous 5-HT, than an antagonist ligand. It is of interest to know whether the intrinsic activity of a PET radioligand for the 5-HT1B receptor impacts on its ability to detect changes in endogenous synaptic 5-HT density. Three high-affinity 11C-labeled 5-HT1B PET radioligands with differing intrinsic activity were applied to PET measurements in cynomolgus monkey to evaluate their sensitivity to be displaced within the brain by endogenous 5-HT. For these experiments, fenfluramine was pre-administered at two different doses (1.0 and 5.0 mg/kg, i.v.) to induce synaptic 5-HT release. Results A dose-dependent response to fenfluramine was detected for all three radioligands. At the highest dose of fenfluramine (5.0 mg/kg, i.v.), reductions in specific binding in the occipital cortex increased with radioligand agonist efficacy, reaching 61% for [11C]3. The most antagonistic radioligand showed the lowest reduction in specific binding. Conclusions Three 5-HT1B PET radioligands were identified with differing intrinsic activity that could be used in imaging high- and low-affinity states of 5-HT1B receptors using PET. From this limited study, radioligand sensitivity to endogenous 5-HT appears to depend on agonist efficacy. More extensive studies are required to substantiate this suggestion.

scholarly journals Adenosine Receptors and the Nucleoside Transporter in Human Brain Vasculature

1988 ◽  
Vol 8 (1) ◽  
pp. 32-39 ◽  
Author(s):  
Rajesh N. Kalaria ◽  
Sami I. Harik
Keyword(s):  
Cerebral Cortex ◽  
Human Brain ◽  
Choroid Plexus ◽  
Nucleoside Transporters ◽  
Receptor Subtypes ◽  
Nucleoside Transporter ◽  
Single Class ◽  
Cerebral Microvessels ◽  
High Affinity ◽  
Pial Vessels

Evidence suggests that adenosine modulates neuronal and cerebral vascular functions by interacting with specific receptors on brain cells and blood vessels. Adenosine and other nucleosides are also transported across the blood-brain barrier via a saturable, carrier-mediated mechanism. Using direct ligand binding methods, we studied the two adenosine receptor subtypes, A1 and A2, and the nucleoside transporter moiety in human brain microvessels, pial vessels, choroid plexus, and cerebral cortex membranes. The following specific tritiated ligands were used: cyclohexyladenosine (CHA) for A1 receptors; 5'- N-ethylcarboxamide adenosine (NECA) for A2 receptors; nitrobenzylthioinosine (NBMPR) and dipyridamole (DPY) for nucleoside transporters. We find that cerebral microvessels, pial vessels, and choroid plexus have few, if any, A1 receptors, in contradistinction to cerebral membranes, which have a 10–20-fold higher density of A1 receptor sites. Specific high-affinity NECA binding to A2 receptors in cerebral microvessels, pial vessels, and choroid plexus was saturable and was equivalent to that of cerebral cortical membranes. The Bmax and Kd of the high-affinity NECA binding to vessel preparations were ∼1.3 pmol/mg protein and ∼250 n M, respectively, which is similar to our previous findings in the rat and pig. NBMPR and binding were also saturable and were consistent with a single class of high-affinity binding sites. The density of nucleoside transporters was ∼four-fold higher in cerebral microvessels than in cerebral cortex, pial vessels, and choroid plexus. These results suggest that human cerebral microvessels have A2, but not A1, receptors and are particularly enriched with the adenosine transporter moiety.

Modulation by pineal gland of ouabain high-affinity binding sites in rat cerebral cortex

1992 ◽  
Vol 262 (4) ◽  
pp. R698-R706
Author(s):  
D. Acuna Castroviejo ◽  
J. L. Castillo ◽  
B. Fernandez ◽  
M. D. Gomar ◽  
C. M. del Aguila
Keyword(s):  
Cerebral Cortex ◽  
Pineal Gland ◽  
Binding Sites ◽  
Receptor Site ◽  
Rat Cerebral Cortex ◽  
Affinity Binding ◽  
Time Intervals ◽  
High Affinity Binding ◽  
High Affinity ◽  
Melatonin Administration

To investigate the participation of the pineal gland and its hormone melatonin on Na(+)-K(+)-ATPase (the sodium pump) in rat brain, we used Scatchard plots to analyze the changes in rat cerebral cortex of [3H]ouabain high-affinity binding in groups of intact, pinealectomized (PX), and sham-PX rats. Only one type of binding site, with a dissociation constant of approximately 3 nM and site number (Bmax) of approximately 250 fmol/mg protein, was apparent with our assay conditions. PX or sham-PX rats (subjected to surgery 15 days earlier) were killed at six different time intervals during the 24-h cycle. Intact and sham-PX animals showed a similar biphasic pattern in diurnal rhythm of ouabain binding, with a minimal concentration of binding sites at 1600 h and a maximal concentration at 0400 h. Pinealectomy induced a significant increase in Bmax at all time intervals studied, with the largest rise appearing at night and coinciding with the nocturnal peak, whereas the daytime minimum was blunted. Time-dependent experiments indicated that the Bmax of ouabain high-affinity binding in PX rats attained maximal values at 7 days after surgery and decreased somewhat 7 days later, while sham-PX animals showed only a small transient increase in Bmax up to 7 days after surgery, with values returning to normal by the 15th day. Melatonin administration at a single subcutaneous dose of 25 micrograms/kg body wt given 3 h before death was enough to counteract the PX-induced increase of ouabain high-affinity binding. Melatonin was able to enhance the binding of [3H]ouabain to its receptor site, increasing binding affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Absence of N-Methyl-D-Aspartate Receptors on Ovine Cerebral Microvessels

1988 ◽  
Vol 8 (6) ◽  
pp. 879-882 ◽  
Author(s):  
P. M. Beart ◽  
K-A. M. Sheehan ◽  
D. T. Manallack
Keyword(s):  
Gray Matter ◽  
Specific Binding ◽  
Acceptor Site ◽  
Sigma Receptors ◽  
Receptor Complex ◽  
Cerebral Microvessels ◽  
Brain Microvessels ◽  
Cerebral Microvasculature ◽  
Nmda Receptor Complex ◽  
Primary Acceptor

Radioreceptor methods were used to quantitate the N-methyl-D-aspartate (NMDA) receptor-complex of ovine cerebral microvessels and cerebral gray matter. Specific binding of D[3H]2-amino-5-phosphonopentanoate and [3H]1-[1-(2-thienyl)cyclohexyl]piperidine, ligands for the NMDA primary acceptor site and ionophore, respectively, was found in cerebral gray matter but was not detectable in membranes prepared from brain microvessels enriched in capillaries. Sigma receptors, another locus of action for phencyclidine congeners, were also not present on microvessels but were found in cortical homogenates. On the other hand, cerebral microvessels and gray matter contained significant numbers of β-adrenoceptors. Our results indicate the NMDA receptors and NMDA antagonists are unlikely to regulate the function of the cerebral microvasculature.

Relationship between levels and uptake of serotonin and high affinity [3H]imipramine recognition sites in the rat brain

1985 ◽  
Vol 63 (10) ◽  
pp. 1239-1244 ◽  
Author(s):  
Pavel D. Hrdina ◽  
Bruce A. Pappas ◽  
David C. S. Roberts ◽  
Robert J. Bialik ◽  
Cathrine L. Ryan
Keyword(s):  
Cerebral Cortex ◽  
Brain Regions ◽  
Serotonin Uptake ◽  
Noradrenaline Content ◽  
Serotonergic Neurons ◽  
High Affinity ◽  
Recognition Sites ◽  
Imipramine Binding ◽  
6 Hydroxydopamine ◽  
The Brain

High affinity [3H]imipramine binding, endogenous levels of serotonin and noradrenaline, and serotonin uptake were determined in brain regions of rats with selective destruction of serotonergic neurons by 5,7-dihydroxytryptamine (5,7-DHT), of adrenergic neurons by 6-hydroxydopamine (6-OHDA), and of rats treated with reserpine. Neonatal treatment with 5,7-DHT resulted in a significant decrease of both serotonin levels and density (Bmax) of high affinity [3H]imipramine binding sites in the hippocampus. In contrast, an elevation of serotonin levels and an increase in Bmax of [3H]imipramine binding were noted in the pons–medulla region. No changes were observed in the noradrenaline content in either of these regions. Intracerebral 6-OHDA lesion produced a drastic suppression of noradrenaline levels in cerebral cortex but failed to alter the binding affinity (KD) or density (Brnax) of [3H]imipramine recognition sites. A single injection of reserpine (2.5 mg/kg) resulted in marked depletion of both serotonin (by 57%) and noradrenaline (by 86%) content and serotonin uptake (by 87%) in the cerebral cortex but had no significant influence of the parameters of high affinity [3H]imipramine binding in this brain region. The results suggest that high affinity [3H]imipramine binding in the brain is directly related to the integrity of serotonergic neurons but not to the magnitude of the uptake or the endogenous levels of the transmitter, and is not affected by damage to noradrenergic neurons or by low levels of noradrenaline.

Uptake of Sodium Valproate and Effects on GABA Transport in Astroglial Primary Culture

1989 ◽  
Vol 16 (3) ◽  
pp. 244-247
Author(s):  
Michael Nilsson ◽  
Elisabeth Hansson ◽  
Lars Rönnbäck
Keyword(s):  
Valproic Acid ◽  
Cerebral Cortex ◽  
Sodium Valproate ◽  
Gaba Uptake ◽  
Newborn Rat ◽  
Gaba Transport ◽  
High Affinity ◽  
Major Factors ◽  
The Brain ◽  
Anticonvulsant Effects

The sodium salt of valproic acid (VPA) is an antiepileptic drug, which is effective in the treatment of several types of epilepsy. The drug has been postulated to exert its anticonvulsant effects by interaction with GABA-ergic systems in the brain. Results show a high-affinity uptake for sodium valproate in primary astroglial cultures from newborn rat cerebral cortex, with the kinetic parameters Km and Vmax not significantly different from those observed for GABA. This uptake was shown to interact with astroglial GABA transport in culture, with an increased Km value for GABA uptake. Since failure in GABA-ergic systems is postulated to be one of the major factors in the aetiology of epilepsy, it is interesting to note that the transport system for GABA in astrocytes is affected by sodium valproate.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

Neurotransmitter systems of female mouse brain during growth of malignant melanoma modeled on the background of chronic pain

2018 ◽  
pp. 49-55
Author(s):  
О.И. Кит ◽  
И.М. Котиева ◽  
Е.М. Франциянц ◽  
И.В. Каплиева ◽  
Л.К. Трепитаки ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Cerebral Cortex ◽  
Malignant Melanoma ◽  
Sciatic Nerve ◽  
Female Mouse ◽  
Combined Effects ◽  
Malignant Growth ◽  
Course Of Disease ◽  
The Brain ◽  
Melanoma Growth

Известно, что биогенные амины (БА) участвуют в злокачественном росте, их уровень изменяется в ЦНС при болевом воздействии, однако исследований о сочетанном влиянии хронической боли (ХБ) и онкопатологии на динамику БА в головном мозге не проводилось. Цель: изучить особенности баланса БА в коре головного мозга в динамике роста меланомы, воспроизведенной на фоне ХБ. Материалы и методы. Работа выполнена на 64 мышах-самках, весом 21-22 г. Животным основной группы меланому В16/F10 перевивали под кожу спины через 2 недели после перевязки седалищных нервов. Группой сравнения служили мыши с меланомой без боли. Уровни БА: адреналина, норадреналина, дофамина (ДА), серотонина (5-НТ), гистамина, а также 5-ОИУК определяли методом иммуноферментного анализа. Результаты. У мышей с ХБ уменьшается содержание большинства БА, однако уровень ДА не изменяется. Метаболизм 5-НТ происходит с участием МАО. Развитие меланомы сопровождается увеличением содержания ДА и 5-НТ, тогда как МАО - ингибируется. Направленность сдвигов БА при развитии меланомы на фоне ХБ оказалась практически такой же, как и без неё. В то же время ХБ ограничивает накопление 5-НТ в коре мозга при меланоме, что сопровождается более агрессивным её течением. Выводы. ХБ ограничивает включение стресс-лимитирующих механизмов в головном мозге при развитии меланомы у мышей, что приводит к более агрессивному течению злокачественного процесса. Biogenic amines (BA) are known to be involved in malignant growth, and their CNS levels change in pain; however, there are no studies of combined effects of chronic pain (CP) and cancer on BA dynamics in the brain. Aim: To study features of BA balance in the cerebral cortex during melanoma growth associated with CP. Material and methods. The study included 64 female mice weighing 21-22 g. In the main groups, B16/F10 melanoma was transplanted under the skin of the back two weeks following sciatic nerve ligation. Mice with melanoma without pain were used as the control. Concentrations of BA: adrenaline, noradrenaline, dopamine (DA), serotonin (5-HT), histamine and 5-HIAA were measured with ELISA. Results. Concentrations of BAs decreased in mice with CP although DA levels did not change. 5-HT metabolism involved MAO. The development of melanoma was accompanied by increases in DA and 5-HT whereas MAO was inhibited. The direction of BA changes during the development of melanoma was the same with and without CP. At the same time, CP with melanoma limited accumulation of 5-HT in the cerebral cortex, which resulted in even more aggressive course of cancer. Conclusion. CP restricted the activation of cerebral stress-limiting mechanisms during the development of melanoma in mice, which resulted in a more aggressive course of disease.

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