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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: G-protein-coupled receptors (GPCRs) are the largest group of cell surface molecules involved in signal transduction and are receptors for a wide variety of stimuli ranging from light, calcium and odourants to biogenic amines and peptides. It is assumed that systematic genomic data-mining has identified the overwhelming majority of all remaining GPCRs in the genome. Here we report the cloning of a novel orphan GPCR which was identified in a search for erythropoietin-induced genes in the brain as a strongly up-regulated gene. This unknown gene coded for a protein which had a seven-transmembrane topology and key features typical of GPCRs of the A family but a low overall identity to all known GPCRs. The protein, coded ee3, has an unusually high evolutionary conservation and is expressed in neurons in diverse areas of the CNS with relation to integrative functions or motor tasks. A yeast two-hybrid screen for interacting proteins revealed binding to the microtubule-associated protein (MAP) 1b. Coupling to MAP1a has been described for another cognate GPCR, the 5-hydroxytryptamine (5HT) 2a receptor. Surprisingly, we found complete colocalization of ee3 and the 5HT2a receptor. The interaction with MAP1b proved to be critical for the stability or folding of ee3 as in mice lacking MAP1b the ee3 protein was undetectable by immunohistochemistry, although messenger RNA levels remained unchanged. We propose that ee3 is a highly interesting new orphan GPCR with potential connections to erythropoietin and 5HT2a receptor signalling.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2013
    Keywords: pH-Microclimate ; pH-Microelectrodes ; Colon ; Jejunum ; Guinea pig ; Rat ; in vitro ; in vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Segments of guinea pig jejunum, proximal and distal colon and of rat jejunum were superfused either in vivo or in vitro with different electrolyte solutions. The pH in the bulk phase solution and at the surface of the epithelium was measured with two different types of glass pH-microelectrodes, a pointed tip (Hinke-type) and a flat membrane electrode (Dubuisson-type); both types of electrodes gave the same results. The existence of a pH-microclimate at the surface of the mucosa was demonstrated under both in vivo and in vitro conditions. In vivo the pH-microclimate was stable and virtually independent of changes in the luminal bulk phase pH. When the bulk phase pH of the guinea pig colon was changed between pH 5 and pH 8.6, the mean pH in the microclimate was 7.08±0.15 (n=163) in the proximal colon and 6.91±0.14 (n=75) in the distal colon. In the guinea pig jejunum pH in the microclimate was 7.37±0.21 (n=10) while the luminal pH was 7.27±0.10. Under in vitro conditions, the pH in the microclimate was more acidic (guinea pig jejunum ΔpH 0.93, rat jejunum ΔpH 0.40, guinea pig proximal colon ΔpH 0.22). Addition of glucose (10 mM) or short-chain fatty acids (80–90 mM) to the luminal solution or replacement of sodium by lithium did not influence the pH in the microclimate significantly. Also the addition of acetazolamide, amiloride, SITS or sodium deoxycholate to the luminal solution, did not affect the pH in the microclimate in vivo. A temporary interruption of the blood supply caused acidification of the pH in the microclimate. Restoring the blood flow reversed the effect, and the pH returned to the original values within a few minutes. The originally proposed acid-microclimate could not be confirmed under in vivo experimental conditions either in the jejunum or in the colon by direct measurement with pH-sensitive glass-microelectrodes.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 362 (1976), S. 55-59 
    ISSN: 1432-2013
    Keywords: Pial arterial resistance ; Arterial resting tone ; Metabolic factors ; Cerebral blood flow ; Local regulation of pial arterial diameter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of adenosine upon pial resistance vessels was studied using local microapplication from the perivascular side and measurement of vascular diameter. Concentration-response curves revealed a concentration-dependent dilatatory effect of adenosine between 10−7 and 10−3 M. The degree of dilatation was independent of initial vessel size (47–260 μ). The dilatations due to adenosine could be reduced by theophylline in a reversible competitive antagonism. Concentration-response curves for theophylline yielded no vascular reaction at concentrations of up to 10−5 M theophylline. From these data it is concluded that the pial arterial resting tone is not influenced under our experimental conditions by adenosine formed and released by brain tissue. The dilatations measured at high theophylline concentrations are apparently due to a mechanism different from the adenosine antagonism.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 383 (1979), S. 29-34 
    ISSN: 1432-2013
    Keywords: Microcirculation ; Local control ; Brain ; Arterioles ; Tissue $$P_{O_2 } $$
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract $$P_{O_2 } $$ 's in the environment of the pial microvessels of the cat were measured using recessed tip oxygen microelectrodes. Measurements were made on the surface of vessels with internal diameters ranging from 200μm to 22μm. Blood oxygen partial pressures were also measured inside these vessels by penetrating the vessels with sharpened electrodes. Both intravascular and extravascular $$P_{O_2 } $$ values decreased progressively from the large arterial vessels down to the small arterioles. The observed values of intravascular $$P_{O_2 } $$ showed a systematic longitudinal decrease from 98.5±10.7 (SEM) mm Hg in the largest vessels down to 72.6±3.6 mm Hg in the smallest vessels. In addition to the longitudinal gradient, a transmural gradient was observed across the walls of the microvessels. The difference between blood $$P_{O_2 } $$ and vessel surface $$P_{O_2 } $$ was 27.0±2.5 mm Hg in the largest vessels and 6.0±2.2 in the smallest. The mean wall thickness in these groups of vesseis were 27.0±1.5 and 7.5±0.8 μm respectively. Measurements of the minimum tissue $$P_{O_2 } $$ on the exposed surface of the cortex yielded a value of 25.4±6.6 mm Hg. Systemic arterial partial pressure of oxygen averaged 94.7±4.7 mm Hg. The data indicate that significant gradients for oxygen exist both longitudinally and radially in association with the pial vessels. The longitudinal gradients represent losses of oxygen from the precapillary vessels. The transmural gradients are apparently the result of both consumption by the microvessel wall and diffusional gradients due to oxygen flux into the extravascular space.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Neurosurgical review 14 (1991), S. 163-168 
    ISSN: 1437-2320
    Keywords: Capillary density ; cerebrovascular resistance ; local cerebral blood flow ; local cerebral glucose utilization ; neuronal activity ; uncoupling of cerebral metabolism and blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Functional activity, metabolism and blood flow are locally heterogeneous in the brain, but tightly coupled. This adjustment occurs in two different ways: 1. Shortterm, dynamic coupling mediated by local vasoactive factors that ensure second-to-second regulation. 2. Long-term, static coupling apparently mediated by capillary density and developed in response to local functional and metabolic activity. Recognizing these two mechanisms permits one to distinguish apparent from real uncoupling. It allows the conclusion that there is no indication of an uncoupling of metabolism and blood flow during physiological conditions.
    Type of Medium: Electronic Resource
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