31P saturation transfer and phosphocreatine imaging in the monkey brain.

Abstract

ABSTRACT31P magnetic resonance imaging with chemical-shift discrimination by selective excitation has been employed to determine the phosphocreatine (PCr) distribution in the brains of three juvenile macaque monkeys. PCr images were also obtained while saturating the resonance of the -phosphate of ATP, which allowed the investigation of the chemical exchange between PCr and the v-phosphate of ATP catalyzed by creatine kinase. Superposition of the PCr images over the proton image of the same monkey brain revealed topological variations in the distribution of PCr and creatine kinase activity. PCr images were also obtained with and without visual stimulation. In two out of four experiments, an apparently localized decrease in PCr concentration was noted in visual cortex upon visual stimulation. This result is interpreted in terms of a possible role for the local ADP concentration in stimulating the accompanying metabolic response. A D P 3 --P + H+ -ATP-+ H20Positron emission tomography (PET) studies on humans have shown that with visual stimulation blood flow and glucose consumption are increased (1-3). Localized proton MR studies have revealed a short-term increase in lactate concentration in the human brain upon visual stimulation (4). Thus it may be surmised from both PET and MR studies that glycolysis is important in visual stimulation. The local increase in cerebral oxygen consumption (mean = 5%, as measured by PET) due to somatosensory stimulation is less than the corresponding local increase in cerebral blood flow (mean = 29%) (5). Despite the small increase in the oxygen consumption noted in these PET studies, there appears to be a role for oxidative phosphorylation, although it seems from these studies that over longer times the role of the glycolysis reaction is significant. The role of the CK reaction is in provision and transport of ATP, but the question whether visual stimulation results in any increase in CK activity has not yet been addressed by these PET studies or by MR techniques.A further point is the interaction of these three pathways of putative energy synthesis. An intermediate common to all three pathways is ADP. The local concentration of free ADP may determine flux through oxidative phosphorylation (6); it may also influence flux through glycolysis at one or more sites but, particularly indirectly, through allosteric effects of ATP or AMP on phosphofructokinase (7). The concentration of ADP is in turn determined by equilibrium reactions, among which CK is most significant (8). We may, therefore, expect to obtain useful information about all three reactions by observation of PCr concentration and determination of the equilibrium of CK, from which ADP concentration can be calculated.The great heterogeneity of cerebral circulation and metabolism observed in PET studies leaves room for doubt about MR assays, which are only performed at a single time point and confined to the anticipated region of interest. To assess the response of the CK reaction to visual stimulation, it would be helpful to ...

Tissue- and cell-specific distribution of creatine kinase B: A new and highly specific monoclonal antibody for use in immunohistochemistry

“…The cell-type-specific expression of the B-isoform of creatine kinase (B-CK) has been studied in a wide vari ety of tissues from various species ranging from sea ur chin sperm (Tombes and Shapiro 1985), monkey brain (Mora et al 1991), rat kidney (Friedman and Perryman 1991) to human limb buds (Shinohara et al 1991). Thus far, however, the reports describing the distribution of B-CK within one species mostly concerned mRNA studies (Trask and Billadello 1990) or protein analysis of total tissue lysates (Dawson and Fine 1967;Yasmineh et al 1976;Argiroudis et al 1982;Beatty and Doxey 1983;Galitzer and Oehme 1985;Lindena et al 1986).…”

Myosin Va and myosin VI coordinate their steps while engaged in an in vitro tug of war during cargo transport

“…5F). Thus, myoVI can effectively anchor the cargo in the presence of micromolar ADP concentrations that are physiological (19,(35)(36)(37), which implies that the differential effects of ADP on myoV and myoVI (see Fig. 5 A and B) could serve as an in vivo regulator that links myoVI function to the metabolic state of the cell (19).…”

“…Here, we report that myoV is the dominant motor and that, as myoVI resists, it steps backward in coordination with myoV's forward steps. Although myoV dominating suggests that intracellular cargo transport would be unidirectional when equal numbers of both motors are present, myoVI can prevent myoV from dominating by myoVI shifting its role from transporter to anchor in the presence of ADP, thus, potentially linking cargo transport to the cell's metabolic state (19).…”

Non-Invasive Methods for Studying Brain Energy Metabolism: What They Show and What It Means

“…somatosensory or visual stimulation, cognitive tasks) with an increase in ATP turnover which is accessible to MRS. Some [18,[71][72][73][74], but not all [73,75], 31 P-MRS studies of visual activation have detected a fall in PCr. Magnetisation transfer studies detect an increase in creatine kinase exchange flux [74,75], probably reflecting a rise in ADP [22] (which could occur without PCr fall, as pH increases [72]).…”