Stimulatory Effect of the D2 Antagonist Sulpiride on Glucose Utilization in Dopaminergic Regions of Rat Brain

Local cerebral glucose utilization (LCGU) was measured, using the quantitative autoradiographic [14C]2-deoxy-D-glucose method, in 56 brain regions of 3-month-old, awake Fischer-344 rats, after intraperitoneal administration of sulpiride (SULP) 100 mg/kg. SULP, an "atypical" neuroleptic, is a selective antagonist of D2 dopamine receptors. LCGU was reduced in a few nondopaminergic regions at 1 h after drug administration. Thereafter, SULP progressively elevated LCGU in many other regions. At 3 h, LCGU was elevated in 23% of the regions examined, most of which are related to the CNS dopaminergic system (caudate-putamen, nucleus accumbens, olfactory tubercle, lateral habenula, median eminence, paraventricular hypothalamic nucleus). Increases of LCGU were observed also in the suprachiasmatic nucleus, lateral geniculate, and inferior olive. These effects of SULP on LCGU differ from the effects of the "typical" neuroleptic haloperidol, which produces widespread decreases in LCGU in the rat brain. Selective actions on different subpopulations of dopamine receptors may explain the different effects of the two neuroleptics on brain metabolism, which correspond to their different clinical and behavioral actions.     

Effect of Digestion with Phospholipase A2 on Endogenous Protein Phosphorylation in Particulate Fractions from Rat Brain Synaptosomes

The endogenous phosphorylation of synapsin 1 in cyclic AMP-containing media was greatly decreased by digestion of synaptic vesicles and synaptosomal membranes with phospholipase A2, suggesting that the system is functionally dependent on the membrane structure. Treatment of the synaptic vesicle fraction with phospholipase A2 also caused a small but significant inhibition of the Ca2+/calmodulin-dependent phosphorylation of the same protein. The Ca2+/calmodulin-dependent phosphorylation of other major acceptors, and the basal phosphorylation of a 52-kD acceptor enriched in the vesicle fraction, remained unchanged after cleavage of the membrane phospholipids with phospholipase A2. The significance of the selective effect of phospholipase A2 treatment on endogenous membrane phosphorylation is discussed.     

2-Amino-7-Phosphonoheptanoic Acid Inhibits Insulin-Induced Convulsions and Striatal Aspartate Accumulation in Rats with Frontal Cortical Ablation

Pretreatment of rats with the excitatory amino acid antagonist 2-amino-7-phosphonoheptanoic acid (2-APH; 0.5 mmol/kg, i.p.) protected against insulin-induced clonic seizures. Complete protection was observed in 38% of the rats and partial protection in an additional 50%. Lesioning of the corticostriatal pathway by frontal cortical ablation caused decreases in the striatal levels of aspartate (-28%) and glutamate (-18%), an increase in striatal glutamine level (45%), and decreased high-affinity uptake of D-[3H]aspartate (-27%) in the lesioned dorsal neostriatum. Insulin-induced hypoglycemia caused a predicted sharp increase in aspartate level (165%) and decreased glutamate (-20%) and glutamine (-38%) levels in the intact striatum. Pretreatment of rats with 2-APH significantly reversed the insulin-induced changes in striatal aspartate, glutamate, and glutamine levels, especially in the intact hemisphere. In normoglycemic control rats, the "metabolic," i.e., concentration in the lesioned hemisphere, aspartate pool constituted 72% and the "synaptic," i.e., the concentration difference between the intact and lesioned hemispheres, 28% of the total striatal aspartate pool. 2-APH had no effect on the level of "metabolic" aspartate in the striata of normoglycemic rats but caused an almost complete suppression of "synaptic" aspartate. Following insulin-induced hypoglycemia, the "metabolic" aspartate pool doubled, whereas the "synaptic" aspartate pool increased 3.5-fold in the absence of 2-APH. The insulin-induced rise in "synaptic" aspartate level was almost completely blocked by 2-APH (a 5% rise instead of a 3.5-fold rise).(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental evidence on the affinities ofPapaver somniferum (Papaveraceae)

Results obtained from crossing experiments betweenP. somniferum subsp.somniferum (2n = 22) and subsp.setigerum (2n = 44),P. glaucum (2n = 14) andP. gracile (2n = 14) and from the observation of meiotic chromosome pairing in the various hybrids obtained do not provide straightforward evidence for the hypothesis thatP. somniferum originated as a triploid hybrid between taxa similar toP. glaucum andP. gracile (Kadereit 1986a, b).—On the one hand, the pattern of crossability found reflects the closer similarity of subsp.somniferum toP. glaucum and of subsp.setigerum toP. gracile, which was interpreted as segregation of parental characters, and the high frequency of 2n = 28 chromosomes among F₂-progeny from the hybrid subsp.somniferum × subsp.setigerum (2n = 33) might reveal n = 7 as the base number also ofP. somniferum. On the other hand, however, the general difficulty of obtaining hybrids, and the low incidence of bivalent formation in their meiosis, probably indicating a lack of chromosome homology between the different species, do not fit the above hypothesis.—These results are in marked contrast to the morphological similarity between the three species involved.     

Identity of common phosphoprotein substrates stimulated by interleukin 2 and diacylglycerol suggests a role of protein kinase C for IL 2 signal transduction

Interleukin 2 (IL 2) is a polypeptide growth factor essential for the proliferation and differentiation of T lymphocytes, large granulocytic lymphocytes, and, potentially, cells of the antibody-producing lineage, B lymphocytes. Many of the biological properties of IL 2 may be mimicked or potentiated by a potent class of tumor promoters, phorbol esters. Phorbol esters have recently been shown to associate with and activate a unique phospholipid/Ca2+-dependent phosphotransferase, protein kinase C (PK-C). Utilizing two-dimensional gel electrophoresis, we have compared the IL 2 and diacylglycerol-induced protein phosphorylation patterns of several IL 2-dependent murine cell lines. Both IL 2 and synthetic diacylglycerol, 1-oleyl-2-acetylglycerol (OAG), stimulated phosphorylation of a number of protein substrates in intact cells compared to unstimulated controls. Three groups of substrates were identified; the first showed increased phosphorylation following stimulation with either IL 2 or OAG, while the second and third groups showed increased phosphorylation following stimulation with IL 2 but not OAG, and with OAG but not IL 2, respectively. Here, we characterize the kinetics of phosphorylation of one cellular substrate, p68, which appears to be phosphorylated in response to direct activators of PK-C or lymphoid or myeloid growth factors in their respective lineage cell lines. The observation that IL 2 also stimulates a unique series of phosphoproteins in addition to those induced by direct PK-C activators suggests that IL 2 may initiate additional protein kinase activities, unrelated to PK-C, which may also be critical for the ligand-receptor signal transduction process regulating growth and gene expression.     

Types I and IV collagenolytic and plasminogen activator activities in preovulatory ovarian follicles

During ovulation, enzymatic degradation of the extracellular matrix occurs within and around the graafian follicles. In this study, the activities of several different proteolytic enzymes were measured in the culture media of follicles taken from pregnant mare serum gonadotropin (PMSG)-primed immature rats. At 52 h after PMSG, the follicles were cultured for 2 to 15 h in media with or without human chorionic gonadotropin (hCG). Type I collagenase activity in hCG-stimulated follicles gradually increased within 6 h to 3.3-fold above that of the controls. Relatively pure populations of granulosa cells produced type I collagenase to a similar extent. Likewise, type IV collagenase increased 3.8-fold by 6 h after exposure of the follicles to hCG. In contrast, plasminogen activator activity increased by 3.9-fold at 2 h after hCG, but was negligible at 4, 6, and 15 h after incubation. These results suggest that plasminogen activator may activate both type I and type IV collagenase in hCG-stimulated ovulatory follicles.     

An investigation into thee mechanism of citrate---FE-dependent lipid peroxidation

Chelation by citrate was found to promote the autoxidation of Fe²⁺, measured as the disapperance of 1,10-phenanthroline-chelatable Fe²⁺. The autoxidation of citrate---²⁺ could in turn promote the peroxidation of microsomal phospholipid liposomes, as judged by malondialdehyde formation. At low citrate---Fe²⁺ ratios the autoxidation of Fe²⁺ was slow and the formation of malondialdehyde was preceded by a lag phase. The lag phase evidence of this, linear initial rates of lipid peroxidation were obtained via the combination of citrate---Fe²⁺ and citrate---Fe³⁺, optimum activity occurring at a Fe³⁺---Fe²⁺ ratio of 1:1. Evidence is also presented to suggest that the superoxide and the hydrogen peroxide that are formed during the autoxidation of citrate---Fe²⁺ can either stimulate or inhibit lipid peroxidation by affecting the yield of citrate---Fe³⁺ from citrate---Fe²⁺. No evidence was obtained for the participation of the hydroxyl radical in the initiation of lipid peroxidation by citrate---Fe²⁺.     

Docosahexaenoate-containing phospholipids in sarcoplasmic reticulum and retinal photoreceptors. A proposal for a role in Ca2+-ATPase calcium transport

A critical review of the experimental literature concerning the metabolism of all-cis-4, 7, 10, 13, 16, 19-docosahexaenoate-containing phospholipids in muscle and retina suggests that it plays an essential role in maximizing the Ca²⁺/ATP stoichiometry of the Ca²⁺-ATPase of sarcoplasmic reticulum and retinal photoreceptor disks. Docosahexaenoate-phosphatidylcholine is proposed to participate in oligomerization of Ca²⁺-ATPase necessary for the establishment of a high Ca²⁺/ATP coupling ratio of the Ca²⁺ pump in these tissues. Possible tests of this hypothesis are presented.     

Fucosyltransferase expression in human platelets and leucocytes

The activities of -2-l-fucosyltransferase and -3-l-fucosyltransferase were measured in human platelets and leucocytes from normal donors, -2-l-Fucosyltransferase was found in platelets but not in leucocytes. In contrast -3-l-fucosyltransferase was not detected in platelets but was present in leucocytes where it was demonstrated in the neutrophil, monocyte and lymphocyte fractions.     

Simultaneous butyrate oxidation by Syntrophomonas wolfei and catalytic olefin reduction in absence of interspecies hydrogen transfer

Methanogenesis by a Syntrophomonas wolfei/ Methanospirillum hungatei coculture was inhibited in presence of ethylene and the hydrogenation catalyst Pd-BaSO₄. However, butyrate oxidation by S. wolfei continued and ethylene was reduced to ethane. Per mol of butyrate oxidized, 2.4 mol acetate was produced and 0.8 mol ethylene was reduced. Acetylene, propylene and butene were less effective as H₂ acceptors than ethylene, and addition of bromoethanesulfonic acid was necessary to inhibit methanogenesis in the presence of the two longer-chain olefins. Other hydrogenation catalysts were less effective in the order Pd-charcoal < PE-asbestos < Pd-PEI beads < Pt-Al₂O₃, Pd-CaCO₃. Optimal ethylene hydrogenation was achieved with still incubation in presence of 7.2 mg Pd-BaSO₄ and 0.7 g sand per ml medium. The higher catabolic rate of S. wolfei in presence of the methanogen indicated that the biological H₂ removal mechanism was more efficient than the catalytic olefin reduction.Abbreviations BES bromoethane sulfonic acid - VFA volatile fatty acid