Effects of selective cholecystokinin antagonists L364,718 and L365,260 on food intake in rats

The selective type A and B cholecystokinin (CCK) receptor antagonists L364,718 and L365,260 were used to identify the receptor subtype that mediates the satiety effect of endogenous CCK. Male rats (n = 12–13/group), fed ground rat chow ad lib, received L364,718 (0, 1, 10, 100, or 1000 μg/kg IP) or L365,260 (0, 0.1, 1, 10, 100, 1000, or 10,000 μg/kg IP) 2 h after lights off, and food intake was measured 1.5, 3.5, and 5.5 h later. L364,718 significantly stimulated 1.5-h food intake by more than 40% at 10 μg/kg and higher doses; cumulative intake at 3.5 and 5.5 h remained elevated by about 20% at 1000 and 100 μg/kg of L364,718, respectively. In contrast, L365,260 had no significant stimulatory effect on feeding at any dose. The potency of L365,260 for antagonizing gastrin-stimulated gastric acid secretion was examined in unanesthetized rats. Male rats (n = 14), prepared with gastric and jugular vein cannulas, received doubling doses of gastrin (G-17I) (0.16–5 nmol/kg/h IV), each dose for 30 min, and gastric juice was collected for each 30-min period. G-17I stimulated gastric acid output dose dependently; the minimal effective dose was 0.16 nmol/kg/h, while maximal output (5-fold above basal) occurred at 5 nmol/kg/h. L365,260 (0, 1, 10, 100, 1000, or 10,000 μg/kg IV), administered 30 min before continuous infusion of G-17I (1.25 or 5 nmol/kg/h), significantly inhibited acid output only at 10,000 μg/kg; cumulative 60-min output was decreased by 60%. These results suggest that CCK acts at CCK-A receptors to produce satiety during the dark period in ad lib-feeding rats.     

Inactivation of bradykinin and kallidin by cathepsin G and mast cell chymase

Human neutrophil cathepsin G and human skin chymase can inactivate bradykinin by cleavage at the carboxy terminal phenylalanyl-arginyl peptide bond of this polypeptide. The mast cell enzyme is far more effective than cathepsin G, the rates of hydrolysis being comparable to that found for angiotensin I to angiotensin II conversion (C.F. Reilly, D. Tewksbury, N. Schechter, and J. Travis, J. Biological Chemistry 257:8619-8622). This ability to both inactivate bradykinin and accelerate the production of angiotensin II may be of significance in the development of biochemical events associated with inflammation.     

Partitioning of pulmonary resistance during constriction in the dog: effects of volume history

We assessed the relative changes in airways and lung tissue with bronchoconstriction, and the changes in each during and following a deep inhalation (DI). We partitioned pulmonary resistance (RL) into airway (Raw) and tissue (Vtis) components using alveolar capsules in 10 anesthetized, paralyzed, and open-chested dogs ventilated sinusoidally with 350-ml breaths at 1 Hz. We made measurements before and during bronchoconstriction induced by vagal stimulation or inhalation of histamine or prostaglandin F2 alpha (PGF2 alpha), each of which decreased dynamic compliance by approximately 40%. With histamine and PGF2 alpha the rise in RL was predominantly due to Vtis. With vagal stimulation there was a relatively greater increase in Raw than Vtis. At higher lung volumes, Vtis increases offset falls in Raw, producing higher RL at these volumes before and during constriction with PGF2 alpha and histamine. During constriction with vagal stimulation, the fall in Raw with inflation overrode the rise in Vtis, resulting in a lower RL at the higher compared with the lower lung volume. The changes seen after a DI in the control and constricted states were due to alterations in tissue properties, both viscous and elastic. However, the relative hysteresis of the airways and parenchyma were equal, since Raw, our index of airway size, was unchanged after a DI.     

Absorption and imagery locate immune responses in the body

Imagery instructions specifying mucosal immunity should alter mucosal immunoglobulin A (m-IgA) levels in high absorbers, whose intent concentration evokes intense physiological responses. After screening for health status, 121 high or low absorbers were randomly assigned to either Relaxation Alone (R), Relaxation with Mucosal Immune Imagery (RI), or Vigilance Task control (VT). Before and after one 60-min intervention, subjects reported theory-relevant psychological variables and provided 5ml whole saliva, which was immediately frozen and assayed lateren masse with enzyme-linked immunoabsorbence (ELISA). MANOVA analysis of psychological variables replicated past research. ANOVA on residualized m-IgA found Time × Absorption interaction and Condition main effects. High more than low absorbers responded to relaxation with mucosal immune imagery by producing higher m-IgA. High absorbers appear able to locate where their immune systems will respond. Individual differences like absorption level need to be emphasized in diagnosis and treatment responsiveness.National Institutes of HealthM. Banks (Jasnoski) Gregerson, Department of Psychology, The George Washington University, changed to The Family Therapy Institute; Ingram M. Roberts, The George Washington University Medical Center, changed to Department of Medicine, Bridgeport Hospital; and Michael M. Amiri, The George Washington University Medical Center, changed to the Department of Neuroscience, NINDS Branch, National Institutes of Health. This research supported by an intra-mural BioMedical Research Grant from The George Washington University, was presented at the 1992 Annual Meeting of the Eastern Psychological Association, Boston, Massachusetts. Special thanks are extended to the following students who assisted instrumentally at various stages: undergraduates Lina Alathari, S. Theodor King, Beth Lieberman, Parisa Lotfi, Anita McClenon, and Karen Siscoe, and graduate student Mariken Hasert.     

Nucleosome-associated protein kinases in murine erythroleukemia cells.

Chromatin subunits from murine erythroleukemia cells were prepared by a method which releases actively transcribing genes. Two casein kinase activities (CK₁ and CK₂) were isolated from these nucleosomes by gel nitration in 0.5 m NaCl. CK₁ (M_r ~ 200,000) and CK₂ (M_r ~ 35,000) were further purified by phosphocellulose chromatography and characterized with regard to several parameters which may regulate their activity in vivo. CK₁ has an NaCl optimum of 0.14 m, utilizes GTP as phosphate donor ~25% as efficiently as ATP, and phosphorylates a discrete group of high molecular weight nonhistone proteins in the unfractionated chromatin starting material. CK₂ has an NaCl optimum of 0.24 m, cannot utilize GTP, and modifies a different group of nonhistones. Both kinases are inhibited by concentrations of hemin (<50 μm) which efficiently induce globin gene expression in erythroleukemia cells. A histone kinase resolved during the gel filtration step is unaffected by hemin. An investigation of the mode of hemin inhibition reveals that CK₁ and CK₂ interact in different fashions with the inhibitor.     

Reversion of Texas male-sterile cytoplasm maize in culture to give fertile,T-toxin resistant plants

Summary Plants carrying Texas male-sterile (Tms) cytoplasm are normally sensitive to Drechslera maydis T-toxin. Tissue cultures were initiated from immature embryos of maize carrying Tms-cytoplasm, and plants were regenerated after selection for resistance to T-toxin. Fertile, T-toxin resistant plants were obtained from the unselected control cultures as well as from the selected material. In addition, one regenerant from an unselected culture was fertile and T-toxin sensitive. The progeny of the regenerants showed the phenotype of the female parent with respect to pollen-fertility, and T-toxin resistance. The data are consistent with the heritable changes observed being the result of the expression of an altered mitochondrial genome.     

The immune response of brown trout (Salmo trutta L.) to injection with soluble antigens.

The immune response of brown trout (Salmo trutta) to horse serum and keyhole limpet haemocyanin was studied. Intraperitoneal and intramuscular injections were used, with and without adjuvant, in 209 fish. Complement-fixing antibodies (CFA) and precipitins were produced to both antigens. CFA were detected after 8 days to haemocyanin and after 13 days to horse serum. Maximum CFA titres to a single intraperitoneal injection of horse serum or haemocyanin were reached at 44 and 43-46 days respectively. Precipitins to a single injection of haemocyanin given intraperitoneally were detected after 19 days using gel diffusion. Similarly using the intramuscular route they were detected after 22 days. However, using counter-current electrophoresis, precipitins were detected after 8 days by the intraperitoneal route and after 9 days by the intramuscular. Precipitins to horse serum given intraperitoneally were demonstrated after 22 days by both gel diffusion and counter-current electrophoresis. Fish given 2 intraperitoneal injections of haemocyanin in adjuvant reached maximum CFA titres after 55 days; a 3rd injection on day 56 did not produce a marked increase in titre. Fish given intramuscular injections of haemocyanin in adjuvant showed maximum CFA titres at day 43. After a 3rd injection on day 56, maximum CFA titres were reached between days 92 and 106. Intramuscular injections gave significantly higher titres than those given by the intraperitoneal route. Some fish which showed no precipitins by gel diffusion were positive by counter-current electrophoresis. Precipitating antibodies to haemocyanin migrating in the beta2-gamma1 region were detected by immuno-electrophoresis.