204 resultados para shake
Resumo:
Top Row: Lynn L. Applin, Amy Benner, Paula Broderick, Lisa B. Cohan, Catherine Collard, Beth A. Crawford, Cathleen M. Cupal, Andrea De Agoslino, Marivi G. Del Rosario, Patricia A. Dork, Nancy Farrington, Susan Foltz, Holly Franckowiak, Mary Franklin
Row 2: Kelly Garlow, Kathleen Gold, Renee Harris, Jody Becsey, Susan Bowman, Ann Marie Francel, Shelia Remy Smith, Sharon L. Holewinski, Colleen Kennedy, Dee Dee Hebert, Carolyn A. Hejkal, Wendy L. Hepworth
Row 3: Vicloria A. Hershey, Laura A. Hines, Jean Horner, Kimberly J. Howe, Joan L. Ilseman, Mary Jo Jay
Row 4: Suzanne Jennings, Suzanne Johnson, Janet Kaplan, Ann V. Kealy, Mary King, Lisa M. Kluk, Jane G. Kromer, Michelle Lajiness, Donna LaRoy, Christine Y. Lee
Row 5: Heidi Lewis, Betsy Livingston, Leslie Loll, Karen B. Majeske, Rita A. Markel, Megan McDonald, Sara J. McKenna, Jacquelin Merva, Monique A. Michael, Barbara Mueller
Row 6: Sandra Nelson, Barbara Nemenzik, Sherry Novak, Kristin Olson, Roberta A. Paas-Duda, Janet Patterson, Michelle L. Pecot, Dawn M. Popovics, Elizabeth Powaser, Cynthia J. Rabette
Row 7: Julie Ray, Susan M. Rice, Anne L. Richardson, Nancy Rockwell, Rhetaug G. Dumas, Cheryl E. Easley, Shake Ketefian, Janice B. Lindberg, Ruth E. Rogers, Nancy Schultz, Jean Schuster, Jean Scicluna
Row 8: Kathleen A. Sobczak, Mary Sokolik, Cheryl Stoyka, Vickie T. Sullivan, Susan A. Thompson, Margaret Venglarik, Sharon L. Wagner, Dorathy J. Washington, John J. Williams, Linda S. Wineland, Yvette L. Winia, Jody Wiser, Shannon H. Wright
Resumo:
Top Row: Douglas G. Pointon, Anne M. Laliberte, Anne T. Reaume, Karen R. Anderson, Margaret A. Mehall, Laura Meintel(Cepko), Sharon M. Milberger, Felicia I. Kle??, Pamela J. DcKeyser, Kathryn G. Maudlin, Mary C. Downey, Julie A. Gergen, Anne K. Hubling, Helen Mourao, Deborah L. Dubrul, Sarah E. Whorf
Row 2: Andrea Mitchell, Karen E. Grost, Paula V. Nersesian, Kelly A. Fleming, Mary Beth Morton, Lynda L. Cooley, Cynthia A. Wandzel, Deborah L. Bach, Karen A. Schwartz, Rhonda G. Pasma, Lesley M. Shafer, Michelle A. Kauer, Mary Jo Raftery, Carol A. Hammell, Josephine G. Ratcliffe
Row 3: Shon A. Pilarski, Julie S. Peritz, Terri L. McPherson, Tina T. chandler, Janet C. Pinkerton, Rosanna M. Knapp, Lisa A. Krukowski, Madelyn L. Nichols, Jaleh Shafii, Elizabeth A. Beer, Molly A. Finn, Dyann E. Botsford, Kathryn J. Meier, Angela L. Bruder (Crane), Herlinda Olive-Downs, Laura B. Bailey
Row 4: Laura L. Brooks, Lisa K. Feezell
Row 5: Cindy L. Harvey, Kerri A. Bacsanyi, Diane R. Cepko, Sheila E. Falk, Marylin A. Jeromin, Marianne Gerard, Sharon L. Podeszwa, Lynette A. LaPratt, Mary Ann Williams, Diana L. Faulk, Christine L. Henriksen, Sharon M. LaMacchia
Row 6: Deborah A. ranazzi (Maxim), Debra J. Mitchell, Holly B. O'Brien, Elaine K. Hebda, Jeanne L. Bruff, Crystal M. Emery, Cleola Hinton, Kathleen T. Hutton, Holly L. Nelson, Karen F. Kraker
Row 7: Meghan A. Sweeney, Christine M. Olree, Marlynn J. Marroso, Toni L. Lowery, Catherine L. Carroll, Elisabeth A. Pennington, Shake Ketefian, Rhetaugh G. Dumas, Janice B. Lindberg, Marlene Rutledge, Kimberley A. Vnuk, Anne M. Walsh, Rae Ann Vander Weide, Cheryl L. Boyd
Row 8: Renee M. Marks, Janine M. Simon, Renee A. Bowles, Linda Kurpinski-Nabozny, Teresa E. Ohman, Joanna E. Bok, Jodi F. Siegel, Janeen M. Chebli, Susan M. Williamson, Mary M. Fedewa, Rose Marie Stacey, Angela J. DeWitt, Kim E. Whelan, Lyndall P. Miller
Row 9: Jean M. Dziurgot, Amy J. Elwart, Lorrie A. Sheck, Amy A. Plasman, Mary L. Schuette, Susan K. Bowen, Heather A. Woodward, Luann N. Richert, Laurie J. Schlukebir, Linda L. Stevenson(Said), Carolyn N. Hartke, Rebecca L. Evans, Kathryn A. Savage, Kathryn A. Sailus (Linden), Heidi Deininger, Jennifer J. Eppley
Resumo:
Top Row: Clare L. Allen, Kathryn M. Antekeier, Debra Ayanian, Kristin E. Baker, Lynn A. Bluck, Linda A. Bochenek, Samatha Brennan, Julie A. Coburn, Anne E. Cooksey, Susan L. Cross, Kimberli S. Darvishian, Natalie, J. Dichtiar, Joanne M. Dork
Row 2: Mary K. Emerson, Marion A. Ferguson, Amy S. Fuhst, JAckie Vicari, Patti Geiman, Denise B. Sorenson, Lisa Maastricht, Karen L. Bloom, Natalie R. Geiss, Elizabeth A. Hamann, Liesl M. Hintermaier
Row 3: Cynthia M. Hubert, Mercedes Castro, Irene Hundt
Row 4: Kris A. Hurley, Katherine A. Jeffery, Kathy M. Jhung, Rebecca J. Kantor, Denise J. Kehrer, Colleen E. Kelly
Row 5: Judy A. Kettenstock, Rhonda L. Kinney, Kimberly Klarich, Kimberly J. Kdning, Dianne M. Kraft, Brenda M. LaChapelle
Row 6: Lavonne L. Lang, Laurie A. Langwerowski, Rebecca S. Leak, Sally Sample, Violet Barkauskas, Rhetaugh G. Dumas, Shake Ketefian, Janice B. Lindberg, Elisabeth Pennington, Sharon A. Libby, Bonnie M. McDonald, Patricia A. Mehall
Row 7: Kristen K. Miller, Kelley L. Ong, Alice I. Paik, Michelle L. Pardee, Edith H. Price, Anke Winkler-Prins, Lori L. reisig, Camille A. Rogell, Mindy A. Rosenberg, Richard E. Ross, Julie A. Sarotte, Laura A. Schippers, Rose M. Schliska, Marilyn H. Schwartz
Row 8: Heidi Simonelli, Victoria J. Sizemore, Diane L. Sorenson, Deborah R. Sproul, Katherine Stewart, Kim M. Strong, Barbara J. Sullivan, Pamela S. Taukert, Kristin A. Treash, Kimberly Vander Heuvel, Sherry Vanootighem, Annmarie Veraldi, Idella A. Wesselman
Resumo:
Top Row: Mary D. Acosta, Stephanie A. Alexovich, Lisa K. Astalos, Sandra L. Barbish, Jaine Bieda, Jennifer L. Blair, Victoria L. Brace, Debbie R. Brown, Sandra D. Carlson, Timothy J. Cockerham, Polly A. Cook, Suzanne M. Delisio, Jefferey Deloach
Row 2: Susan L. Dill, Tami Dykstra, Roberta E. Figgs, Roberta Jo Franzese, Dianer Szczerowski, Kimberly M. Schymik, Michelle F. Bingham, Lynnette A. Golen, Paola G. Pieri, Donna L. Fordanich, Teri L. Freedman, Kara L. Gathmann
Row 3: Marilyn S. Granner, Ann Marie Hartmus, Melissa Hoheb, Susan M. Hutchins
Row 4: Amy S. Jacobs, Renee M. Jannette, Wendy J. Jenuwine, Lori B. Kantor
Row 5: Kristine E. Karfis, Jenny G. Kist, Susan M. Kistka, Kaye M. Kowalske, Marilyn A. Krage, Roberta E. Kumm
Row 6: Ianya A. Lattimore, Andrea S. Lipian, Wendy J. Lipinski, Wendi M. Lisman
Row 7: Susan E. Little, Donna M. Markos, Rita S. Mayle, Lynn M. Mccall, Nancy J. Montange, Aimee J. Myers
Row 8: Clare H. Nagle, Michelle L. Noble, Janice B. Lindbers, Violet Barkauskas, Rhetaugh G. Dumas, Beverly Jones, Shake Kettfian, Elisabeth Pennington, Joyce V. Perry, Darlene L. Phelps
Row 9: Donna M. Piccolo, Lisa A. Richmond, Lisa A. Rowlison, Brent E. Runyon, Rebecca A. Seiffert, Lucinda E. Smith, Amy E. Spangler, Dan C. Steele, Beth Stephens, Kim D. Tiedrich, Lisa J. Wallace, Jennifer P. York, Christine C. Zielke
Resumo:
Top Row: Lisa A. Anton, Karen M. Banish, Sherry L. Bendele, Lori Bishop, Rossana Biundo, Jennifer Brooks, Stefanie J. Brown, Kimberly J. Coleman, Christine M. Decker, Mary Jo Diebold, Molly Donohue, Mary C. Dubois, Meggan C. Ebert
Row 2: Michelle Fox, Ann Marie Gergely, Nina N. Giglio, Stephen Gniewek, Jennifer K. Gollon, Laura E. Gregorius, Shiree A. Hamilton, Corinne R. Hardecki, Yoline M. Hargrave, Raina C. Hartitz, Dana M. Hocking, Andrea E. Jarrett
Row 3: Nancy Johnson, Harjot Kaur, Doreen M. Kinney, Kristine Boyle, Michele Phillips, Anthony Stewart, Pamela Blumson, Lisa Rudin, Lisa Eby, Christina Koehlmann, Julie A. Kolar, Shelly M. Kraiza
Row 4: Cindy Kvarnberg, Beth Anne Lannan, Martha Lasley, James A. Lowery
Row 5: Eileen M. Lucier, Anne Marie Lutostanski, Crystal Tchoryk, Kathy Kline, Donna L. Marshall, Mary C. Maxim
Row 6: Melinda J. Mc Calla, Carolyn Mclean, Molly B. Meyersohn, Christine L. Nersesian, Ann-Marie Nosotti
Row 7: Darlene D. Osemlak, Francine D. Paglia, Danee L. Paullin, Shake Ketefian, Janice B. Lindberg, Rhetaugh G. Dumas, Violet Barkauskas, Beverly Jones, Elisabeth Pennington, Jill L. Pierpont, Marie E. Rosenburg, Rebecca L. Rotole
Row 8: Carla D. Rouse, Merilynne H. Rush, Bernadette Michelle Santos, Stephanie A. Schaltz, Colleen M. Seastrom, Anita M. Shedlock, Judith A. Skonieczny, Alice Skumautz, Nancy A. Standler, Kristine Stoetzer, Annaflor O. Suan, Lynn E. Taylo
Row 9: Renee M. Thibodeau, Kirsten M. Thornquist, Lisa A. Treash, Lisa Marie Warriner, Miriam Beth Weiner, Teresa Wen, Martha Hill Wenzler, Melissa K. White, Denise M. Williams, Christina L. Wroubel, Jamie K. Yeulett, Sarah Jo York, Jennifer Zolinski
Resumo:
Top Row: Lisa M. Badalament, Heidi S. Bailey, Bonita Ballard, Betsy M. Bateman, Virginia Blackmer, Andrea L. Bonfield, Michelle L. Brown, Jane M. Christie, Gina M. Connolly, Matthew Cornell
Row 2: Mary M. Daugherty, Nancy L. Dewey, Linnette Drzewiecki, Jennifer Farah, Kelly S. Fonger, Yolanda Gardner, Kimberly A. Germain, Kelley Goetz, Laura M. Gonzalez, Melissa Gorr, Julie A. Hale, Jennifer Henstock
Row 3: Charles Houghtby III, Jennifer Hughes, Jill C. Jennings, Renee Manshardt, Jill A. Holquist, Paula R. Cowall, Kristen A. George, Michelle Ingram, Amy Jacobs
Row 4: Tara James, David Jansma, Debra A. Jorgenson, Sherry Keener
Row 5: Karen L. Kelley, Sunnah Kim, Tina Koonter-Banks, Jennifer Kratt
Row 6: Cynthia L. Lazaros, Christine Morelli, Charlotte Murphy, Sharon K. Norton
Row 7: Deborah Oliverio, Karla J. Pontier, Nicole Pruett, Laura Rankin, Jill E. Read, Diane Rosati
Row 8: Katherine E. Ross, Lisa Rubin, Lorie K. Sandberg, Violet Barkauskas, Janice Lindberg, Shake Ketefian, Elisabeth Pennington, Beverly Jones, Donita M. Shaum, Marcie S. Skinner, Julie M. Smallegan
Row 9: K. Christy Spencer, Danette L. Starr, Pamela S. Steele, Dena Stempien-Runyon, Jennifer J. Treacy, Patrica Van Maanen, Roberta Wahl, Marie A. White, Kim Wiersma, Wendy Williams, Dana Wilson
Resumo:
In this study we describe optimization of polyethylenimine (PEI)-mediated transient production of recombinant protein by CHO cells by facile manipulation of a chemically defined culture environment to limit accumulation of nonproductive cell biomass, increase the duration of recombinant protein production from transfected plasmid DNA, and increase cell-specific production. The optimal conditions for transient transfection of suspension-adapted CHO cells using branched, 25 kDa PEI as a gene delivery vehicle were experimentally determined by production of secreted alkaline phosphatase reporter in static cultures and recombinant IgG(4) monoclonal antibody (Mab) production in agitated shake flask cultures to be a DNA concentration of 1.25 mu g 10(6) cells(-1) mL(-1) at a PEI nitrogen: DNA phosphate ratio of 20:1. These conditions represented the optimal compromise between PEI cytotoxicity and product yield with most efficient recombinant DNA utilization. Separately, both addition of recombinant insulin-like growth factor (LR3-IGF) and a reduction in culture temperature to 32 degrees C were found to increase product titer 2- and 3-fold, respectively. However, mild hypothermia and LR3-IGF acted synergistically to increase product titer 11-fold. Although increased product titer in the presence of LR3-IGF alone was solely a consequence of increased culture duration, a reduction in culture temperature post-transfection increased both the integral of viable cell concentration (IVC) and cell-specific Mab production rate. For cultures maintained at 32 degrees C in the presence of LR3-IGF, IVC and qMab were increased 4- and 2.5-fold, respectively. To further increase product yield from transfected DNA, the duration of transgene expression in cell populations maintained at 32 C in the presence of LR3-IGF was doubled by periodic resuspension of transfected cells in fresh media, leading to a 3-fold increase in accumulated Mab titer from similar to 13 to similar to 39 mg L-1. Under these conditions, Mab glycosylation at Asn297 remained essentially constant and similar to that of the same Mab produced by stably transfected GS-CHO cells. From these data we suggest that the efficiency of transient production processes (protein output per rDNA input) can be significantly improved using a combination of mild hypothermia and growth factor(s) to yield an extended activated hypothermic synthesis.
Resumo:
In this study we investigate the coordination between rhythmic flexion-extension (FE) and supination-pronation (SP) movements at the elbow joint-complex, while manipulating the intersegmental dynamics by means of a 2-degrees of freedom (df) robot arm. We hypothesized that constraints imposed by the structure of the neuromuscular-skeletal system would (1) result in predominant pattern(s) of coordination in the absence of interaction torques and (2) influence the capabilities of participants to exploit artificially induced interaction torques. Two experiments were conducted in which different conditions of interaction torques were applied on the SP-axis as a function of FE movements. These conditions promoted different patterns of coordination between the 2-df. Control trials conducted in the absence of interaction torques revealed that both the in-phase (supination synchronized with flexion) and the anti-phase (pronation synchronized with flexion) patterns were spontaneously established by participants. The predominance of these patterns of coordination is explained in terms of the mechanical action of bi-articular muscles acting at the elbow joint-complex, and in terms of the reflexes that link the activity of the muscles involved. Results obtained in the different conditions of interaction torques revealed that those neuromuscular-skeletal constraints either impede or favor the exploitation of intersegmental dynamics depending on the context. Interaction torques were indeed found to be exploited to a greater extent in conditions in which the profiles of interaction torques favored one of the two predominant patterns of coordination (i.e., in-phase or anti-phase) as opposed to other patterns of coordination (e.g., 90 degrees or 270 degrees). Those results are discussed in relation to recent studies reporting exploitation of interaction torques in the context of rhythmic movements.
Resumo:
In 2009, a group of unions and social movements in Guadeloupe (a French overseas department in the Caribbean), organised a 40-day strike against 'la vie chère et la 'profitation'' (expensive life and 'profiteering'). However beyond the economic crisis, the heart of the problem were social and identity issues. This chapter analyses the political objectives and means of the organisers, as well as the answers provided by the French Government during a crisis that threatened to shake the rest of the French overseas territories.
Resumo:
Background The optimisation and scale-up of process conditions leading to high yields of recombinant proteins is an enduring bottleneck in the post-genomic sciences. Typical experiments rely on varying selected parameters through repeated rounds of trial-and-error optimisation. To rationalise this, several groups have recently adopted the 'design of experiments' (DoE) approach frequently used in industry. Studies have focused on parameters such as medium composition, nutrient feed rates and induction of expression in shake flasks or bioreactors, as well as oxygen transfer rates in micro-well plates. In this study we wanted to generate a predictive model that described small-scale screens and to test its scalability to bioreactors. Results Here we demonstrate how the use of a DoE approach in a multi-well mini-bioreactor permitted the rapid establishment of high yielding production phase conditions that could be transferred to a 7 L bioreactor. Using green fluorescent protein secreted from Pichia pastoris, we derived a predictive model of protein yield as a function of the three most commonly-varied process parameters: temperature, pH and the percentage of dissolved oxygen in the culture medium. Importantly, when yield was normalised to culture volume and density, the model was scalable from mL to L working volumes. By increasing pre-induction biomass accumulation, model-predicted yields were further improved. Yield improvement was most significant, however, on varying the fed-batch induction regime to minimise methanol accumulation so that the productivity of the culture increased throughout the whole induction period. These findings suggest the importance of matching the rate of protein production with the host metabolism. Conclusion We demonstrate how a rational, stepwise approach to recombinant protein production screens can reduce process development time.
Resumo:
We have produced human fibroblast growth factor 1 (hFGF1) in the methylotrophic yeast Pichia pastoris in order to obtain the large amounts of active protein required for subsequent functional and structural characterization. Four constructs were made to examine both intracellular and secreted expression, with variations in the location of the His6 tag at either end of the peptide. hFGF1 could be produced from all four constructs in shake flasks, but production was optimized by growing only the highest-yielding of these strains, which produced hFGF1 intracellularly, under tightly controlled conditions in a 3 L fermentor. One hundred and eight milligrams of pure protein was achieved per liter culture (corresponding to 0.68 mg of protein per gram of wet cells), the function of which was verified using NIH 3T3 cell cultures. This is a 30-fold improvement over previously reported yields of full-length hFGF1. © 2006 Elsevier Inc. All rights reserved.
Resumo:
Our understanding of the nature of competitive advantage has not been helped by a tendency for theorists to adopt a unitary position, suggesting, for example, that advantage is industry based or resource based. In examining the nature of competitive advantage in an electronic business (e-business) environment this paper adopts a contingency perspective. Several intriguing questions emerge. Do 'new economy' companies have different resource profiles to 'old economy' companies? Are the patterns of resource development and accumulation different? Are attained advantages less sustainable for e-businesses? These are the kinds of themes examined in this paper. The literature on competitive advantage is reviewed as are the challenges posed by the recent changes in the business environment.Two broad sets of firms are identified as emerging out of the e-business shake up and the resource profiles of these firms are discussed. Several research propositions are advanced and the implications for research and practice are discussed.
Resumo:
Foaming during fermentation reduces the efficiency of the process leading to increased costs and reduced productivity. Foaming can be overcome by the use of chemical antifoaming agents, however their influence upon the growth of organisms and protein yield is poorly understood. The objective of this work was to evaluate the effects of different antifoams on recombinant protein production. Antifoam A, Antifoam C, J673A, P2000 and SB2121 were tested at different concentrations for their effect on the growth characteristics of Pichia pastoris producing GFP, EPO and A2aR and the yield of protein in shake flasks over 48 h. All antifoams tested increased the total GFP in the shake flasks compared to controls, at higher concentrations than would normally be used for defoaming purposes. The highest yield was achieved by adding 1 % P2000 which nearly doubled the total yield followed by 1 % SB2121, 1 % J673A, 0.6 % Antifoam A and lastly 0.8 % Antifoam C. The antifoams had a detrimental effect upon the production of EPO and A2aR in shake flasks, suggesting that their effects may be protein specific. The mechanisms of action of the antifoams was investigated and suggested that although the volumetric mass oxygen transfer coefficient (kLa) was influenced by the agents, their effect upon the concentration of dissolved oxygen did not contribute to the changes in growth or recombinant protein yield. Findings in small scale also suggested that antifoams of different compositions such as silicone polymers and alcoxylated fatty acid esters may influence growth characteristics of host organisms and the ability of the cells to secrete recombinant protein, indirectly affecting the protein yield. Upon scale-up, the concentration effects of the antifoams upon GFP yield in bioreactors was reversed, with lower concentrations producing a higher yield. These data suggest that antifoam can affect cells in a multifactorial manner and highlights the importance of screening for optimum antifoam types and concentrations for each bioprocesses.
Resumo:
Tic-like movements in rodents bear close similarities to those observed in humans both pharmacologically and morphologically. Pharmacologically, tics are modulated by serotonergic and dopaminergic systems and abnormalities of these systems have been reported in Tourette's Syndrome (TS). Therefore, serotonergic and dopaminergic modulation of tics induced by a thyrotrophin-releasing hormone (TRH) analogue were studied as possible models for TS. The TRH analogue MK771 induced a variety of tic like movements in mice; blinking fore-paw-licking and fore-paw-tremor were quantified and serotonergic and dopaminergic modulation was investigated. The selective dopamine D1 receptor antagonists SCH23390 and SCH39166 and dopamine D2 antagonists raclopride and sulpiride had no effect on MK771 induced blinking. The D1 antagonists attenuated fore-paw-tremor and -licking while the D2 antagonists were generally without effect on these behaviours. Ketanserin (5-HT2A/ alpha-1 antagonist) and ritanserin (5-HT2A/2C antagonist) were able to attenuate MK771-induced blinking and ketanserin, mianserin (5-HT2A/2C antagonist) and prazosin (alpha-1 adrenoceptor antagonist) were able to attenuate MK771-induced fore-paw-tremor and -licking. The 5-HT2C/2B antagonist SB200646A was without effect on blinking and fore-paw-licking but dose-dependently potentiated fore-paw-tremor. The 5-HT1A agonists 8-OH DPAT and buspirone attenuated blinking at the lower doses tested but were ineffective at the higher doses; the converse was found for fore-paw-licking and -tremor behaviours.The effects of these ligands appeared to be at a postsynaptic 5-HTlA site since para-chlorophenylalanine was without effect on the manipulation of these behaviours. (S)-W A Y100135 was without effect on MK771-induced behaviours, spontaneous and DOl-induced head shakes. Because kynurenine potentiates head shakes and plasma concentrations are raised in TS patients the effects of kynurenine on the 5-HT2A/2C agonist DOl mediated head shake were established. Kynurenine potentiated the DOl head shake. Attempts were made to correlate serotonergic unit activity with tic like behaviour in cats but this proved unsuccessful. However, the pharmacological understanding of 5-HTlA receptor function has been hampered because of the lack of selective antagonists for this site. For this reason the effects of the novel 5-HTlA antagonists (S)-WA Y- 100135 and WAY -100635 were tested on 5-HT single-unit activity recorded from the dorsal-raphe-nucleus in the behaving cat. Both drugs antagonised the suppression of unit activity caused by 8-0H DPAT. (S)-WA Y-100135 reduced unit activity whereas WAY-100635 increased it. This suggests that WAY-100635 is acting as an antagonist at the 5-HTlA somatodendritic autoreceptor and that (S)W A Y -100135 acts as a partial agonist at this site. Aspects of tic like behaviour and serotonergic control are discussed.
Resumo:
The modulation of 5-hydroxytryptamine (5-HT)-related head-twitchbehaviour by antimigraine drugs and migraine triggers was examined inmice. The antimigraine drugs examined produced either inhibition or noeffect on 5-HT-related head-twitching. On the basis of these resultsit is suggested that 5-HT-related head-twitching is unlikely to beuseful in the preclinical screening and discovery of systemically-activeantimigraine agents. The migraine triggers examined, tyramineand beta-PEA initially produced a repeatable complex time-relatedeffect on 5-HT-related head-twitching, with both inhibition andpotentiation of this behaviour being observed, however, when furtherexamination of the effect of the migraine triggers on 5-HT-relatedhead-twitching was attempted some time later the effects seeninitially were no longer produced. The effect of (±)-1-<2, 5-dimethoxy-4-iodophenyl)-2-aminopropane,((±)DOl), on on-going behaviour of mice and rats was examined. Shakingbehaviour was observed in both species. In mice, excessive scratchingbehaviour was also present. (±)DOl-induced scratching and shakingbehaviour were found to be differentially modulated by noradrenergicand serotonergic agents, however, the fact that both behaviours wereblocked by ritanserin (5-HT2/5-HT1c receptor antagonist) and inhibitedby FLA-63 (a dopamine-beta-oxidase inhibitor which depletesnoradrenaline), suggests the pathways mediating these behaviours mustbe convergent in some manner, and that both behaviours require intact5-HT receptors, probably 5-HT2 receptors, for their production. Ingeneral, the behavioural profile of (±)DOI was as expected for anagent which exhibits high affinity binding to 5-HT2/5-HT1c receptors.Little sign of the 5-HTl-related '5-HT syndrome' was seen in eithermice or rats. The effect of a variety of noradrenergic agents on head-twitchinginduced by a variety of shake-inducing agents was examined. A patternof modulatory effect was seen whereby the modulatory effect of thenoradrenergic agents on 5-hydroxytryptophan <5-HTP) (and in some cases, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)) was found to be the opposite of that observed with quipazine and (±)DOI. The relationship between these effects, and their implications for understanding the pharmacology of centrally acting drugs is discussed.