Portal de Periódicos da CAPES

Abstracts of papers and posters Pharmacological Meeting

1994; Springer Science+Business Media; Volume: 16; Issue: S10 Linguagem: Inglês

10.1007/bf01870971

1573-739X

Roger A.H. Adan, John V. St. Peter, Harold J. Burbach, Willem Hendrik Gispen, Willem A. Bax, Pramod R. Saxena, Odile H.M. Beenen, M. Pfaffendorf, P. A. van Zwieten, G. Ph. Biewenga, A. J. Nicastia, Guido R.M.M. Haenen, Aalt Bast, J. Adriaan Bouwknecht, H. E. Molewijk, A. M. Der Van Poel, J. Mos, Bahuon Olivier, L. M. Broersen, Rob P.W. Heinsbroek, Jan Bruin, D. L. Brouwers, H. J. M. G. Nelissen-Vrancken, Jos F.M. Smits, T. Brüning, Michiel J. B. Kemme, Pei-Lin Chang, Y. Muizert, Theresa L. Buckley, Frans P. Nijkamp, S. L. T. Cappendijk, Shannon Duval, R. de Vries, Misa Dzoljic, J.C. Compaan, Lucianne Groenink, Jan van der Gugten, Elisabeth Cox, A. G. N. Hemert, E. de Jong, Meindert Danhof, F. R. L. Crijns, Bruce H. R. Wolffenbuttel, Helma van Essen, Harry A.J. Struijker Boudier, J. P. M. Dam, Frits N.G. Doornekamp, Evelyn Velema, Mark J. Post, C. Borst, John Y. de Boer, Herman Meurs, Antonio E. Bottone, Miranda Koopal, Jan Visser, Johan Zaagsma, Larissa M. de Lannoy, A.H.J. Danser, A. M. B. Bouhuizen, Regien G. Schoemaker, P. R. Saxena, Maarten A.D.H. Schalekamp, J. F. Vlieger, P. Wijngaard, Andries S. Koster, Theresa L. Buckley, Jaap Wilting, D. Heuven-Nolsen, Frans P. Nijkamp, Xianchao Du, Bos E, Eric A. Dubois, Rebecca Vermeulen, Alexander Janßen, Eric A. van Royen, P. J. Gaillard, Albertus G. de Boer, D. D. Breimer, Ingrid M. Garrelds, C. Graaf-in't Veld, Roy Gerth van Wijk, Freek J. Zijlstra, M.A.F.M. Gerrits, N. A. Patkina, Edwin Zvartau, Jan M. van Ree, B. C. G. Gho, P VERDOUW, M. A. Gingras, A. R. Cools, John Gommans, Theo H. Hijzen, R. A. A. Maes, P. M. Verdouw, Arnoud H. J. Herremans, Theo H. Hijzen, J. L. Slangen, Ben Hoiting, Martin Schuiling, Carolina R.S. Elzinga, Janet Hoogstraate, John Verhoef, A. H. G. J. Schrijvers, A. Pijpers, L.A.M.G. van Leengoed, J.H.M. Verheijden, H.E. Junginger, Harry E. Boddé, Birgitta C. P. Hüsken, R. J. E. Joordens, Ed A.J. Kalkman, Muzaffer Bilgin, K. L. Kam, Aletta D. Kraneveld, Thea Muis, Frans P. Nijkamp, G. S. Madretsma, A. P. M. Dijk, J. H. P. Wilson, C. M. Mohede, J Oosterhout, Frans P. Niikamp, Patrizia Nestby, D. Visser, George Wardeh, François Hogenboom, A.H. Mulder, Anton N. M. Schoffelmeer, Jan Oosting, Harry A.J. Struijker Boudier, Ben Janssen, P. C. J. J. Passier, M. J. Verluyten, H. Drexler, Mat J.A.P. Daemen, Gudarz Sadeghi Hashjin, Paul A. J. Henricks, Gert Folkerts, Mahnaz Shirmohammadi, Frans P. Niikamp, R. E. Santing, Clemens G. Olymulder, K. Molen, Heleen Scheerens, Henk Loveren, Henk Sipma, A. den Hertog, Adriaan Nelemans, J. Smit, R. P. Coppes, Eric J. J. van Tintelen, A. F. Roffel, Maaike Smit, Rob Leurs, H. Timmerman, Wiro B. Stam, C. J. J. Avezaat, Jens Stolte, Paul Schiffers, H.A.J. Struyker Boudier, R. E. J. ten Berge, Maaike Krikke, B. C. H. Teisman, Guno H.K. Tjon, N. Michiels, Paul Benjamin Voorn, P. Van Bergen, Dick J. De Wildt, D.H.G. Versteeg, M. C. Tweel, P.G.M. Bloemen, Paul A. J. Henricks, FriedrichHG Engels, F. J. E. M. Blomjous, Rick van der Geest, Teus van Laar, R. A. C. Roos, M. J. Velde, Jorge P. van Kats, L.M.A. Sassen, Michele Polak, F. H. M. Derkx, Catharina A. M. van Kesteren, Jos M. J. Lamers, Han A. A. Van Heugten, N.L.U. van Meeteren, A. Frankhuyzen-Sierevogel, Jan H. Brakkee, V. M. Wiegant, W.H. Gispen, Margreeth B. Vroom, Harry B. van Wezel, Erik J.F. Timmenga, Chantal M.A.M. van der Horst, E. A. Winkler Prins, J. Zwavelina, Angela H.E.M. Maas, J. Zhang, J. Zwaveling, Frank Jansen, Takatoshi Mochizuki, A Yamatodani, Rosalinde Masereeuw, W. M. Moons, Frans G. M. Rüssel, Hendrik van de Meent, C. Berg, J. Wemer, W. Vleeming, C. M. Kasbergen, E.M. van der Aa, A. C. Wouterse, J.H.J. Copius Peereboom‐Stegeman, E. M. Hessel, A. J. M. van Oosterhout, Joris J. De Bie, G.A. Hofman, Henk Loveren,

Metanocortins have various physiological actions on the brain.The recent cloning of neural melanecortin 0//(2) receptors Opened new avenues to study the effect of these ncuropeptides on the nervous system.We investigated the structure activity relations (SARs) of peptides derived from adrenecorticotropo hormone (ACrH) on cloned MC3, MC4 and MC5 receptors in vitro.Analysis of the effects of various melanocortin peptides on cAMP accumulation in and on binding to cells that expressed either the rat MC3 receptor, the human MC4 receptor or the ovine MC5 receptor demonstrated that different ACTH fragments and analogs could selectively activate or inhibit the MC receptor subtype activities.The SAP.. of the MC4 receptor resembled that of the induction of excessive grooming behavior by melanocortin poptides.Antagonists that blocked the MC4 receptor were also tested to block a behavioral response induced by cc-MSH, a-MSH-induced excessive grooming behavi~ in rats was inhibited by [Pbe-IT]ACTH-(4-10), [D-ArgS]ACTH-(4-10) and [ProSa~ but not by [Ala6]ACTH-(4-10).From these 4 antagonists, only the latter compound did not antagonize the MC4 receptor in vitro.Therefore, we suggest that this behavioral response is mediated by MC4 receptors.ORG2766, an ACTH 4-9 analog that is very potent in an active avoidance task, did not activate, antagonize or bind to the MC receptors.This suggests the presence of still other MC receptors than the MC3, MC4 and MC5 receptors in the brain.In order to develop more selective MC (an0agonists, the interaction of melanoeortins and receptors at molecular level were investigated.Based upon a 3D-medel for MC receptors and the differences in primary ,structure of the MC receptors, receptormutagenesis was preformed in order to identify the amino acids in the receptors that underly the selectivity that these receptors display for the different melanecortins.Therefore, the MC4 receptor, which is not activated by low doses of yMSH, was genetically modified with sequences that occur in the MC3 receptor, which is activated by yMSH.Furthermore, amino acids that according to our model were important for peptide binding were mutated.Both the binding characteristics as well as the activation of the mutated MC4 receptors by melanecorims were altered.These studies may be employed for development of novel MC-receptor-spectfie ligands.