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Many Peptides (many + peptide)
Selected AbstractsPeptide signaling paths related to intoxication, memory and addictionADDICTION BIOLOGY, Issue 3 2000William E. M. Lands Many peptides bind to G protein-coupled receptors and activate intracellular signaling paths for adaptive cellular responses. The components of these paths can be affected by signals from other neurotransmitters to produce overall integrated results not easily predicted from customary a priori considerations. This intracellular cross-talk among signaling paths provides a "filter" through which long-term tonic signals affect short-term phasic signals as they progress toward the nucleus and induce long-term adaptation of gene expression which provide enduring attributes of acquired memories and addictions. Peptides of the PACAP family provide intracellular signaling that involves kinases, scaffolding interactions, Ca2 + mobilization, and gene expression to facilitate development of tolerance to alcohol and development of associative memories. The peptide-induced enhancement of NMDA receptor responses to extracellular glutamate also may increase behavioral sensitization to the low doses of alcohol that occur at the onset of each bout of drinking. Because many gene products participate in each signaling path, each behavioral response to alcohol is a polygenic process of many steps with no single gene product sufficient to interpret fully the adaptive response to alcohol. Different susceptibility of individuals to alcohol addiction may be a cumulative result of small differences among the many signaling components. Understanding this network of signals may help interpret future "magic bullets" proposed to treat addiction. [source] Mast cells, peptides and cardioprotection , an unlikely marriage?AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2009S. K. Walsh Summary 1,Mast cells have classically been regarded as the ,bad guys' in the setting of acute myocardial ischaemia, where their released contents are believed to contribute both to tissue injury and electrical disturbances resulting from ischaemia. Recent evidence suggests, however, that if mast cell degranulation occurs in advance of ischaemia onset, this may be cardioprotective by virtue of the depletion of mast cell contents that can no longer act as instruments of injury when the tissue becomes ischaemic. 2,Many peptides, such as ET-1, adrenomedullin, relaxin and atrial natriuretic peptide, have been demonstrated to be cardioprotective when given prior to the onset of myocardial ischaemia, although their physiological functions are varied and the mechanisms of their cardioprotective actions appear to be diverse and often ill defined. However, one common denominator that is emerging is the ability of these peptides to modulate mast cell degranulation, raising the possibility that peptide-induced mast cell degranulation or stabilization may hold the key to a common mechanism of their cardioprotection. 3,The aim of this review was to consolidate the evidence implying that mast cell degranulation could play both a detrimental and protective role in myocardial ischaemia, depending upon when it occurs, and that this may underlie the cardioprotective effects of a range of diverse peptides that exerts physiological effects within the cardiovascular system. [source] Blood group antigens and immune responses,detailed knowledge is necessary to prevent immunization and to follow up immunized individualsISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue n1 2010A. Husebekk Background The immune system is educated to detect and react with foreign antigens and to tolerate self-antigen. Transfusion of blood cells and plasma and pregnancies challenge the immune system by the introduction of foreign antigens. The antigens may cause an immune response, but in many instances this is not the case and the individual is not immunised after exposure of blood group antigens. Aims The aim of the presentation is to dissect some immune responses to blood group antigens in order to understand the mechanism of immunisation. Methods The results of immune responses to blood group antigens can be detected by the presence of antibodies to the antigens. If the antibodies are of IgG class, the activated B cells have received help from antigen specific T cells. Both antibodies, B cells and T cells can be isolated from immunised individuals and studied in the laboratory. Also B-cell receptors and T-cell receptors as well as MHC molecules on antigen presenting cells can be studied and models of the immune synapses can be created in vitro. Results The most classic immune responses in transfusion medicine and in incompatible pregnancies are immune responses to the RhD antigen on red cells, HLA class I molecules on white cells and platelets and human platelet antigens. The nature of these antigens are different; RhD antigens are part of a large complex, present on red cells from RhD positive individuals and completely lacking on red cells from RhD negative individuals. It is likely that many peptides derived from this antigen complex may stimulate T cells and B cells. HLA antigens are highly polymorphic and the antigens are known to induce strong alloimmune responses. The HPA antigens are created by one amino acid difference in allotypes based on a single nucleotide polymorphism at the genetic level. HPA 1a induce immune responses in 10% of HPA 1b homozygote pregnant women. The result of these immune responses is destruction of blood cells with clinical consequences connected to the effect of transfusions or the outcome of pregnancies. Summary/Conclusions Even though there is emerging knowledge about the immune responses to some of the blood group antigens, more information must be gained in order to understand the complete picture. The action of the innate immune response initiating the adaptive immune response to blood group antigens is not well understood. A detailed understanding of both the innate ad the adaptive part of the immune response is necessary to identify individuals at risk for immunisation and to prevent immunisation to blood group antigens. [source] Studies on the cellular uptake of substance P and lysine-rich, KLA-derived model peptides,JOURNAL OF MOLECULAR RECOGNITION, Issue 1 2005Johannes Oehlke Abstract In the last decade many peptides have been shown to be internalized into various cell types by different, poorly characterized mechanisms. This review focuses on uptake studies with substance P (SP) aimed at unravelling the mechanism of peptide-induced mast cell degranulation, and on the characterization of the cellular uptake of designed KLA-derived model peptides. Studies on structure,activity relationships and receptor autoradiography failed to detect specific peptide receptors for the undecapeptide SP on mast cells. In view of these findings, a direct interaction of cationic peptides with heterotrimeric G proteins without the participation of a receptor has been proposed. Such a process would require insertion into and translocation of peptides across the plasma membrane. In order to clarify whether a transport of cationic peptides into rat peritoneal mast cells is possible, transport studies were performed by confocal laser scanning microscopy (CLSM) using fluorescence-labeled Arg3,Orn7 -SP and its D -amino acid analog, all- D -Arg3,Orn7 -SP, as well as by electron microscopic autoradiography using 3H-labelled SP and 125I-labelled all- D -SP. The results obtained by CLSM directly showed translocation of SP peptides into pertussis toxin-treated cells. Kinetic experiments indicated that the translocation process was rapid, occurring within a few seconds. Mast cell degranulation induced by analog of magainin 2 amide, neuropeptide Y and the model peptide acetyl-KLALKLALKALKAALKLA-amide was also found to be very fast, pointing to an extensive translocation of the peptides. In order to learn more about structural requirements for the cellular uptake of peptides, the translocation behavior of a set of systematically modified KLA-based model peptides has been studied in detail. By two different protocols for determining the amount of internalized peptide, evidence was found that the structure of the peptides only marginally affects their uptake, whereas the efflux of cationic, amphipathic peptides is strikingly diminished, thus allowing their enrichment within the cells. Although the mechanism of cellular uptake, consisting of energy-dependent and -independent contributions, is not well understood, KLA-derived peptides have been shown to deliver various cargos (PNAs, peptides) into cells. The results obtained with SP- and KLA-derived peptides are discussed in the context of the current literature. Copyright © 2004 John Wiley & Sons, Ltd. [source] Improving pharmacokinetic properties of adrenocorticotropin by site-specific lipid modificationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2003Lei Wan Abstract Although many peptides are potentially good therapeutic agents for treating various diseases, only a few have been developed for limited applications. A major shortcoming is that peptides have generally very short serum half lives. In the present study, we use adrenocorticotropin (ACTH) as a model and explore the potential of combining site-specific amino acid substitution and lipid modification to increase the circulating half-lives of peptides. Phe39 of ACTH was substituted by Cys, which has a free sulfhydryl group that can react specifically with iodoacetamide derivatives of lipophilic groups. The biological activities of lipophilized ACTH(F39C)s were higher than native ACTH. Lipophilized ACTH(F39C)s bound more tightly to human serum albumin and cell membranes in vitro and had longer serum half-lives in vivo than native ACTH. These results indicate that the pharmacokinetic properties of peptides can be improved by site-specific substitution with cysteine residues and subsequent conjugation with lipophilic moieties. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:1882,1892, 2003 [source] | |||||||||||||