The Calcitonin Gene Related Peptide Family
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The Calcitonin Gene Related Peptide Family
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Author : Deborah L. Hay
language : en
Publisher: Springer Science & Business Media
Release Date : 2009-10-03
The Calcitonin Gene Related Peptide Family written by Deborah L. Hay and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-10-03 with Medical categories.
In 1925, J. B. Collip (1925) reported that extracts of parathyroid gland contained an activity that raised calcium levels in the blood of parathyroidectomized animals, and suggested that this was due to a hormone produced in the parathyroid gland. The story of parathyroid hormone discovery was indicative of ever-increasing sophistication in sample preparation and protein isolation techniques. This paper resolved earlier controversies over the function of the parathyroid glands and c- trol of blood calcium. The year 1961 was a banner year for parathyroid research, in which the peptides parathyroid hormone and calcitonin were purified, and in which it was suggested that calcitonin could lower blood calcium (Copp and Cameron 1961). In 1982 it was discovered that in neurons the primary RNA transcript for calcitonin could be alternatively-spliced to give calcitonin gene-reated peptide (CGRP), and shortly thereafter amylin (previously named islet amyloid polyp- tide, IAPP) was identified and shown to have homology to CGRP. Since then a and b CGRP have been delineated and adrenomedullin and intermedin discovered, and this family of homologous peptides has emerged. This family of peptide hormones has a diverse and constantly expanding range of important physiologic functions, including regulation of blood calcium, vascular tension, feeding behavior and pain recognition.
The Cgrp Family
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Author : David Poyner
language : en
Publisher: CRC Press
Release Date : 1999-10-01
The Cgrp Family written by David Poyner and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999-10-01 with Science categories.
This book is based on presentations given at CGRP '98, the Third International Meeting on CGRP and related peptides held in the UK in May 1998. The principal speakers have each contributed a chapter and many of the short and poster communications will also be found here. This book follows from the tradition set by the First and Second Meetings in 1
The Calcitonin Gene Related Peptide Family
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Author : Deborah L. Hay
language : en
Publisher:
Release Date : 2009-10-04
The Calcitonin Gene Related Peptide Family written by Deborah L. Hay and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-10-04 with MEDICAL categories.
The Calcitonin Gene Related Peptide Family
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Author : Deborah L. Hay
language : en
Publisher: Springer
Release Date : 2009-10-14
The Calcitonin Gene Related Peptide Family written by Deborah L. Hay and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-10-14 with Medical categories.
In 1925, J. B. Collip (1925) reported that extracts of parathyroid gland contained an activity that raised calcium levels in the blood of parathyroidectomized animals, and suggested that this was due to a hormone produced in the parathyroid gland. The story of parathyroid hormone discovery was indicative of ever-increasing sophistication in sample preparation and protein isolation techniques. This paper resolved earlier controversies over the function of the parathyroid glands and c- trol of blood calcium. The year 1961 was a banner year for parathyroid research, in which the peptides parathyroid hormone and calcitonin were purified, and in which it was suggested that calcitonin could lower blood calcium (Copp and Cameron 1961). In 1982 it was discovered that in neurons the primary RNA transcript for calcitonin could be alternatively-spliced to give calcitonin gene-reated peptide (CGRP), and shortly thereafter amylin (previously named islet amyloid polyp- tide, IAPP) was identified and shown to have homology to CGRP. Since then a and b CGRP have been delineated and adrenomedullin and intermedin discovered, and this family of homologous peptides has emerged. This family of peptide hormones has a diverse and constantly expanding range of important physiologic functions, including regulation of blood calcium, vascular tension, feeding behavior and pain recognition.
The Cgrp Family
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Author : David Poyner
language : en
Publisher: R. G. Landes
Release Date : 2000
The Cgrp Family written by David Poyner and has been published by R. G. Landes this book supported file pdf, txt, epub, kindle and other format this book has been release on 2000 with Adrenomedullin categories.
Sites Of Interaction Between Calcitonin Family Peptides And Their Receptors
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Author : Tao Qi
language : en
Publisher:
Release Date : 2011
Sites Of Interaction Between Calcitonin Family Peptides And Their Receptors written by Tao Qi and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with Amylin categories.
"The calcitonin-family of peptides comprises calcitonin, amylin, calcitonin gene-related peptides (CGRPs), adrenomedullin (AM) and AM2. Their receptors are calcitonin receptorlike receptor (CLR) or calcitonin receptor (CTR) and receptor activity-modifying protein (RAMP) complexes. RAMP1 with CLR constitutes the CGRP receptor whereas RAMP2 or 3 with CLR generates the AM receptors. Amylin receptors are formed from CTR interactions with RAMPs. The association of RAMPs with CLR or CTR can alter receptor trafficking, pharmacology or/and signalling capabilities. Despite the broad pharmacological potential as drug targets for treatments of diseases such as diabetes, migraine and osteoporosis, the calcitonin peptide family receptors are not fully characterised. This is mainly due to the difficulty in the structural determination and the complexity of the interaction system. To generate drugs that target these receptors, a clearer understanding of the role of each receptor component in peptide binding is needed. In the thesis, structure-function relationships of residues or regions in the extracellular N termini of RAMPs were determined aiming to identify residues or regions that are important for ligand to receptor interactions for the calcitonin family peptides. The data generated have emphasised the importance of helices 2 and 3 of RAMP to peptide to receptor interactions. In particular, E74 of RAMP3 has been demonstrated to be crucial for high affinity binding and high potency response of AM at the AM2 receptor. In addition, a naturally occurring variant of the human CTR lacking the N-terminal 47 amino acids has been characterised in this thesis. For the first time, it has been shown that this truncated variant is still able to form a functional amlyin receptor with RAMP1 at the cell surface. The observation of reduced potency for some peptide ligands at the truncated CTR suggests that the truncated region may contain some residues that are involved in the interactions for these peptides. In summary, the findings in this thesis have contributed to our understanding of the ligand to receptor interactions for the calcitonin family peptides. Residues and regions identified in this thesis could potentially provide some targeting points for future investigations for rational drug design"--Abstract.
Calcitonin Gene Related Peptide Cgrp Novel Biology And Treatments
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Author : Susan D. Brain
language : en
Publisher: Frontiers Media SA
Release Date : 2022-08-17
Calcitonin Gene Related Peptide Cgrp Novel Biology And Treatments written by Susan D. Brain and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-08-17 with Science categories.
Development Of Cgrp Receptor Peptide Antagonists As Potential Therapeutics
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Author : Aqfan Jamaluddin
language : en
Publisher:
Release Date : 2020
Development Of Cgrp Receptor Peptide Antagonists As Potential Therapeutics written by Aqfan Jamaluddin and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020 with Calcitonin gene-related peptide categories.
Calcitonin gene-related peptide (CGRP) is a 37 amino-acid neuropeptide that initiates intracellular signalling through binding and activation of a group of calcitonin-family class B G protein-coupled receptors (GPCR). The canonical receptor for CGRP is the heteromeric CGRP receptor, comprised of the calcitonin receptor-like receptor (CLR) in complex with receptor activity-modifying protein 1 (RAMP1). CGRP is primarily expressed in nociceptive sensory neurons that innervate peripheral tissues. CGRP displays pleiotropic biological effects that include vasodilation, inflammation, pain transmission and energy homeostasis. As CGRP activity is implicated in a variety of dysregulated conditions, the development of therapeutics that modulate or block CGRP action is an active area of research. The first developed small molecule antagonists such as olcegepant and telcagepant displayed nanomolar affinity but were discontinued due to poor oral bioavailability and liver toxicity issues respectively. However, this set the stage for the development of more successful CGRP inhibitors such as the monoclonal antibody -ubrogepant. At present, several humanised monoclonal antibodies such as erenumab and fremanezumab have shown clinical efficacy for migraine treatment and are approved by the FDA as therapeutics. Another potential therapeutic strategy is to develop peptides to block CGRP action. However, peptides typically have short half-life in vivo, which limits their utility as therapeutics for clinical use. To counteract this drawback, modifications such as lipidation can be employed to extend peptide half-life. This thesis focuses on CGRP8-37, which is a truncated form of CGRP lacking the first seven residues. CGRP8-37 is a competitive antagonist at both CGRP and Amylin 1 (AMY1) receptors, which is also responsive to CGRP. The aim was to investigate the pharmacology and biological action of lipidated analogues based on CGRP8-37 to ascertain their therapeutic potential as peptide-based antagonists of CGRP action. Chapter 3 investigates the antagonist activities of several cysteine-substituted and palmitoylated analogues based on CGRP8-37 or CGRP7-37 across several calcitonin-family receptors expressed in transiently transfected Cos-7 cells. Chapter 4 describes further characterisation of the analogues’ antagonist activities at CGRP and AMY1 receptors as well as the CGRP receptor endogenously expressed in SK-N-MC cells. Chapter 5 describes the establishment and validation of a Laser doppler technique to investigate vasodilatory action by endogenous CGRP release in vivo. Selected lipidated peptide antagonists were investigated for their ability to attenuate this response and therefore discern its CGRP antagonist activity in vivo. Findings show that palmitoylation improved antagonist activity across both CGRP and AMY1 receptors, as well as several other calcitonin family receptors. The antagonist activity of the lipidated peptides exhibited hemi-equilibrium characteristics suggesting altered binding kinetics. The lipidated peptide analogues, V8C-palmitate and K24C-palmitate, were tested in vivo and showed inhibition of CGRP action as measured through suppression of capsaicin-induced dermal vasodilatory responses in mice. Overall, these findings support lipidation as a viable option to develop CGRP peptide antagonists as potential therapeutics.
Monoclonal Antibodies In Headache
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Author : Antoinette Maassen van den Brink
language : en
Publisher: Springer Nature
Release Date : 2021-04-28
Monoclonal Antibodies In Headache written by Antoinette Maassen van den Brink and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-04-28 with Medical categories.
Intended to promote a more appropriate and modern therapeutic approach to migraine management, this book is the first to deal with monoclonal antibodies in this context. Authored by the most respected migraine experts from around the globe and drawing on the lessons learned in both clinical trials and clinical practice, it reviews the current state of knowledge on this important therapeutic innovation, which has produced impressive data in randomized controlled trials, and the efficacy and safety of which have been confirmed in day-to-day real-world use. Given its scope, the book will appeal to a broad range of specialists, including pharmacologists, clinical pharmacologists, neurologists and internists, but also to residents and medical students.
The Chemistry And Biology Of Nitroxyl Hno
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Author : Fabio Doctorovich
language : en
Publisher: Elsevier
Release Date : 2016-09-01
The Chemistry And Biology Of Nitroxyl Hno written by Fabio Doctorovich and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-09-01 with Science categories.
The Chemistry and Biology of Nitroxyl (HNO) provides first-of-its-kind coverage of the intriguing biologically active molecule called nitroxyl, or azanone per IUPAC nomenclature, which has been traditionally elusive due to its intrinsically high reactivity. This useful resource provides the scientific basis to understand the chemistry, biology, and technical aspects needed to deal with HNO. Building on two decades of nitric oxide and nitroxyl research, the editors and authors have created an indispensable guide for investigators across a wide variety of areas of chemistry (inorganic, organic, organometallic, biochemistry, physical, and analytical); biology (molecular, cellular, physiological, and enzymology); pharmacy; and medicine. This book begins by exploring the unique molecule’s structure and reactivity, including important reactions with small molecules, thiols, porphyrins, and key proteins, before discussing chemical and biological sources of nitroxyl. Advanced chapters discuss methods for both trapping and detecting nitroxyl by spectroscopy, electrochemistry, and fluorescent inorganic cellular probing. Expanding on the compound’s foundational chemistry, this book then explores its molecular physiology to offer insight into its biological implications, pharmacological effects, and practical issues. Presents the first book on HNO (nitroxyl or azanone), an increasingly important molecule in biochemistry and pharmaceutical research Provides a valuable coverage of HNO’s chemical structure and significant reactions, including practical guidance on working with this highly reactive molecule Contains high quality content from recognized experts in both industry and academia