Structural Determinants in the Calcitonin Receptor-Like Receptor (Crlr) Important for Cgrp and Adrenomedullin (Am) Receptor Function of Crlr/Receptor-Activity-Modifying Protein (Ramp) 1 and Crlr/Ramp2 Heterodimers

Cell surface protein cross-linking, coimmmunoprecipitation, and confocal microscopy identified CRLR/RAMP1-, CRLR/RAMP2-, and calcitonin receptor isotype 2 (CTR2)/RAMP1 heterodimers as CGRP-, AM-, and CGRP/amylin receptors, linked to cAMP production. Along these lines, effects of structural alterations in the N-terminal extracellular domain of the human CRLR on cell surface expression as well as the association with RAMP and CGRP or AM have been investigated

Update on the pharmacology of calcitonin/CGRP family of peptides:IUPHAR Review 25

The calcitonin/calcitonin gene-related peptide (CGRP) family of peptides includes calcitonin, α and β CGRP, amylin, adrenomedullin (AM) and adrenomedullin 2/intermedin (AM2/IMD). Their receptors consist of one of two G protein-coupled receptors (GPCRs), the calcitonin receptor (CTR) or the calcitonin receptor-like receptor (CLR). Further diversity arises from heterodimerisation of these GPCRs with one of three receptor activity-modifying proteins (RAMPs). This gives the CGRP receptor (CLR/RAMP1), the AM1 and AM2 receptors (CLR/RAMP2 or RAMP3) and the AMY1, AMY2 and AMY3 receptors (CTR/RAMPs1-3 complexes, respectively). Apart from the CGRP receptor, there are only peptide antagonists widely available for these receptors and these have limited selectivity, thus defining the function of each receptor in vivo remains challenging. Further challenges arise from the probable co-expression of CTR with the CTR/RAMP complexes and species-dependent splice variants of the CTR (CT(a) and CT(b)). Furthermore, the AMY1(a) receptor is activated equally well by both amylin and CGRP and the preferred receptor for AM2/IMD has been unclear. However, there are clear therapeutic rationales for developing agents against the various receptors for these peptides. For example many agents targeting the CGRP system are in clinical trials and pramlintide, an amylin analogue, is an approved therapy for insulin-requiring diabetes. This review provides an update on the pharmacology of the calcitonin family of peptides by members of the corresponding subcommittee of the International Union of Basic and Clinical Pharmacology and colleagues

Responding to civilian bloodshed: Investigating the relationship between one-sided violence and aid

Do foreign aid flows respond to signals of need? This thesis explores the potential relationship between one-sided violence and foreign aid donations. I argue that one-sided violence operates as a signal to the international community, indicating that a state is in need of aid. Utilizing foreign aid as a means of understanding international response, I execute a series of empirical tests to establish if such a relationship can be confirmed. While conclusive determination of the relationship was not obtained, I provide the foundations for future avenues of research for one-sided violence and foreign aid

Responding to civilian bloodshed: Investigating the relationship between one-sided violence and aid

Do foreign aid flows respond to signals of need? This thesis explores the potential relationship between one-sided violence and foreign aid donations. I argue that one-sided violence operates as a signal to the international community, indicating that a state is in need of aid. Utilizing foreign aid as a means of understanding international response, I execute a series of empirical tests to establish if such a relationship can be confirmed. While conclusive determination of the relationship was not obtained, I provide the foundations for future avenues of research for one-sided violence and foreign aid.</p

Architecture in the 20th Century

+287hlm.;26c