Nitroxyl (HNO), a one-electron-reduced form of nitric oxide, has various biological activities, including a cardioprotective effect. Here, we first synthesized another, more hydrophilic photocontrollable HNO donor (3), which can release HNO in a spatially and temporally controlled manner, and then examined the properties of our series of compounds as practical HNO donors in a cellular system un...

Few studies have investigated the role calcitonin gene-related peptide (CGRP) plays in the process of spinal fusion. The aim of the present study is to observe the temporal and spatial changes of CGRP induced by experimental fusion surgery in rats and elucidate the role of CGRP in spinal fusion. Male Sprague-Dawley rats were used in the study and the specimens were collected on the 7th, 14th, 2...

1 Dodick DW, Goadsby PJ, Spierings ELH, Scherer JC, Sweeney SP, Grayzel DS. Safety and effi cacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study Lancet Neurol 2014; published online Aug 11. http://dx.doi.org/10.1016/S1474-4422(14)70128-0. 2 Goadsby PJ, Edvinsson L, Ekman R. Rele...

The present study investigated the role of calcitonin gene-related peptide (CGRP) on nociception in nucleus raphe magnus (NRM) and the interaction between CGRP and opioid peptides in NRM of rats. CGRP-like immunoreactivity was found at a concentration of 6.0+/-0. 77 pmol/g in NRM tissue of ten samples of rats, suggesting that it may contribute to physiological responses orchestrated by the NRM....

A highly efficient, asymmetric synthesis of telcagepant (1), a CGRP receptor antagonist for the treatment of migraine, is described. This synthesis features the first application of iminium organocatalysis on an industrial scale. The key to the success of this organocatalytic transformation was the identification of a dual acid cocatalyst system, which allowed striking a balance of the reaction...

of the Dissertation xi Chapter 1: Introduction 1 Chapter 2: PDF receptor preferentially couples to AC3 in small LNv cells in Drosophlia 22 Chapter 3: PDF receptor signalosome components vary between pacemaker subgroups 61 Chapter 4: Daily changes in PDF receptor signaling 83 Chapter 5: DH81 is a potent activator of the CGRP receptor encoded by CG4395 108

Osteoarthritis (OA) pain is poorly understood and managed, as current analgesics have only limited efficacy and unwanted side effect profiles. A broader understanding of the pathological mechanisms driving OA joint pain is vital for the development of improved analgesics. Both clinical and preclinical data suggest an association between joint levels of the sensory neuropeptide calcitonin gene-r...

Introduction: Migraine is a highly devastating neurovascular disorder that affects up to 16% of the population worldwide. In spite of intensive research, its origin remains enigmatic with no therapeutic option appropriate for all migraine patients. One of the leading hypotheses is related to the function of the calcitonin gene-related peptide (CGRP). Regardless, the pharmaceutical options curre...

Recent findings CGRP is widely distributed in the nervous system, particularly at anatomical areas thought to be involved with migraine, including the trigeminovascular nociceptive system. In studies, CGRP has been shown to be released during severe migraine attacks, and effective triptan treatment of an attack normalizes these levels. CGRP administration triggers migraine in patients and CGRP ...

Calcitonin gene related peptide immunoreactivity was investigated in the rat lung. Immunoreactive material was observed in nerve fibres surrounding bronchi, bronchioli, and blood vessels, and also in neuroendocrine cells and neuroepithelial bodies. In addition, the peptide was identified by immunoelectron microscopy in dense cored vesicles of granulated cells of the neuroepithelial bodies. Thes...