Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Background Calcitonin gene-related peptide (CGRP) is a neuropeptide that acts in the trigeminovascular system and is believed to play an important role in migraine. CGRP activates two receptors that are both present in the trigeminovascular system; the CGRP receptor and the amylin 1 (AMY1) receptor. CGRP receptor antagonists, including olcegepant (BIBN4096BS) and telcagepant (MK-0974), can treat migraine. This study aimed to determine the effectiveness of these antagonists at blocking CGRP receptor signalling in trigeminal ganglia (TG) neurons and transfected CGRP and AMY1 receptors in Cos7 cells, to better understand their mechanism of action. Methods CGRP stimulation of four intracellular signalling molecules relevant to pain (cAMP, CREB, p38 and ERK) were examined in rat TG neurons and compared to transfected CGRP and AMY1 receptors in Cos7 cells. Results In TG neurons, olcegepant displayed signal-specific differences in antagonism of CGRP responses. This effect was also evident in transfected Cos7 cells, where olcegepant blocked CREB phosphorylation more potently than expected at the AMY1 receptor, suggesting that the affinity of this antagonist can be dependent on the signalling pathway activated. Conclusions CGRP receptor antagonist activity appears to be assay-dependent. Thus, these molecules may not be as selective for the CGRP receptor as commonly reported.
Cephalalgia 2018 03
PMID:CGRP receptor antagonist activity of olcegepant depends on the signalling pathway measured. 2816 87

The calcitonin gene-related peptide (CGRP) neuropeptide system is an important but still evolving target for migraine. A fundamental consideration for all of the current drugs in clinical trials and for ongoing development in this area is the identity, expression pattern, and function of CGRP receptors because this knowledge informs safety and efficacy considerations. In recent years, only the calcitonin receptor-like receptor/receptor activity-modifying protein 1 (RAMP1) complex, known as the CGRP receptor, has generally been considered relevant. However, CGRP is capable of activating multiple receptors and could have more than one endogenous receptor. The recent identification of the CGRP-responsive calcitonin receptor/RAMP1 complex (AMY1 receptor - amylin subtype 1 receptor) in the trigeminovascular system warrants a deeper consideration of the molecular identity of CGRP receptor(s) involved in the pathophysiology, and thus potential treatment of migraine. This perspective considers some of the issues and implications.
Headache 2017 Apr
PMID:CGRP and its receptors. 2836 96

Amylin is a 37 amino acid peptide hormone that is closely related to calcitonin gene-related peptide (CGRP). Amylin and CGRP share a receptor and are reported to have several similar biological actions. Given the important role of CGRP in migraine and intense efforts to develop drugs against this target, it is important to consider potential areas of overlap between the amylin and CGRP systems. This short review provides a brief introduction to amylin biology, the use of an amylin analog to treat diabetes, and consideration of whether amylin could have any role in headache disorders. Finally, this review informs readers about the AMY1 (amylin subtype 1) receptor, which is a dual receptor for amylin and CGRP and potentially plays a role in the bioactivity of both of these peptides.
Headache 2017 May
PMID:Amylin. 2848 43

The calcitonin gene-related peptide (CGRP) family of neuropeptides, consists of CGRP, adrenomedullin, amylin, and calcitonin. The receptors consist of either calcitonin receptor-like receptor (CLR) or calcitonin receptor (CTR) which for function needs an accessory protein, receptor activity-modifying proteins (RAMPs). CGRP has a pivotal role in primary headaches but the role of the other members of the CGRP family of peptides in headaches is not known. Here, we describe the expression of these molecules in the trigeminal ganglion (TG) to understand more on their possible role(s). Single or double immunohistochemistry were applied on frozen sections of rat TG using primary antibodies against CGRP, procalcitonin, calcitonin, adrenomedullin, amylin, RAMP1/2/3, CLR, and CTR. In addition, mRNA expression was measured by quantitative qPCR on TGs. CGRP and calcitonin showed rich expression in the cytoplasm of small to medium-sized neurons, and co-localized sometimes. Procalcitonin was observed in the glial cells. Immunoreactive fibers storing both CGRP and calcitonin were also observed. Adrenomedullin immunoreactivity was found in the satellite glial cells and in fibers, probably the myelinating Schwann cells. Amylin was found in the cytoplasm in many TG neurons. Levels of mRNA expression for adrenomedullin, amylin, CLR, RAMP1, RAMP2, RAMP3, and CTR were measured using qPCR. The experiments verified the expression of mRNA in the TG with the exception of CTR, which was above the limit of detection indicating little or no mRNA expression. In addition to the well-known CGRP receptor (CLR/RAMP1) and the receptor for calcitonin-CTR, we propose that other receptors exist in the rat TG: adrenomedullin receptor AM2 (CLR/RAMP3) in mainly the satellite glial cells, amylin receptors AMY1 (CTR/RAMP1) in mainly neurons, and AMY3 (CTR/RAMP3) in the satellite glial cells. It is important to compare peptides and receptors side-by-side in studies to help address questions of actions resulting from cross-reactivity between receptors. Several of the diverse biological actions of the CGRP family of peptides are clinically relevant. Our findings demonstrate the specific ligand and receptor sites in the rat trigeminal ganglion, highlighting recognition mechanisms to facilitate drug development.
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PMID:Expression of the CGRP Family of Neuropeptides and their Receptors in the Trigeminal Ganglion. 3208 79