Rutaecarpine alleviates acute pancreatitis in mice and AR42J cells by suppressing the MAPK and NF‐κB signaling pathways via calcitonin gene‐related peptide

2021 ◽  
Author(s):  
Haosu Huang ◽  
Meng Wang ◽  
Zimeng Guo ◽  
Di Wu ◽  
Hanyue Wang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Signaling Pathways ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Ar42j Cells ◽  
Calcitonin Gene

Investigation of distinct molecular pathways in migraine induction using calcitonin gene-related peptide and sildenafil

Cephalalgia ◽  
2019 ◽  
Vol 39 (14) ◽  
pp. 1776-1788 ◽  
Author(s):  
Samaira Younis ◽  
Casper E Christensen ◽  
Nikolaj M Toft ◽  
Thomas Søborg ◽  
Faisal M Amin ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Calcitonin Gene Related Peptide ◽  
Guanosine Monophosphate ◽  
Related Peptide ◽  
Intracellular Signaling Pathways ◽  
Calcitonin Gene

Objective Migraine displays clinical heterogeneity of attack features and attack triggers. The question is whether this heterogeneity is explained by distinct intracellular signaling pathways leading to attacks with distinct clinical features. One well-known migraine-inducing pathway is mediated by cyclic adenosine monophosphate and another by cyclic guanosine monophosphate. Calcitonin gene-related peptide triggers migraine via the cyclic adenosine monophosphate pathway and sildenafil via the cyclic guanosine monophosphate pathway. To date, no studies have examined whether migraine induction mediated via the cyclic adenosine monophosphate and cyclic guanosine monophosphate pathways yields similar attacks within the same patients. Methods Patients were subjected to migraine induction on two separate days using calcitonin gene-related peptide (1.5 µg/min for 20 minutes) and sildenafil (100 mg) in a double-blind, randomized, double-dummy, cross-over design. Data on headache intensity, characteristics and accompanying symptoms were collected until 24 hours after drug administration. Results Thirty-four patients were enrolled and 27 completed both study days. Seventeen patients developed migraine after both study drugs (63%; 95% CI: 42–81). Eight patients developed migraine on one day only (seven after sildenafil and one after calcitonin gene-related peptide). Two patients did not develop migraine on either day. Headache laterality, nausea, photophobia and phonophobia were similar between drugs in 77%, 65%, 100%, and 94%, respectively, of the 17 patients who developed attacks on both days. Conclusion A majority of patients developed migraine after both calcitonin gene-related peptide and sildenafil. This supports the hypothesis that the cyclic adenosine monophosphate and cyclic guanosine monophosphate intracellular signaling pathways in migraine induction converge in a common cellular determinator, which ultimately triggers the same attacks. Trial registration: ClinicalTrials.gov Identifier: NCT03143465.

Calcitonin gene-related peptide elevates calcium and polarizes membrane potential in MG-63 cells by both cAMP-independent and -dependent mechanisms

2004 ◽  
Vol 287 (2) ◽  
pp. C457-C467 ◽  
Author(s):  
Douglas M. Burns ◽  
Lisa Stehno-Bittel ◽  
Tomoyuki Kawase
Keyword(s):  
Membrane Potential ◽  
Signaling Pathways ◽  
Secondary Phase ◽  
Calcitonin Gene Related Peptide ◽  
Published Data ◽  
Maximal Effect ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Intracellular Ca ◽  
20 Nm

Published data suggest that the neuropeptide calcitonin gene-related peptide (CGRP) can stimulate osteoblastic bone formation; however, interest has focused on activation of cAMP-dependent signaling pathways in osteogenic cells without full consideration of the importance of cAMP-independent signaling. We have now examined the effects of CGRP on intracellular Ca2+ concentration ([Ca2+]int) and membrane potential ( Em) in preosteoblastic human MG-63 cells by single-cell fluorescent confocal analysis using fluo 4-AM-fura red-AM and bis(1,3-dibarbituric acid)-trimethine oxanol [DiBAC4( 3 )] bis-oxonol assays. CGRP produced a two-stage change in [Ca2+]int: a rapid transient peak and a secondary sustained increase. Both responses were dose dependent with an EC50 of ∼0.30 nM, and the maximal effect (initially ∼3-fold over basal levels) was observed at 20 nM. The initial phase was sensitive to inhibition of Ca2+ mobilization with thapsigargin, whereas the secondary phase was eliminated only by blocking transmembrane Ca2+ influx with verapamil or inhibiting cAMP-dependent signaling with the Rp isomer of adenosine 3′,5′-cyclic monophosphorothioate (Rp-cAMPS). These data suggest that CGRP initially stimulates Ca2+ discharge from intracellular stores by a cAMP-independent mechanism and subsequently stimulates Ca2+ influx through L-type voltage-dependent Ca2+ channels by a cAMP-dependent mechanism. In addition, CGRP dose-dependently polarized cellular Em, with maximal effect at 20 nM and an EC50 of 0.30 nM. This effect was attenuated with charybdotoxin (−20%) or glyburide (glibenclamide; −80%), suggesting that Em hyperpolarization is induced by both Ca2+-activated and ATP-sensitive K+ channels. Thus CGRP signals strongly by both cAMP-dependent and cAMP-independent signaling pathways in preosteoblastic human MG-63 cells.

Serotonin, calcitonin and calcitonin gene-related peptide in acute pancreatitis

2017 ◽  
Vol 52 (10) ◽  
pp. 1140-1147
Author(s):  
Kirsten Lykke Wahlstrøm ◽  
Srdan Novovic ◽  
Annette Kjær Ersbøll ◽  
Philip Hasbak ◽  
Lars Nannestad Jørgensen ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene

The Relationship between Trypsin/Calcitonin Gene Related Peptide (CGRP) in Serum and Acute Pancreatitis (AP)

2018 ◽  
Vol 64 (01+02/2018) ◽  
Author(s):  
Jianxiong Hu ◽  
Wei Lin ◽  
Chengfei Zhao ◽  
Jianfang Chen
Keyword(s):  
Acute Pancreatitis ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
The Relationship

scholarly journals Experimental colitis triggers the release of substance P and calcitonin gene-related peptide in the urinary bladder via TRPV1 signaling pathways

2010 ◽  
Vol 225 (2) ◽  
pp. 262-273 ◽  
Author(s):  
Xiao-Qing Pan ◽  
Jessica A. Gonzalez ◽  
Shaohua Chang ◽  
Samuel Chacko ◽  
Alan J. Wein ◽  
...  
Keyword(s):  
Substance P ◽  
Urinary Bladder ◽  
Signaling Pathways ◽  
Experimental Colitis ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene

scholarly journals Influence of calcitonin gene-related peptide on model mice with acute pancreatitis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jianxiong Hu ◽  
Yanya Lin ◽  
Shijun Chen ◽  
Yangfang Cai ◽  
Zhiwei Chen ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Blood Flow ◽  
B Lymphocytes ◽  
Intraperitoneal Injection ◽  
Calcitonin Gene Related Peptide ◽  
Pancreatic Tissue ◽  
Pancreatic Acinar Cells ◽  
Inflammatory Infiltration ◽  
Related Peptide ◽  
Calcitonin Gene

Abstract Objectives To establish model mice with acute pancreatitis (AP) and study influence of calcitonin gene-related peptide (CGRP) on AP. Methods The model mice with AP were firstly established by intraperitoneal injection of successive six doses of caerulein (100 μg/kg) and one dose of lipopolysaccharide (10 mg/kg). The intraperitoneal injection of CGRP (100 μg/kg) was performed to investigate influence of CGRP on AP, mainly involving the determination of amylase activity and the expression of CGRP and CD20+ B lymphocytes. Results CGRP on mice with AP could significantly reduce the severity of pancreatic pathological injury, the activity of amylase and the expression of CD20+ B lymphocytes. CGRP was significantly expressed in pancreatic tissue with AP, but CGRP receptor antagonist down-regulated the expression of CGRP and increased the number of CD20+ B lymphocytes, confirming the protective effect of CGRP on pancreatic tissue. Conclusions We preliminarily conclude that CGRP could significantly improve the pancreatic lesions and inflammatory infiltration of pancreas in mice with AP, and reduce the damage of pancreatic acinar cells, by mainly increasing blood flow and blood flow velocity of pancreas to improve the pancreatic microcirculation and effectively reducing the permeability of the microvessels to decrease the pathological damage degree of AP.

scholarly journals Signaling pathways that mediate nerve growth factor-induced increase in expression and release of calcitonin gene-related peptide from sensory neurons

Neuroscience ◽  
2010 ◽  
Vol 171 (3) ◽  
pp. 910-923 ◽  
Author(s):  
K.A. Park ◽  
J.C. Fehrenbacher ◽  
E.L. Thompson ◽  
D.B. Duarte ◽  
C.M. Hingtgen ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Sensory Neurons ◽  
Calcitonin Gene Related Peptide ◽  
Nerve Growth ◽  
Related Peptide ◽  
Calcitonin Gene
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