Involvement of calcitonin gene-related peptide (CGRP) and nitric oxide (NO) in the pial artery dilatation elicited by cortical spreading depression

1994 ◽  
Vol 637 (1-2) ◽  
pp. 204-210 ◽  
Author(s):  
M. Wahl ◽  
L. Schilling ◽  
A.A. Parsons ◽  
A. Kaumann
Keyword(s):  
Nitric Oxide ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Pial Artery ◽  
Calcitonin Gene

Calcitonin gene-related peptide promotes cerebrovascular dilation during cortical spreading depression in rabbits

1994 ◽  
Vol 266 (3) ◽  
pp. H1095-H1102 ◽  
Author(s):  
D. M. Colonna ◽  
W. Meng ◽  
D. D. Deal ◽  
D. W. Busija
Keyword(s):  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Topical Administration ◽  
Competitive Inhibitor ◽  
Calcitonin Gene Related Peptide ◽  
Cranial Window ◽  
Related Peptide ◽  
Brain Surface ◽  
Calcitonin Gene ◽  
Pial Arterioles

We examined the role of calcitonin gene-related peptide (CGRP) in cortical spreading depression (CSD)-induced dilation of rabbit pial arterioles. In urethan-anesthetized rabbits instrumented with a closed cranial window, CSD induction with KCl dilated pial arterioles from 86 +/- 10 to 132 +/- 13 (mean +/- SE, n = 6) microns (a 54 +/- 9% increase). Topical administration of 12.8 microM CGRP-(8-37), a competitive inhibitor of the CGRP receptor, reduced CSD-induced pial dilation from 54 +/- 9% baseline to 33 +/- 9% (P < 0.05). Removal of the receptor antagonist from the brain surface restored CSD-induced dilation to 59 +/- 11% (P < 0.05, compared with the response with the antagonist present). In other animals, we showed that this dose of the CGRP antagonist attenuated arteriolar dilation to topically applied 10(-7) M CGRP (n = 5), but it did not alter arteriolar dilation to arterial hypercapnia. We also evaluated the dilator potency of substance P (SP) compared with CGRP. Dilation with 10(-7) M SP was only 22 +/- 11%, whereas arterioles dilated to 57 +/- 7% above baseline diameter with 10(-7) M CGRP. We conclude that CGRP contributes to the transient arteriolar dilation that is characteristic of CSD.

Cortical Spreading Depression Does Not Result in the Release of Calcitonin Gene-Related Peptide into the External Jugular Vein of the Cat: Relevance to Human Migraine

Cephalalgia ◽  
1993 ◽  
Vol 13 (3) ◽  
pp. 180-183 ◽  
Author(s):  
Richard D Piper ◽  
Lars Edvinsson ◽  
Rolf Ekman ◽  
Geoffrey A Lambert
Keyword(s):  
Migraine With Aura ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Jugular Vein ◽  
Calcitonin Gene Related Peptide ◽  
External Jugular Vein ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Vasoactive Peptide ◽  
Stimulation Of

There is circumstantial evidence that cortical spreading depression (SD) may account for the scotoma and the “spreading cortical oligemia” seen during migraine with aura. It has been shown that calcitonin gene-related peptide (CGRP) is increased in blood taken from the external jugular vein (EJV) in humans during migraine and after stimulation of the trigeminal ganglion. To test the hypothesis that cortical SD may elevate the concentration of this vasoactive peptide in the EJV during migraine, we have measured its concentration in the external jugular vein of cats during cortical SD. This study demonstrates that SD has no effect on the concentration of CGRP either during the passage of a wave of spreading depression across the cortex or, 60 min later, during the period of post-SD cortical oligemia.

scholarly journals Induction of calcitonin gene-related peptide expression in rats by cortical spreading depression

Cephalalgia ◽  
2016 ◽  
Vol 39 (3) ◽  
pp. 333-341 ◽  
Author(s):  
Yan Wang ◽  
Anne E Tye ◽  
Junli Zhao ◽  
Dongqing Ma ◽  
Ann C Raddant ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Calcitonin Gene Related Peptide ◽  
Rat Cerebral Cortex ◽  
Mrna Levels ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Peptide Expression ◽  
Cortical Regions

Objective The neuropeptide calcitonin gene-related peptide (CGRP) has now been established as a key player in migraine. However, the mechanisms underlying the reported elevation of CGRP in the serum and cerebrospinal fluid of some migraineurs are not known. A candidate mechanism is cortical spreading depression (CSD), which is associated with migraine with aura and traumatic brain injury. The aim of this study was to investigate whether CGRP gene expression may be induced by experimental CSD in the rat cerebral cortex. Methods CSD was induced by topical application of KCl and monitored using electrophysiological methods. Quantitative PCR and ELISA were used to measure CGRP mRNA and peptide levels in discrete ipsilateral and contralateral cortical regions of the rat brain 24 hours following CSD events and compared with sham treatments. Results The data show that multiple, but not single, CSD events significantly increase CGRP mRNA levels at 24 hours post-CSD in the ipsilateral rat cerebral cortex. Increased CGRP was observed in the ipsilateral frontal, motor, somatosensory, and visual cortices, but not the cingulate cortex, or contralateral cortices. CSD also induced CGRP peptide expression in the ipsilateral, but not contralateral, cortex. Conclusions Repeated CSD provides a mechanism for prolonged elevation of CGRP in the cerebral cortex, which may contribute to migraine and post-traumatic headache.

scholarly journals Cortical spreading depression as a site of origin for migraine: Role of CGRP

Cephalalgia ◽  
2018 ◽  
Vol 39 (3) ◽  
pp. 428-434 ◽  
Author(s):  
Liesl N Close ◽  
Sajedeh Eftekhari ◽  
Minyan Wang ◽  
Andrew C Charles ◽  
Andrew F Russo
Keyword(s):  
Cortical Neurons ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Calcitonin Gene Related Peptide ◽  
Trigeminal System ◽  
Migraine Treatment ◽  
Neural Connections ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
A Site

Premise Migraine is a complex neurologic disorder that leads to significant disability, yet remains poorly understood. Problem One potential triggering mechanism in migraine with aura is cortical spreading depression, which can activate the trigeminal nociceptive system both peripherally and centrally in animal models. A primary neuropeptide of the trigeminal system is calcitonin gene-related peptide, which is a potent vasodilatory peptide and is currently a major therapeutic target for migraine treatment. Despite the importance of both cortical spreading depression and calcitonin gene-related peptide in migraine, the relationship between these two players has been relatively unexplored. However, recent data suggest several potential vascular and neural connections between calcitonin gene-related peptide and cortical spreading depression. Conclusion This review will outline calcitonin gene-related peptide-cortical spreading depression connections and propose a model in which cortical spreading depression and calcitonin gene-related peptide act at the intersection of the vasculature and cortical neurons, and thus contribute to migraine pathophysiology.

Involvement of calcitonin gene-related peptide in control of human fetoplacental vascular tone

2004 ◽  
Vol 286 (1) ◽  
pp. H230-H239 ◽  
Author(s):  
Yuan-Lin Dong ◽  
Sujatha Vegiraju ◽  
Madhu Chauhan ◽  
Pandu R. R. Gangula ◽  
Gary D. V. Hankins ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Human Placenta ◽  
Vascular Tone ◽  
Umbilical Artery ◽  
Force Measurement ◽  
Isometric Force ◽  
Calcitonin Gene Related Peptide ◽  
Immunofluorescent Staining ◽  
Related Peptide ◽  
Calcitonin Gene

Calcitonin gene-related peptide (CGRP), one of the most potent endogenous vasodilators known, has been implicated in vascular adaptations and placental functions during pregnancy. The present study was designed to examine the existence of CGRP-A receptor components, the calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1), in the human placenta and the vasoactivity of CGRP in the fetoplacental circulation. Immunofluorescent staining of the human placenta in term labor using polyclonal anti-CRLR and RAMP1 antibodies revealed that labeling specifically concentrated in the vascular endothelium and the underlying smooth muscle cells in the umbilical artery/vein, chorionic artery/vein, and stem villous vessels as well as in the trophoblast layer of the placental villi. In vitro isometric force measurement showed that CGRP dose dependently relaxes the umbilical artery/vein, chorionic artery/vein, and stem villous vessels. Furthermore, CGRP-induced relaxation of placental vessels are inhibited by a CGRP receptor antagonist (CGRP8–37), ATP-sensitive potassium (KATP) channel blocker (glybenclamide), and cAMP-dependent protein kinase A inhibitor (Rp-cAMPS) and partially inhibited by a nitric oxide inhibitor ( Nω-nitro-l-arginine methyl ester). We propose that CGRP may play a role in the control of human fetoplacental vascular tone, and the vascular dilations in response to CGRP may involve activation of KATP channels, cAMP, and a nitric oxide pathway.

Sign in / Sign up

Export Citation Format

Share Document