Vasodilation by calcitonin gene-related peptide (CGRP) and by transmural stimulation of the methoxamine-contracted rat hepatic artery after pre treatment with guanethidine

From this study, we predicted that the human calcitonin gene-related peptide (hCGRP) fragment hCGRP-(8-37) would be a selective antagonist for CGRP receptors but an agonist for calcitonin (CT) receptors. In rat liver plasma membrane, where CGRP receptors predominate and CT appears to act through these receptors, hCGRP-(8-37) dose dependently displaced 125I-[Tyr0]rat CGRP binding. However, hCGRP-(8-37) had no effect on adenylate cyclase activity in liver plasma membrane. Furthermore, hCGRP-(8-37) inhibited adenylate cyclase activation induced not only by hCGRP but also by hCT. On the other hand, in LLC-PK1 cells, where calcitonin receptors are abundant and CGRP appears to act via these receptors, the bindings of 125I-[Tyr0]rat CGRP and 125I-hCT were both inhibited by hCGRP-(8-37). In contrast to liver membranes, interaction of hCGRP-(8-37) with these receptors led to stimulation of adenosine 3',5'-cyclic monophosphate (cAMP) production in LLC-PK1 cells, and moreover, this fragment did not inhibit the increased production of cAMP induced not only by hCT but also by hCGRP. Thus hCGRP-(8-37) appears to be a useful tool for determining whether the action of CGRP as well as that of CT is mediated via specific CGRP receptors or CT receptors.

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Stimulation of acetylcholine release in myenteric plexus by calcitonin gene-related peptide

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1990.259.6.g934 ◽

1990 ◽

Vol 259 (6) ◽

pp. G934-G939 ◽

Cited By ~ 1

Author(s):

M. W. Mulholland ◽

S. Jaffer

Keyword(s):

Myenteric Plexus ◽

Acetylcholine Release ◽

Calcitonin Gene Related Peptide ◽

Ach Release ◽

Related Peptide ◽

Calcitonin Gene ◽

Dose Dependent Increase ◽

Dose Dependent ◽

Dependent Mechanism ◽

Stimulation Of

The effects of calcitonin gene-related peptide (CGRP) on acetylcholine (ACh) release from myenteric plexus neurons in primary culture were investigated. CGRP (10(-12) to 10(-6) M) produced a dose-dependent increase in [3H]ACh release. The ACh release caused by CGRP was significantly inhibited (74 +/- 24%) by preincubation with dideoxyadenosine but was increased more than threefold by preincubation with theophylline. Incubation of myenteric plexus neurons with CGRP (10(-8) M) in the presence of diltiazem (10(-5) M) or in a calcium-free medium markedly reduced [3H]ACh release. CGRP potentiated [3H]ACh release stimulated by potassium or substance P but not by cholecystokinin octapeptide or forskolin. The results demonstrate that CGRP cause release of ACh from guinea pig myenteric plexus neurons and suggest that the peptide acts through an adenosine 3',5'-cyclic monophosphate-dependent mechanism that involves neuronal calcium channels.

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Effect of a calcitonin gene-related peptide antagonist (CGRP8-37) on skin vasodilatation and oedema induced by stimulation of the rat saphenous nerve

British Journal of Pharmacology ◽

10.1111/j.1476-5381.1993.tb13878.x ◽

1993 ◽

Vol 110 (2) ◽

pp. 772-776 ◽

Cited By ~ 91

Author(s):

K. Jane Escott ◽

Susan D. Brain

Keyword(s):

Calcitonin Gene Related Peptide ◽

Saphenous Nerve ◽

Related Peptide ◽

Calcitonin Gene ◽

Peptide Antagonist ◽

Stimulation Of

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Nitric oxide synthase, calcitonin gene-related peptide and NK-1 receptor mechanisms are involved in GTN-induced neuronal activation

Cephalalgia ◽

10.1177/0333102413502735 ◽

2013 ◽

Vol 34 (2) ◽

pp. 136-147 ◽

Cited By ~ 48

Author(s):

Roshni Ramachandran ◽

Deepak Kumar Bhatt ◽

Kenneth Beri Ploug ◽

Anders Hay-Schmidt ◽

Inger Jansen-Olesen ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Femoral Vein ◽

Calcitonin Gene Related Peptide ◽

Human Model ◽

Neuronal Activation ◽

Related Peptide ◽

Calcitonin Gene ◽

Pre Treatment ◽

Oxide Synthase

Background and aim Infusion of glyceryltrinitrate (GTN), a nitric oxide (NO) donor, in awake, freely moving rats closely mimics a universally accepted human model of migraine and responds to sumatriptan treatment. Here we analyse the effect of nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP) systems on the GTN-induced neuronal activation in this model. Materials and methods The femoral vein was catheterised in rats and GTN was infused (4 µg/kg/min, for 20 minutes, intravenously). Immunohistochemistry was performed to analyse Fos, nNOS and CGRP and Western blot for measuring nNOS protein expression. The effect of olcegepant, L-nitro-arginine methyl ester (L-NAME) and neurokinin (NK)-1 receptor antagonist L-733060 were analysed on Fos activation. Results GTN-treated rats showed a significant increase of nNOS and CGRP in dura mater and CGRP in the trigeminal nucleus caudalis (TNC). Upregulation of Fos was observed in TNC four hours after the infusion. This activation was inhibited by pre-treatment with olcegepant. Pre-treatment with L-NAME and L-733060 also significantly inhibited GTN induced Fos expression. Conclusion The present study indicates that blockers of CGRP, NOS and NK-1 receptors all inhibit GTN induced Fos activation. These findings also predict that pre-treatment with olcegepant may be a better option than post-treatment to study its inhibitory effect in GTN migraine models.

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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 ◽

10.1046/j.1468-2982.1993.1303180.x ◽

1993 ◽

Vol 13 (3) ◽

pp. 180-183 ◽

Cited By ~ 29

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.

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