The origin of circulating calcitonin gene-related peptide in the rat

1986 ◽  
Vol 110 (1) ◽  
pp. 185-190 ◽  
Author(s):  
M. Zaidi ◽  
P. J. R. Bevis ◽  
G. Abeyasekera ◽  
S. I. Girgis ◽  
S. J. Wimalawansa ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Potent Vasodilator ◽  
Perivascular Nerves ◽  
Old Rats ◽  
Different Sources

ABSTRACT It is known that in addition to the calcitonin precursor the calcitonin gene also encodes a novel peptide, calcitonin gene-related peptide (CGRP). This potent vasodilator has been found in the circulation of man. This present study demonstrates that CGRP is also found in the circulation of the rat and that plasma CGRP comes from two different sources: the thyroid, a major source in old rats, and the perivascular nerves probably at all ages. J. Endocr. (1986) 110, 185–190

scholarly journals Role of Calcitonin Gene Related Peptide (CGRP) in Migraine

2017 ◽  
Vol 33 (1) ◽  
pp. 39-43
Author(s):  
Md Ashraf Ali ◽  
Habibur Rahaman
Keyword(s):  
Family Relationships ◽  
Preventive Treatment ◽  
Primary Headache ◽  
Calcitonin Gene Related Peptide ◽  
Childhood And Adolescence ◽  
Protein Extravasation ◽  
Related Peptide ◽  
Plasma Protein Extravasation ◽  
Calcitonin Gene ◽  
Potent Vasodilator

Migraine is the second most primary headache. The prevalence of Migraine is 12% in the general population, including 18% in women and 6% in men. Migraine can start in childhood and adolescence and continue throughout lifespan. It is most prevalent among people in their 30s and 40s. Migraine is a debilitating hemicranial headache that is pulsating, aggravated by movement, nausea, vomiting and having sensitivity to light and sound, with or without aura. It can affect all aspects of life as work and school, parenting and family relationships and personal and leisure time. There are some theory regarding pathogenesis of migraine which includes cortical spreading depression, cortical spreading oligemia, activation of trigeminocervical complex leading to neuroinflammation & release of vasodialating neuropeptides which include calcitonin gene related peptide (CGRP), substance P, vasoactive intestinal polypeptide (VIP), nitric oxide (NO), and pituitary adenylate cyclase activating peptide (PACAP) & genetic factor. CGRP is a potent vasodilator and causes perivascular plasma protein extravasation and nociceptive pain. Newer medications target CGRP both for acute and preventive treatment of migraine. Bangladesh Journal of Neuroscience 2017; Vol.  33 (1): 39-43

scholarly journals Acetaminophen (Paracetamol) Metabolites Induce Vasodilation and Hypotension by Activating Kv7 Potassium Channels Directly and Indirectly

2020 ◽  
Vol 40 (5) ◽  
pp. 1207-1219 ◽  
Author(s):  
Jennifer van der Horst ◽  
Rian W. Manville ◽  
Katie Hayes ◽  
Morten B. Thomsen ◽  
Geoffrey W. Abbott ◽  
...  
Keyword(s):  
Preventive Intervention ◽  
Ex Vivo ◽  
Calcitonin Gene Related Peptide ◽  
Mesenteric Arteries ◽  
Benzoquinone Imine ◽  
Kv7 Channels ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Perivascular Nerves ◽  
Life Threatening

Objective: Intravenous acetaminophen/paracetamol (APAP) is well documented to cause hypotension. Since the patients receiving intravenous APAP are usually critically ill, any severe hemodynamic changes, as with those associated with APAP, can be life-threatening. The mechanism underlying this dangerous iatrogenic effect of APAP was unknown. Approach and Results: Here, we show that intravenous APAP caused transient hypotension in rats, which was attenuated by the Kv7 channel blocker, linopirdine. APAP metabolite N-acetyl-p-benzoquinone imine caused vasodilatation of rat mesenteric arteries ex vivo. This vasodilatation was sensitive to linopirdine and also the calcitonin gene-related peptide antagonist, BIBN 4096. Further investigation revealed N-acetyl-p-benzoquinone imine stimulates calcitonin gene-related peptide release from perivascular nerves, causing a cAMP-dependent activation of Kv7 channels. We also show that N-acetyl-p-benzoquinone imine enhances Kv7.4 and Kv7.5 channels overexpressed in oocytes, suggesting that it can activate Kv7.4 and Kv7.5 channels directly, to elicit vasodilatation. Conclusions: Direct and indirect activation of Kv7 channels by the APAP metabolite N-acetyl-p-benzoquinone imine decreases arterial tone, which can lead to a drop in blood pressure. Our findings provide a molecular mechanism and potential preventive intervention for the clinical phenomenon of intravenous APAP-dependent transient hypotension.

Human calcitonin gene related peptide: a potent endogenous vasodilator in man

1986 ◽  
Vol 70 (4) ◽  
pp. 389-393 ◽  
Author(s):  
A. D. Struthers ◽  
M. J. Brown ◽  
D. W. R. Macdonald ◽  
J. L. Beacham ◽  
J. C. Stevenson ◽  
...  
Keyword(s):  
Diastolic Pressure ◽  
Normal Subjects ◽  
Calcitonin Gene Related Peptide ◽  
Plasma Calcium ◽  
Human Calcitonin ◽  
High Concentration ◽  
Plasma Adrenaline ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Perivascular Nerves

1. In addition to calcitonin and katacalcin, it is now known that the human calcitonin gene encodes a novel peptide called calcitonin gene related peptide (CGRP). In experimental animals, CGRP produces vasodilatation and complex changes in plasma calcium. 2. We have now assessed its biological activity in man by infusing human CGRP (hCGRP) into six normal volunteers. hCGRP (545 pmol/min) caused the diastolic pressure to fall from 64 ± 5 to 55 ± 7mmHg (P < 0.05), the heart rate to increase from 61 ± 7 to 87 ± 5 beats/min (P < 0.05) and the skin temperature to increase from 33.7 ± 0.9 to 34.9 ± 0.5°C. Plasma noradrenaline increased from 481 ± 126 to 835 ± 65 pg/ml (P < 0.05) and plasma adrenaline from 57 ± 17 to 82 ± 12 pg/ml (P < 0.05). There were no significant changes in the albumin-corrected plasma calcium. 3. hCGRP is thus a potent endogenous vasodilator in man and is in fact more potent than any other known vasodilator. Together with the observations that CGRP circulates in normal subjects at relatively high concentration (approximately 25 pmol/l) and that CGRP is present in perivascular nerves, this study suggests a possible role for CGRP in controlling peripheral vascular tone in man.

Effect of chronic sensory denervation on Ca2+-induced relaxation of isolated mesenteric resistance arteries

1998 ◽  
Vol 274 (5) ◽  
pp. H1655-H1661 ◽  
Author(s):  
Maria M. Mupanomunda ◽  
Yanlin Wang ◽  
Richard D. Bukoski
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Relaxation Response ◽  
Resistance Arteries ◽  
Related Peptide ◽  
Density Control ◽  
Calcitonin Gene ◽  
Perivascular Nerves ◽  
Sensory Denervation ◽  
Immunocytochemical Studies ◽  
Dose Dependent

We recently reported that Ca2+-induced relaxation could be linked to a Ca2+ receptor (CaR) present in perivascular nerves. The present study assessed the effect of chronic sensory denervation on Ca2+-induced relaxation. Mesenteric resistance arteries were isolated from rats treated as neonates with capsaicin (50 mg/kg), vehicle, or saline. The effect of cumulative addition of Ca2+ was assessed in vessels precontracted with 5 μM norepinephrine. Immunocytochemical studies showed that capsaicin treatment significantly reduced the density of nerves staining positively for calcitonin gene-related peptide (CGRP) and for the CaR (CGRP density: control, 51.1 ± 3.9 μm2/mm2; capsaicin treated, 31.4 ± 2.8 μm2/mm2, P = 0.01; control CaR density, 46 ± 4 μm2/mm2, n = 7; capsaicin-treated CaR density, 24 ± 4 μm2/mm2, n = 8, P = 0.002). Dose-dependent relaxation to Ca2+ (1–5 mM) was significantly depressed in vessels from capsaicin-treated rats (overall P < 0.001, n = 6 or 7), whereas the relaxation response to acetylcholine remained intact. These data support the hypothesis that Ca2+-induced relaxation is mediated by activation of the CaR associated with capsaicin-sensitive perivascular neurons.

scholarly journals Release of calcitonin gene-related peptide (CGRP) from perivascular nerves in the rat mesenteric artery

1989 ◽  
Vol 49 ◽  
pp. 244
Author(s):  
Akira Fujimori ◽  
Akira Saito ◽  
Sadao Kimura ◽  
Yasuo Uchiyama ◽  
Hiromu Kawasaki ◽  
...  
Keyword(s):  
Mesenteric Artery ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Rat Mesenteric Artery ◽  
Perivascular Nerves

Calcitonin gene-related peptide is a potent vasodilator

Nature ◽  
1985 ◽  
Vol 313 (5997) ◽  
pp. 54-56 ◽  
Author(s):  
S. D. Brain ◽  
T. J. Williams ◽  
J. R. Tippins ◽  
H. R. Morris ◽  
I. MacIntyre
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Potent Vasodilator

scholarly journals Calcitonin Gene-Related Peptide: Physiology and Pathophysiology

2014 ◽  
Vol 94 (4) ◽  
pp. 1099-1142 ◽  
Author(s):  
F. A. Russell ◽  
R. King ◽  
S.-J. Smillie ◽  
X. Kodji ◽  
S. D. Brain
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Sensory Nerves ◽  
Therapeutic Area ◽  
Protective Mechanisms ◽  
Related Peptide ◽  
Pain Pathways ◽  
Calcitonin Gene ◽  
Potent Vasodilator ◽  
Skin Conditions ◽  
Diabetes And Obesity

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide. Discovered 30 years ago, it is produced as a consequence of alternative RNA processing of the calcitonin gene. CGRP has two major forms (α and β). It belongs to a group of peptides that all act on an unusual receptor family. These receptors consist of calcitonin receptor-like receptor (CLR) linked to an essential receptor activity modifying protein (RAMP) that is necessary for full functionality. CGRP is a highly potent vasodilator and, partly as a consequence, possesses protective mechanisms that are important for physiological and pathological conditions involving the cardiovascular system and wound healing. CGRP is primarily released from sensory nerves and thus is implicated in pain pathways. The proven ability of CGRP antagonists to alleviate migraine has been of most interest in terms of drug development, and knowledge to date concerning this potential therapeutic area is discussed. Other areas covered, where there is less information known on CGRP, include arthritis, skin conditions, diabetes, and obesity. It is concluded that CGRP is an important peptide in mammalian biology, but it is too early at present to know if new medicines for disease treatment will emerge from our knowledge concerning this molecule.

CALCITONIN GENE-RELATED PEPTIDE: POTENT VASODILATOR AND MAJOR PRODUCT OF CALCITONIN GENE

The Lancet ◽  
1985 ◽  
Vol 326 (8445) ◽  
pp. 14-16 ◽  
Author(s):  
SamiaI. Girgis ◽  
JohnC. Stevenson ◽  
Catherine Lynch ◽  
ColinH. Self ◽  
DavidW.R. Macdonald ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Major Product ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Potent Vasodilator
Sign in / Sign up

Export Citation Format

Share Document