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.

scholarly journals Calcitonin gene-related peptide receptor antagonist human CGRP-(8-37)

1989 ◽  
Vol 256 (2) ◽  
pp. E331-E335 ◽  
Author(s):  
T. Chiba ◽  
A. Yamaguchi ◽  
T. Yamatani ◽  
A. Nakamura ◽  
T. Morishita ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Adenylate Cyclase ◽  
Calcitonin Gene Related Peptide ◽  
Human Calcitonin ◽  
Liver Plasma Membrane ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Liver Membranes ◽  
Calcitonin Receptors ◽  
Stimulation Of

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.

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.

The myotropic and plasma-calcium modulating effects of calcitonin gene-related peptide (CGRP)

Neuropeptides ◽  
1984 ◽  
Vol 4 (5) ◽  
pp. 425-434 ◽  
Author(s):  
J.R. Tippins ◽  
H.R. Morris ◽  
M. Panico ◽  
T. Etienne ◽  
P. Bevis ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Plasma Calcium ◽  
Related Peptide ◽  
Calcitonin Gene

scholarly journals Alternative RNA processing events in human calcitonin/calcitonin gene-related peptide gene expression.

1985 ◽  
Vol 82 (7) ◽  
pp. 1994-1998 ◽  
Author(s):  
V. Jonas ◽  
C. R. Lin ◽  
E. Kawashima ◽  
D. Semon ◽  
L. W. Swanson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Processing ◽  
Calcitonin Gene Related Peptide ◽  
Human Calcitonin ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Peptide Gene

scholarly journals Cross-reactivity of amylin with calcitonin-gene-related peptide binding sites in rat liver and skeletal muscle membranes

1991 ◽  
Vol 277 (1) ◽  
pp. 139-143 ◽  
Author(s):  
A Chantry ◽  
B Leighton ◽  
A J Day
Keyword(s):  
Skeletal Muscle ◽  
Binding Site ◽  
Rat Liver ◽  
Specific Binding ◽  
Calcitonin Gene Related Peptide ◽  
Cross Reactivity ◽  
Scatchard Analysis ◽  
Human Calcitonin ◽  
Related Peptide ◽  
Calcitonin Gene

This study examines whether the high degree of sequence identity between amylin and calcitonin-gene-related peptide (CGRP) is reflected in their cross-reactivity at the level of membrane receptor binding. Rat liver plasma membranes contain a specific saturable binding site for 125I-labelled human CGRP-1. Binding reached equilibrium within 30 min and was rapidly reversed by re-incubating membranes in the presence of 1 microM human CGRP. In addition, the presence of 50 mM- or 500 mM-NaCl lowered specific binding by 30% and 77% respectively. Scatchard analysis was consistent with a single high-affinity site with a dissociation constant (Kd) of 0.125 nM and binding capacity (Bmax.) of 580 fmol/mg of membrane protein. Specific binding of 125I-labelled human CGRP-1 to both liver and skeletal muscle membranes was inhibited by human CGRP-1 [IC50 (concn. causing half-maximal inhibition of binding) 0.1-0.3 nM], and rat amylin (IC50 10 nM), but not by human calcitonin. Covalent cross-linking of 125I-CGRP to its binding site in rat skeletal muscle and liver membranes resulted in labelling of a major species of about 70 kDa under reducing conditions and about 55 kDa under alkylating conditions, as visualized on SDS/PAGE. These radiolabelled species were absent in the presence of CGRP or amylin at 1 microM. These results are indicative of a common binding site for both CGRP and amylin in liver and skeletal muscle, and it is suggested that both peptides mediate their actions through the same effector system. The normal physiological importance and the relevance to the pathology of type 2 diabetes of these data are discussed.

Synthetic Human Calcitonin Gene Related Peptide in Action

2010 ◽  
Vol 16 (8) ◽  
pp. S73
Author(s):  
Asad Sheikh ◽  
James Vacek ◽  
Jeff Southard ◽  
Pamela Gayheart-Walsten ◽  
Ty Speece ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Human Calcitonin ◽  
Related Peptide ◽  
Calcitonin Gene

Effects of galanin and calcitonin gene-related peptide on insulin and glucagon secretion in man

1990 ◽  
Vol 123 (6) ◽  
pp. 591-597 ◽  
Author(s):  
Bo Ahrén
Keyword(s):  
Insulin Secretion ◽  
Plasma Insulin ◽  
Glucagon Secretion ◽  
Calcitonin Gene Related Peptide ◽  
Human Calcitonin ◽  
C Peptide ◽  
Related Peptide ◽  
Insulin And Glucagon Secretion ◽  
Calcitonin Gene ◽  
Human Volunteers

Abstract. To study the influence of the pancreatic neuropeptides, galanin and calcitonin gene-related peptide, on insulin and glucagon secretion in man, synthetic porcine galanin (80 pmol·kg−1·min−1; N=6) or synthetic human calcitonin gen-related peptide (10 pmol·kg−1·min−1; N = 5) was infused intravenously in human volunteers. Following 5 min of infusion, arginine (5 g bolus + 10 mg·kg−1·min−1) was given. Galanin did not affect basal or arginine-stimulated insulin secretion judged from determinations of plasma insulin and C-peptide. Similarly, galanin did not affect arginine-stimulated glucagon secretion. Calcitonin gene-related peptide did not affect basal or arginine-stimulated insulin or glucagon secretion. However, calcitonin gene-related peptide slightly potentiated the arginine-induced hyperglycemia (p<0.01). Thus, in man, galanin has no influence on insulin or glucagon secretion when infused at 80 pmol·kg−1·min−1, whereas CGRP at 10 pmol·kg−1·min−1 induces slight hyperglycemia.

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