Distinct hemodynamic and renal effects of calcitonin gene-related peptide and calcitonin in men

1989 ◽  
Vol 257 (6) ◽  
pp. E848-E854 ◽  
Author(s):  
M. P. Gnaedinger ◽  
D. E. Uehlinger ◽  
P. Weidmann ◽  
S. G. Sha ◽  
R. Muff ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Cardiovascular Effects ◽  
Fractional Excretion ◽  
Calcitonin Gene Related Peptide ◽  
Human Calcitonin ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Excretion Rates ◽  
Normal Men

Cardiovascular and renal actions of human calcitonin gene-related peptide II (or beta) (CGRP) and of human calcitonin (CT) infused intravenously for 1 h each (79 and 263 pmol.kg-1.h-1) have been compared in normal men (n = 10 for CGRP, n = 6 for CT and vehicle alone). CGRP lowered diastolic blood pressure by 26% and increased the heart rate by 35% and raised plasma levels of norepinephrine, epinephrine, and dopamine and renin activity (P less than 0.01). The fractional excretion rates (FE) of sodium and chloride were doubled (P less than 0.05-0.01) in the presence of an unaltered glomerular filtration rate. CT, on the other hand, did not affect the diastolic blood pressure, but the stimulation of diuresis and of the FE of sodium and chloride was more pronounced with CT than with CGRP (P less than 0.01). Moreover, CT lowered serum calcium levels and stimulated urinary adenosine 3',5'-cyclic monophosphate and phosphate excretion (P less than 0.01). In conclusion, the cardiovascular effects of CGRP are contrasted by weaker renal tubular actions of the neuropeptide in relation to CT.

Haemodynamic effects of intravenous human calcitonin-gene-related peptide in man

1988 ◽  
Vol 74 (4) ◽  
pp. 413-418 ◽  
Author(s):  
C. W. Howden ◽  
Catherine Logue ◽  
Karen Gavin ◽  
Lizbeth Collie ◽  
P. C. Rubin
Keyword(s):  
Blood Pressure ◽  
Standing Position ◽  
Calcitonin Gene Related Peptide ◽  
Double Blind Study ◽  
Human Calcitonin ◽  
Facial Flushing ◽  
Double Blind ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Higher Doses

1. The effects of intravenous bolus doses of human calcitonin-gene-related peptide (hCGRP) were studied in ten healthy male volunteers. 2.5, 10 and 25 μg of hCGRP and placebo were administered to each subject in a randomized double-blind study. 2. hCGRP had no effect on systolic or diastolic blood pressure in the supine or standing position. 3. hCGRP increased supine and standing heart rate. Both the extent and duration of the tachycardia were dose related. 4. Plasma noradrenaline levels were transiently increased after 10 and 25 μg of hCGRP. 5. All subjects displayed marked facial flushing after the two higher doses of hCGRP. 6. We conclude that systemic administration of hCGRP produces tachycardia and stimulation of the sympathetic nervous system in the absence of any change in blood pressure.

The cardiovascular effects of human calcitonin gene-related peptide in conscious sheep

1988 ◽  
Vol 6 (11) ◽  
pp. 881-887 ◽  
Author(s):  
Karl G. Braslis ◽  
David R. Fletcher ◽  
Arthur Shulkes ◽  
Bruce A. Scoggins ◽  
Janette Tresham ◽  
...  
Keyword(s):  
Cardiovascular Effects ◽  
Calcitonin Gene Related Peptide ◽  
Human Calcitonin ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Conscious Sheep

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 Rimegepant: first novel oral calcitonin gene-related peptide inhibitor for migraine

2020 ◽  
Vol 9 (5) ◽  
pp. 829
Author(s):  
Saravana Kumar Ramasubbu ◽  
Senkadhirdasan Dakshinamurthy ◽  
Sarika Palepu ◽  
Arkapal Bandyopadhyay ◽  
Sathish Kumar Rajendran
Keyword(s):  
Area Under The Curve ◽  
Cardiovascular Effects ◽  
Calcitonin Gene Related Peptide ◽  
Causative Role ◽  
Acute Migraine ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Effective Option ◽  
Inflammatory Drugs ◽  
Cgrp Antagonist

Migraine is a neurological condition characterized by intense, debilitating headaches. Symptoms may include nausea, vomiting, numbness or tingling, sensitivity to light and sound. There are multitude of drugs available to treat migraine like triptans, non-steroidal anti-inflammatory drugs, ergots and opioids. But these drugs are associated with adverse effects especially triptans causing cardiovascular effects limiting its use. During last decade, calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for management of migraine. CGRP has been shown to release during episode of migraine attack and it may play a causative role in induction of migraine. Rimegepant is a novel CGRP antagonist has been approved by FDA for treatment of acute migraine. Rimegepant is a first oral CGRP antagonist compared to other gepants. The oral bioavailability of Rimegepant is 64% and high fat meal can decrease the Cmax, Tmax and area under the curve. This drug is mainly metabolized by CYP3A4 and to lesser extent by CYP2C9. Most common adverse reactions associated with this drug were nausea and urinary tract infection. Clinical trials for Rimegepant have been positive, and results suggest that the drug may be a new safe and effective option for treatment of acute migraine.

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
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