Calcitonin gene related peptide, adrenomedullin and adrenomedullin2 function in uterine artery during human pregnancy

Endocrinology ◽  
2021 ◽  
Author(s):  
Madhu Chauhan ◽  
Ancizar Betancourt ◽  
Meena Balakrishnan ◽  
Akansha Mishra ◽  
Jimmy Espinosa ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Uterine Artery ◽  
Calcitonin Gene Related Peptide ◽  
Calcitonin Receptor ◽  
Receptor System ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Tnf Α ◽  
Relaxation Responses

Abstract Rationale Calcitonin gene-related peptide (CGRP) and its family members adrenomedullin (ADM) and adrenomedullin2 (ADM2) also known as Intermedin support vascular adaptions in rat pregnancy. Objective To assess the relaxation response of uterine artery (UA) for CGRP, ADM, and ADM2 in non-pregnant and pregnant women and identify the involved mechanisms. Findings 1) Segments of UA from non-pregnant women that were pre-contracted with U46619 (1μM) in-vitro are insensitive to the hypotensive effects of CGRP, ADM and ADM2, 2) CGRP, ADM, and ADM2 (0.1nM – 100nM) dose-dependently relax UA segments from pregnant women with efficacy for CGRP>ADM=ADM2 , 3) The relaxation responses to CGRP, ADM and ADM2 are differentially affected by the inhibitors of nitric oxide (NO) synthase (L-NAME), adenylyl cyclase (SQ22536), apamin and charybdotoxin, 4) UA smooth muscle cells (UASMC) express mRNA for calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP)1 and RAMP2 but not RAMP3, 5) Receptor heterodimer comprised of CRLR/RAMP1 and CRLR/RAMP2 but not CRLR/RAMP3 is present in UA, 6) soluble fms-like tyrosine kinase (sFLT-1) and TNF-α treatment decrease the expression of RAMP1mRNA (p< 0.05) in UASMC and, 7) sFLT-1 treatment impairs the association of CRLR with all the three peptides while TNF-α inhibits the interaction of CGRP but not ADM or ADM2 with CRLR in UASMC (p< 0.05). Conclusions Relaxation sensitivity of UA for CGRP, ADM and ADM2 is increased during pregnancy via peptide specific involvement of NO system and endothelium derived hyperpolarizing factors, and vascular disruptors such as sFLT-1 and TNFα adversely impact their receptor system in UASMC.

Tapentadol inhibits calcitonin gene-related peptide release from rat brainstem in vitro

Peptides ◽  
2014 ◽  
Vol 56 ◽  
pp. 8-13 ◽  
Author(s):  
Maria Cristina Greco ◽  
Lucia Lisi ◽  
Diego Currò ◽  
Pierluigi Navarra ◽  
Giuseppe Tringali
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Peptide Release ◽  
Rat Brainstem

A New Calcitonin-Receptor-like Sequence in Rat Pulmonary Blood Vessels

1993 ◽  
Vol 85 (4) ◽  
pp. 385-388 ◽  
Author(s):  
F. Njuki ◽  
C. G. Nicholl ◽  
A. Howard ◽  
J. C. W. Mak ◽  
P. J. Barnes ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Vascular Tone ◽  
Islet Amyloid Polypeptide ◽  
Calcitonin Gene Related Peptide ◽  
Binding Activity ◽  
Calcitonin Receptor ◽  
Islet Amyloid ◽  
Related Peptide ◽  
Calcitonin Gene

1. Two rat clones have been isolated which are similar to known calcitonin-receptor sequences. One of these does not have the distribution expected of a calcitonin receptor. It is widely distributed, with extremely high levels of expression in the lung, where it is associated with the blood vessels. 2. This rat sequence may represent the receptor for calcitonin-gene-related peptide or islet amyloid polypeptide. Both have binding activity in the lung and are potent vasodilators. The gene represented by this sequence may therefore play an important role in the maintenance of vascular tone.

Calcitonin gene-related peptide is a survival factor, inhibiting apoptosis in neonatal rat gubernaculum in vitro

2009 ◽  
Vol 44 (8) ◽  
pp. 1497-1501 ◽  
Author(s):  
Jessica J. Chan ◽  
Pam J. Farmer ◽  
Bridget R. Southwell ◽  
Magdy Sourial ◽  
John M. Hutson
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Neonatal Rat ◽  
Related Peptide ◽  
Survival Factor ◽  
Calcitonin Gene

scholarly journals Renal microvascular actions of calcitonin gene-related peptide

1998 ◽  
Vol 274 (6) ◽  
pp. F1078-F1085 ◽  
Author(s):  
Martina Reslerova ◽  
Rodger Loutzenhiser
Keyword(s):  
Angiotensin Ii ◽  
Rat Kidney ◽  
Elevated Pressure ◽  
Calcitonin Gene Related Peptide ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Renal Vasoconstriction ◽  
Related Peptide ◽  
Calcitonin Gene

Calcitonin gene-related peptide (CGRP) is a potent vasodilator that is suggested to act via ATP-sensitive K channels (KATP). In the present study, we examined the actions of CGRP on pressure- and angiotensin II-induced vasoconstriction, using the in vitro perfused hydronephrotic rat kidney. Elevated pressure (from 80 to 180 mmHg) and 0.1 nM angiotensin II elicited similar decreases in afferent diameter in this model. CGRP inhibited myogenic reactivity in a concentration-dependent manner, completely preventing pressure-induced constriction at 10 nM (95 ± 10% inhibition). These effects were partially attenuated by 10 μM glibenclamide (62 ± 16% inhibition, P = 0.025), indicating both KATP-dependent and -independent actions of CGRP. In contrast, 10 nM CGRP inhibited angiotensin II-induced vasoconstriction by only 54 ± 11%, and this action was not affected by glibenclamide (41 ± 11%, P = 0.31). CGRP also inhibited the efferent arteriolar response to angiotensin II in the absence and presence of glibenclamide. Pinacidil (1.0 μM), a KATP opener also preferentially inhibited pressure- vs. angiotensin II-induced vasoconstriction (97 ± 5 and 59 ± 13% inhibition, respectively; P = 0.034). We conclude that the renal vasodilatory mechanisms of CGRP are pleiotropic and involve both KATP-dependent and -independent pathways. The effectiveness of CGRP in opposing renal vasoconstriction and the role of KATP in this action appear to depend on the nature the underlying vasoconstriction. We suggest that this phenomenon reflects an inhibition of KATP activation by angiotensin II.

Reversal of nerve damage in streptozotocin-diabetic rats by acute application of insulin in vitro

1988 ◽  
Vol 75 (6) ◽  
pp. 629-635 ◽  
Author(s):  
Geoffrey Burnstock ◽  
Rhona Mirsky ◽  
Abebech Belai
Keyword(s):  
Vasoactive Intestinal Polypeptide ◽  
Calcitonin Gene Related Peptide ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Rat Ileum ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Enteric Nerves ◽  
Intestinal Polypeptide

1. Immunohistochemical, immunoblotting and release experiments were performed on ileum from control rats, from 8-week streptozotocin-diabetic rats and from diabetic rats after acute application of insulin in vitro. 2. There was an increase in vasoactive-intestinal-polypeptide-like and a decrease in calcitonin-gene-related-peptide-like immunoreactivity in the myenteric plexus of the diabetic rat ileum, although electrically evoked release of both peptides from enteric nerves was defective. Acute application of insulin in vitro reversed the defective release and changes in immunoreactivity of vasoactive intestinal polypeptide and calcitonin-gene-related peptide seen in the enteric nerves of streptozotocin-diabetic rat ileum. 3. In addition, using a monoclonal neurofilament antibody RT 97 that recognizes a phosphorylated neurofilament epitope present in normal enteric nerves, it was shown that this phosphorylated neurofilament epitope was absent in diabetic nerves, even though a polyclonal neurofilament antibody revealed that neurofilaments were present in both axons and cell bodies of the myenteric plexus of diabetic rat ileum. After only 2 h of insulin incubation in vitro, the phosphorylated neurofilament epitope was again present in the nerves. 4. It is suggested that the abnormal distribution of phosphorylated neurofilaments and defective storage and release of vasoactive intestinal polypeptide and calcitonin-gene-related peptide in the present study may be a more general feature of diabetes. The restoration of these abnormalities by continuous acute insulin application in vitro shown here suggests that the availability of a steady level of insulin might prevent some of the changes which occur in early stages of diabetes. If so, this could influence the use of insulin in the treatment of diabetes, particularly in view of the recent report that short-term continuous subcutaneous insulin infusion restores the function of the autonomic and peripheral nerves in type I diabetic patients [Krönert, K., Hülsen, J., Luft, D., Stetter, T. & Eggstein, M. (1987) Journal of Clinical Endocrinology and Metabolism, 64, 1219–1223].

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