Rationale: Calcitonin gene-related peptide (CGRP) and its family members adrenomedullin (ADM) and adrenomedullin 2 (ADM2; also known as intermedin) support vascular adaptions in rat pregnancy.
Objective: This study aimed to assess the relaxation response of uterine artery (UA) for CGRP, ADM, and ADM2 in nonpregnant and pregnant women and identify the involved mechanisms.
Findings: (1) Segments of UA from nonpregnant women that were precontracted with U46619 (1μM) in vitro are insensitive to the hypotensive effects of CGRP, ADM, and ADM2; (2) CGRP, ADM, and ADM2 (0.1-100nM) 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 comprising 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 RAMP1 mRNA (P < 0.05) in UASMC; and (7) sFLT-1 treatment impairs the association of CRLR with all 3 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; vascular disruptors such as sFLT-1 and TNFα adversely impact their receptor system in UASMC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8574633 | PMC |
| http://dx.doi.org/10.1210/endocr/bqab204 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sex differences in expression of CGRP family of receptors and ligands in the rat trigeminal system.
J Headache Pain
November 2024
Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden.
Article Synopsis
- Calcitonin gene-related peptide (CGRP) is a significant member of the calcitonin family and is concentrated in the trigeminovascular system (TVS), which is relevant for migraine treatment.
- The study involved dissection of trigeminal ganglia from male and female rats, assessing the expression of various peptides and their receptors using techniques like immunohistochemistry and RT-qPCR.
- Results indicated a higher expression of CGRP mRNA in both genders, a notable increase of receptor activity-modifying protein-1 (RAMP1) in females, and the presence of varying peptides and receptors localized in the TG neurons, emphasizing CGRP's crucial role in the TVS.
Oocyte-specific disruption of adrenomedullin 2 gene enhances ovarian follicle growth after superovulation.
Front Endocrinol (Lausanne)
December 2022
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University, Taoyuan, Taiwan.
Background: Adrenomedullin 2 (ADM2), adrenomedullin (ADM), and calcitonin gene-related peptides (α- and β-CGRPs) signal through heterodimeric calcitonin receptor-like receptor/receptor activity-modifying protein 1, 2 and 3 (CLR/RAMP1, 2 and 3) complexes. These peptides are important regulators of neurotransmission, vasotone, cardiovascular development, and metabolic homeostasis. In rodents, ADM is essential for regulating embryo implantation, fetal-placental development, and hemodynamic adaptation during pregnancy.
View Article and Find Full Text PDFModulation of Glia Activation by TRPA1 Antagonism in Preclinical Models of Migraine.
Int J Mol Sci
November 2022
Department of Brain and Behavioral Sciences, University of Pavia, Via Bassi 21, 27100 Pavia, Italy.
Preclinical data point to the contribution of transient receptor potential ankyrin 1 (TRPA1) channels to the complex mechanisms underlying migraine pain. TRPA1 channels are expressed in primary sensory neurons, as well as in glial cells, and they can be activated/sensitized by inflammatory mediators. The aim of this study was to investigate the relationship between TRPA1 channels and glial activation in the modulation of trigeminal hyperalgesia in preclinical models of migraine based on acute and chronic nitroglycerin challenges.
View Article and Find Full Text PDFSustained Activation of CLR/RAMP Receptors by Gel-Forming Agonists.
Int J Mol Sci
November 2022
Adepthera LLC, San Jose, CA 95138, USA.
Background: Adrenomedullin (ADM), adrenomedullin 2 (ADM2), and CGRP family peptides are important regulators of vascular vasotone and integrity, neurotransmission, and fetoplacental development. These peptides signal through CLR/RAMP1, 2, and 3 receptors, and protect against endothelial dysfunction in disease models. As such, CLR/RAMP receptor agonists are considered important therapeutic candidates for various diseases.
View Article and Find Full Text PDFHuman amniotic fluid stem cell therapy can help regain bladder function in type 2 diabetic rats.
World J Stem Cells
May 2022
Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Background: Diabetes mellitus (DM) is a serious and growing global health burden. It is estimated that 80% of diabetic patients have micturition problems such as poor emptying, urinary incontinence, urgency, and urgency incontinence. Patients with diabetic bladder dysfunction are often resistant to currently available therapies.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!