Involvement of calcitonin gene-related peptide in control of human fetoplacental vascular tone.
Calcitonin gene-related peptide (CGRP), one of the most potent endogenous vasodilators known, has been implicated in vascular adaptations and placental functions during pregnancy. The present study was designed to examine the existence of CGRP-A receptor components, the calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1), in the human placenta and the vasoactivity of CGRP in the fetoplacental circulation. Immunofluorescent staining of the human placenta in term labor using polyclonal anti-CRLR and RAMP1 antibodies revealed that labeling specifically concentrated in the vascular endothelium and the underlying smooth muscle cells in the umbilical artery/vein, chorionic artery/vein, and stem villous vessels as well as in the trophoblast layer of the placental villi. In vitro isometric force measurement showed that CGRP dose dependently relaxes the umbilical artery/vein, chorionic artery/vein, and stem villous vessels. Furthermore, CGRP-induced relaxation of placental vessels are inhibited by a CGRP receptor antagonist (CGRP8-37), ATP-sensitive potassium (KATP) channel blocker (glybenclamide), and cAMP-dependent protein kinase A inhibitor (Rp-cAMPS) and partially inhibited by a nitric oxide inhibitor (Nomega-nitro-l-arginine methyl ester). We propose that CGRP may play a role in the control of human fetoplacental vascular tone, and the vascular dilations in response to CGRP may involve activation of KATP channels, cAMP, and a nitric oxide pathway.
Dong
Yuan-Lin
YL
Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 Univ. Blvd., Medical Research Bldg., Rm. 11.138, Galveston, TX 77555-1062, USA. ydong@utmb.edu
Vegiraju
Sujatha
S
Chauhan
Madhu
M
Gangula
Pandu R R
PR
Hankins
Gary D V
GD
Goodrum
Linda
L
Yallampalli
Chandra
C
D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D058286:Calcitonin Receptor-Like Protein; D005260:Female; D005333:Fetus / Q000098:blood supply* / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000098:blood supply* / Q000166:cytology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D058262:Receptor Activity-Modifying Protein 1; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014018:Tissue Distribution; D014664:Vasodilation / Q000502:physiology; D014666:Vasomotor System / Q000502:physiology*
C545578:CALCRL protein, human; D058286:Calcitonin Receptor-Like Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C545502:RAMP1 protein, human; D012333:RNA, Messenger; D058262:Receptor Activity-Modifying Protein 1; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin; D015740:Calcitonin Gene-Related Peptide