Female Sex Steroid Hormones and Pregnancy Regulate Receptors for Calcitonin Gene-Related Peptide in Rat Mesenteric Arteries, but Not in Aorta

• Published in: Biology of reproduction 2004-04, Vol.70 (4), p.1055-1062
• Main Authors: YALLAMPALLI, C, KONDAPAKA, S. B, LANLUA, P, WIMALAWANSA, S. J, GANGULA, P. R. R
• Format: Article
• Language: English
• Subjects: Animals; Aorta - drug effects; Aorta - metabolism; Biological and medical sciences; Calcitonin Gene-Related Peptide - metabolism; Calcitonin Receptor-Like Protein; Down-Regulation; Drug Combinations; Estradiol - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Hormone Antagonists - pharmacology; Hormone metabolism and regulation; Intracellular Signaling Peptides and Proteins; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mesenteric Arteries - drug effects; Mesenteric Arteries - metabolism; Mifepristone - pharmacology; Osmolar Concentration; Ovariectomy; Pregnancy - metabolism; Pregnancy. Parturition. Lactation; Progesterone - pharmacology; Protein Isoforms - metabolism; Rats; Rats, Sprague-Dawley; Receptor Activity-Modifying Protein 1; Receptor Activity-Modifying Proteins; Receptors, Calcitonin - genetics; Receptors, Calcitonin - metabolism; Receptors, Calcitonin Gene-Related Peptide - metabolism; RNA, Messenger - metabolism; Up-Regulation; Vertebrates: reproduction
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.103.022467

Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide known to be involved in the regulation of vascular tone. Results of previous studies from our laboratory and others suggest that vascular sensitivity to CGRP is enhanced during pregnancy and that the female sex steroid hormones estradiol-17β (E 2 ) and progesterone (P 4 ) may be involved in this process. We hypothesized that CGRP receptors in the mesenteric artery are increased during pregnancy and with sex steroid hormone treatments. In the present study, we investigated whether pregnancy and female sex steroid hormones modulate the CGRP-receptors CGRP-A and CGRP-B in the mesenteric artery in the rat. The CGRP-A receptor consists of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP 1 ); however, the CGRP-B receptor needs to be further characterized. Messenger RNA levels for CRLR and RAMP 1 were assessed by reverse transcription-polymerase chain reaction, and CGRP-B receptor proteins levels were determined by Western blot analysis. In addition, [ 125 I]CGRP binding was measured by Scatchard analysis. Both mRNA for CGRP-A (CRLR and RAMP 1 ) and the protein for CGRP-B receptors in mesenteric arteries were increased with pregnancy compared to nonpregnant, diestrous animals. A P 4 antagonist, RU-486, downregulated and P 4 upregulated these receptors in mesenteric arteries ( P < 0.05) in pregnant rats. In adult ovariectomized rats, P 4 upregulated CRLR and RAMP 1 mRNA levels as well as [ 125 I]CGRP-binding sites. The CGRP-B-receptor protein levels were significantly ( P < 0.05) elevated by P 4 and by combined E 2 and P 4 treatment. Together with earlier findings, these data suggest that increases in the expression of CGRP-A (CRLR and RAMP 1 ) and CGRP-B receptors in mesenteric arteries may be important in reducing vascular resistance and in vascular adaptations that occur during pregnancy; in addition, P 4 may be involved in this process.