Calcitonin gene-related peptide in pregnancy and its emerging receptor heterogeneity

Calcitonin gene-related peptide(CGRP) is the most potent vasodilator, and there is a growing body of evidence that this peptide might have multiple other functions. During pregnancy, circulating CGRP levels in rats increase up to the time of delivery, followed by a sharp decline at term and postpartum. In addition, the sensitivity of various vascular beds to CGRP in rats appears to increase with advancing pregnancy. This increased sensitivity might be involved in regulating uteroplacental blood flow, in addition to other vascular adaptations that occur during normal pregnancy. Furthermore, the uterine relaxation response to CGRP is elevated during pregnancy and decreased at term. Sex steroid hormones, estrogens and progesterone, regulate CGRP synthesis and its effects on both myometrial and uterine vascular tissues. These changes in smooth muscle relaxation sensitivity to CGRP appear to be a consequence of changes in CGRP-receptor levels in these tissues. There appear to be two receptors for CGRP: the CGRP-A receptor, a well-characterized receptor consisting of calcitonin receptor-like receptor and receptor activity modifying protein 1, and the CGRP-B receptor. The CGRP system might play a role in the maintenance of normal pregnancy, and a defect in this system might lead to complications.