Inhibitory effect of calcitonin gene-related peptide on myometrial contractility is diminished at parturition.
The uterus is innervated by calcitonin gene-related peptide (CGRP) immunoreactive neurons, and CGRP inhibits spontaneous and evoked contractions in the uterus and fallopian tubes. In the present study using isometric force measurements on myometrial strips, we determined that CGRP inhibition of acetylcholine-induced contractions was drastically reduced at parturition compared with earlier stages of pregnancy in mice. The levels of inhibition exerted by CGRP paralleled the expression of a novel protein recently implicated in CGRP receptor activation, the CGRP-receptor component protein (CGRP-RCP). The mouse CGRP-RCP complementary DNA was isolated from uterus, and expression of the CGRP-RCP was monitored during gestation by Northern and Western blot analysis. Although CGRP-RCP messenger RNA levels did not vary significantly during gestation and postpartum, CGRP-RCP protein was greatly diminished at parturition. This diminution correlated with the loss of CGRP inhibition of acetylcholine-induced contractions observed in the force experiments. A role for CGRP and CGRP-RCP in modulation of myometrial smooth muscle contractility during pregnancy and in labor is suggested.
Naghashpour
M
M
Department of Physiology and Biophysics, University of Miami School of Medicine, Florida 33136, USA.
Rosenblatt
M I
MI
Dickerson
I M
IM
Dahl
G P
GP
D000109:Acetylcholine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D018076:DNA, Complementary / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D004347:Drug Interactions; D005260:Female; D005786:Gene Expression Regulation; D006168:Guinea Pigs; D007743:Labor, Obstetric / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009215:Myometrium / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D009865:Oocytes / Q000737:chemistry / Q000166:cytology; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000032:analysis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology
C491563:Crcp protein, mouse; D018076:DNA, Complementary; D012333:RNA, Messenger; D018015:Receptors, Calcitonin Gene-Related Peptide; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine