Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2000 Aug;130(8):1727-30.
doi: 10.1038/sj.bjp.0703500.

Adrenomedullin inhibits spontaneous and bradykinin-induced but not oxytocin- or prostaglandin F(2alpha)-induced periodic contraction of rat uterus

T Yanagita  1 , R Yamamoto, T Sugano, H Kobayashi, Y Uezono, H Yokoo, S Shiraishi, S I Minami, A Wada
Affiliations

Adrenomedullin inhibits spontaneous and bradykinin-induced but not oxytocin- or prostaglandin F(2alpha)-induced periodic contraction of rat uterus

T Yanagita et al. Br J Pharmacol. 2000 Aug.

Abstract

In isolated rat uterine strips, adrenomedullin (AM) inhibited the spontaneous periodic contraction in a concentration-dependent manner (IC(50)=22.3+/-0.7 nM). The inhibitory effect of AM was prevented by either AM(22-52), a putative antagonist for AM receptors, or calcitonin gene-related peptide (CGRP)(8-37), a putative antagonist for CGRP receptors. AM also attenuated bradykinin (BK)-induced periodic uterine contraction, which was blocked by AM(22-52) or CGRP(8-37), whereas AM had no effect on the periodic contraction caused by oxytocin or prostaglandin F(2alpha) (PGF(2alpha)). RT-PCR analysis showed that mRNAs for calcitonin receptor-like receptor (CRLR), receptor-activity-modifying protein (RAMP)1, RAMP2 and RAMP3 were expressed in the rat uterus. These results demonstrate that AM selectively inhibits spontaneous and BK-induced periodic contraction via activating receptors for AM and CGRP.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Effects of AM on spontaneous periodic contraction. Uterine strips of oestrogenized rats were treated with (a) vehicle; (b,c) AM; (d) AM22–52+AM; (e) CGRP8–37+AM. Typical recordings from five separate experiments with similar results were shown. (f) effect of AM22–52 or CGRP8–37 on the AM-induced inhibition of the contraction. *P<0.05, compared with the response without any peptide (one-way ANOVA); #P<0.05, compared with AM alone (two-way ANOVA).
Figure 2
Figure 2
Effects of AM on periodic contraction caused by oxytocin, PGF2α or BK. Uterine strips of non-oestrogenized rats were pretreated with (a) oxytocin; (b) PGF2α; (c–e) BK and further treated with (a–c) AM; (d) AM22–52+AM; (e) CGRP8–37+AM. Typical recordings from five separate experiments with similar results were shown.
Figure 3
Figure 3
Expression of mRNA for CRLR, RAMPs in rat uterus. RT–PCR products of CRLR and RAMPs were separated by agarose gel electrophoresis. The DNA size marker was 100 bp ladder as shown on the left. The predicted sizes of RT–PCR products are shown at the bottom.
See this image and copyright information in PMC

References

    1. BEK T., OTTESEN B., FAHRENKRUG J. The effect of galanin, CGRP and ANP on spontaneous smooth muscle activity of rat uterus. Peptides. 1988;9:497–500. - PubMed
    1. CAMERON V.A., FLEMING A.M. Novel sites of adrenomedullin gene expression in mouse and rat tissues. Endocrinology. 1998;139:2253–2264. - PubMed
    1. CHAMPION H.C., SANTIAGO J.A., MURPHY W.A., COY D.H., KADOWITZ P.J. Adrenomedullin-(22-52) antagonizes vasodilator responses to CGRP but not adrenomedullin in the cat. Am. J. Physiol. 1997;272:R234–R242. - PubMed
    1. CHIBA T., YAMAGUCHI A., YAMATANI T., NAKAMURA A., MORISHITA T., INUI T., FUKASE M., NODA T., FUJITA T. Calcitonin gene-related peptide receptor antagonist human CGRP-(8-37) Am. J. Physiol. 1989;256:E331–E335. - PubMed
    1. DE LA CADENA R.A., LASKIN K.J., PIXLEY R.A., SARTOR R.B., SCHWAB J.H., BACK N., BEDI G.S., FISHER R.S., COLMAN R.W. Role of kallikrein-kinin system in pathogenesis of bacterial cell wall-induced inflammation. Am. J. Physiol. 1991;260:G213–G219. - PubMed

Publication types

MeSH terms

Substances