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Closed Access item Functional characterisation of hemokinin-1 in mouse uterus

Authors:Patak, Eva
Pennefather, Jocelyn N.
Gozali, Marshella
Candenas de Luján, M. Luz
Kerr, Karen
Exintaris, Betty
Ziccone, Sebastian
Potteck, Henrik
Chetty, Navinisha
Page, Nigel M.
Pinto Pérez, Francisco M.
Keywords:Hemokinin, Oestrogen, Pregnancy, Tachykinin, NK1 and NK2 receptor
Issue Date:26-Oct-2008
Citation:European Journal of Pharmacology 601(1-3): 148-153 (2008)
Abstract:The preprotachykinin gene Tac4 expressed in murine uterus and placenta is thought to encode a peptide RSRTRQFYGLM-NH2, mouse hemokinin 1. We have examined the uterotonic effects of mouse hemokinin 1 and its N-terminally truncated analogue, mouse hemokinin 1(2–11) on mouse uterus. Mouse hemokinin 1(2–11) was equieffective with but slightly less potent than substance P in tissues from non-pregnant Swiss mice. On myometrium from Balb C mice primed with oestrogen the positions of concentration–response curves to substance P and the mouse hemokinins were similar to those of neurokinin A, but the maximum responses were lower. The tachykinin NK1 receptor antagonist, 1-{2-(3, 4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl) piperidin-3-yl]ethyl}-4phenyl-1-azonia-bicyclo[2.2.2]octane (SR 140333), reduced the effects of the agonists in tissues from both groups of mice. In myometria from late pregnant (Days 17–18) Balb C mice the responses to mouse hemokinin 1(2–11) were less potent than in those from oestrogen-primed mice. Human hemokinin 1, the human orthologue of mouse hemokinin 1, was more effective than mouse hemokinin 1(2–11), while endokinin D was inactive. Mouse hemokinin 1 effects were blocked by SR 140333 alone and in combination with ((S)-N-methyl-N[4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butyl]benzamide (SR 48968) but not by SR 48968 alone. Thus the mouse hemokinins are tachykinin NK1 receptor-preferring uterotonic agonists in non-pregnant mice but lack action at the myometrial tachykinin NK2 receptors present in late pregnant mice.
Description:6 páginas, 4 figuras, 1 tabla.
Publisher version (URL):http://dx.doi.org/10.1016/j.ejphar.2008.10.036
Appears in Collections:(IIQ) Artículos

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