Functional characterisation of hemokinin-1 in mouse uterus.
The preprotachykinin gene Tac4 expressed in murine uterus and placenta is thought to encode a peptide RSRTRQFYGLM-NH(2), 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 NK(1) 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 NK(1) receptor-preferring uterotonic agonists in non-pregnant mice but lack action at the myometrial tachykinin NK(2) receptors present in late pregnant mice.
Patak
Eva
E
Department of Anaesthetics, Royal Women's Hospital, Parkville, Victoria 3052, Australia.
Pennefather
Jocelyn N
JN
Gozali
Marshella
M
Candenas
Luz
L
Kerr
Karen
K
Exintaris
Betty
B
Ziccone
Sebastian
S
Potteck
Henrik
H
Chetty
Navinisha
N
Page
Nigel M
NM
Pinto
Francisco
F
D000818:Animals; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009215:Myometrium / Q000378:metabolism; D015288:Neurokinin A / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal; D011498:Protein Precursors / Q000378:metabolism* / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000378:metabolism* / Q000494:pharmacology; D014599:Uterus / Q000378:metabolism*
D011498:Protein Precursors; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C423233:Tac4 protein, mouse; D015320:Tachykinins; C507968:hemokinin-1; D013373:Substance P; D015288:Neurokinin A