Functional characterisation of hemokinin-1 in mouse uterus

• Published in: European journal of pharmacology Vol. 601; no. 1; pp. 148 - 153
• Main Authors: Patak, Eva, Pennefather, Jocelyn N., Gozali, Marshella, Candenas, Luz, Kerr, Karen, Exintaris, Betty, Ziccone, Sebastian, Potteck, Henrik, Chetty, Navinisha, Page, Nigel M., Pinto, Francisco
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28.12.2008; Elsevier
• Subjects: Animals; Biological and medical sciences; Female; Hemokinin; Medical sciences; Mice; Mice, Inbred BALB C; Myometrium - metabolism; Neurokinin A - pharmacology; NK 1 and NK 2 receptor; Oestrogen; Pharmacology. Drug treatments; Pregnancy; Pregnancy, Animal; Protein Precursors - metabolism; Protein Precursors - pharmacology; Receptors, Neurokinin-1 - drug effects; Receptors, Neurokinin-1 - metabolism; Receptors, Neurokinin-2 - drug effects; Receptors, Neurokinin-2 - metabolism; Substance P - pharmacology; Tachykinin; Tachykinins - metabolism; Tachykinins - pharmacology; Uterus - metabolism; Pregnancy; Oestrogen; Hemokinin; NK 1 and NK 2 receptor; Tachykinin; NK1 Tachykinin receptor; Rodentia; Estrogen; Ovarian hormone; Vertebrata; Mammalia; Mouse; Uterus; NK1 and NK2 receptor; Animal; Female genital system; Female; NK2 Tachykinin receptor; Sex steroid hormone
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2008.10.036

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.