Extracellular ATP mediated mechano-signaling in mammary glands

Accession number;04A0442620
Title;Extracellular ATP mediated mechano-signaling in mammary glands
Author; FURUYA KISHIO (Jst-icorp) AKITA KUMI (Jst-icorp) SOKABE MASAHIRO (Jst-icorp)
Journal Title;Folia Pharmacologica Japonica
Journal Code:G0740A
ISSN:0015-5691
VOL.123;NO.6;PAGE.397-402,412(2004)
Figure&Table&Reference;FIG.4, REF.31
Pub. Country;Japan
Language;Japanese
Abstract;ATP, an important and ubiquitous extracellular signaling molecule, is often released by mechanical stimuli and plays an essential role in mechano-signaling. In lactating mammary glands, secretory epithelial (SE) cells form alveoli in which milk is held, and myoepithelial (ME) cells surrounding the alveoli contract in response to oxytocin to expel milk. Previously we found that the contraction of ME cells worked as a mechanical stress to SE cells and caused ATP-release in cultured mammary epithelial cells. The released ATP activated P2Y2 in surrounding SE cells and P2Y1 in ME cells. We already reported that ATP synergistically enhanced oxytocin response in ME cells. These findings mean that ME and SE cells interact mutually via released ATP to enhance the milk ejection. Recently, we found that cell-stretch also induced Ca2+-increases and ATP-release. The stretching of alveoli should occur by milk filling. So, only the milk-filled alveoli (but not empty alveoli) are surrounded by ATP. The ATP lowers the threshold of the oxytocin receptors and enables the milk-filled alveoli to contract in response to oxytocin at a concentration in the blood. Slight but apparent constitutive-ATP-release was observed in non-stimulated cells and the release was enhanced in Ca2+-free solution. The pathway of ATP-release is not yet clear, but pharmacologically, there seems to be two or more pathways. (author abst.)