This Research Program addresses the cellular/molecular mechanisms that cause stress- and obstruction-induced lower urinary tract symptoms (LUTS). A novel signaling lipid, lysophosphatidic acid (LPA) has been produced in numerous cell types and has been shown to greatly stimulate such processes as proliferation, dedifferentiation, and smooth muscle contraction. The effects of LPA on smooth muscle contraction appear to require Rho kinase activation and our laboratory has recently found that Rho kinase activity is elevated in rabbit bladder smooth muscle after partial bladder outlet obstruction (PBOO). The smooth muscle hypertrophy that occurs in PBOO is dependent on alterations in the lipid-dependent second messenger LPA.
The Specific Aim of Dr. Edward F. LaBelle's project is to determine the content of LPA in the smooth muscle cells of rabbit bladders exposed to PBOO. We will also determine the effects of contractile agonists (such as carbachol) on LPA content and release in bladder smooth muscle. The support through this Administrative Supplement will expand our objectives approved by the last competitive review and enable us to recruit more personnel to work in our program. In addition to the gain in scientific knowledge, this project would help Christopher J. Hypolite, a junior at Shippensburg University receiving hands-on experience in laboratory procedures.