Characterization of EDG receptor expression and proliferative response in cultured human BPH smooth muscle cells

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Adolfsson, Per I.Linköpings universitet,Farmakologi,Hälsouniversitetet (author)

Characterization of EDG receptor expression and proliferative response in cultured human BPH smooth muscle cells

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LIBRIS-ID:oai:DiVA.org:liu-80084
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-80084URI

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Language:English
Summary in:English

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The endogenous phospholipids, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both known to generate a Vvide variety of effects in various cell systems by the endothelial differentiation gene (Edg) receptor family, including 7 different G-protein coupled Edg receptors.In this study, expression of LPA- and SlP Edg receptors was examined, and so was the effect with respect to proliferation on cultured BPH smooth muscle cells smc. Mmeover, theresponse on cAMP levels was examined. Finally, a potential link between activation of the MAP kinase cascade and the LPA stimulated proliferation was investigated.First, the RT-PCR analysis of the Edg receptors in BPH smc, demonstrated a heterogeneous expression including all receptors except the Edg6 subtype. Further, in contrast to LPA, the mitogen effect of SIP, demonstrated a concentration-dependent biphasic response, including stimulation below 1μM, whereas inhibition was obtained at higher concentrations. Forskolin induced a rapid and transient cAMP response in LPA stimulated cells, with a peak-value after 3 minutes. After 15 minutes the cAMP level had retmned to base-line level. However a gradual increase to 15% of maximum value was obtained after additional 30 minutes, and thereafter a gradual reduction was observed. The mentioned antiproliferative response generated by SIP could not be conelated to an intracellular cAMP increase. Finally, when the LPA treated smc was co-incubated with the MAPK kinase inhibitor PD98059 (10 μM) the mitogen response was eliminated.The cAIVIP increase, which was induced by forskolin, corresponds with mentioned antiproliferative effect whereas a similar con-elation was not obtained regarding SIP. The intracellular signal mechanisms triggered by LPA and S1P in BPH smc remain to be further investigated.

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MEDICINE
MEDICIN

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Ahlstrand, ChristerLinköpings universitet,Urologi,Hälsouniversitetet(Swepub:liu)chrah61 (author)
Varenhorst, EberhardLinköpings universitet,Urologi,Hälsouniversitetet(Swepub:liu)ebeva05 (author)
Hultgren, SittiLinköpings universitet,Farmakologi,Hälsouniversitetet (author)
Svensson, Samuel P. S.Linköpings universitet,Farmakologi,Hälsouniversitetet(Swepub:liu)samsv36 (author)
Linköpings universitetFarmakologi (creator_code:org_t)

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