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Characterization of...
Characterization of EDG receptor expression and proliferative response in cultured human BPH smooth muscle cells
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- Adolfsson, Per I. (författare)
- Linköpings universitet,Farmakologi,Hälsouniversitetet
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- Ahlstrand, Christer (författare)
- Linköpings universitet,Urologi,Hälsouniversitetet
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- Varenhorst, Eberhard (författare)
- Linköpings universitet,Urologi,Hälsouniversitetet
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visa fler...
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- Hultgren, Sitti (författare)
- Linköpings universitet,Farmakologi,Hälsouniversitetet
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- Svensson, Samuel P. S. (författare)
- Linköpings universitet,Farmakologi,Hälsouniversitetet
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visa färre...
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- MEDICINE
- MEDICIN
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