5-HT2 receptor mRNA is overexpressed in cultured rat aortic smooth muscle cells relative to normal aorta

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Abstract
Proliferation of smooth muscle cells in arteries is associated with contractile hypersensitivity to serotonin (5-HT). A possible explanation is that smooth muscle cells express increased numbers of phospholipase C (PLC)-coupled 5-HT receptors (5-HTR), which could mediate contractile and mitogenic signals via phosphatidylinositol turnover. To test this hypothesis, we performed a molecular characterization of 5-HTR subtypes in normal aorta and passaged rat aortic smooth muscle cells (RASM) in culture. Northern blot analysis revealed that growth-arrested cultured cells expressed 5-HT2R mRNA at 50-fold greater levels than aorta. 5-HT1CR mRNA was not detected in either case. 5-HT stimulated intracellular Ca2+ mobilization (fivefold peak increase) and c-fos mRNA induction (10-fold peak increase); both responses were strongly inhibited by selective 5-HT2R antagonists. Specific agonists for the 5-HT1AR, 5-HT1BR, and 5-HT1DR failed to induce c-fos mRNA. Although 5-HT (10 microM) increased [3H]thymidine incorporation (28% relative to 10% calf serum), it was a weak mitogen for cultured RASM based on cell counts. Thus there is high level expression of 5-HT2R mRNA by cultured RASM relative to aorta, and the 5-HT2R appears to be the only 5-HTR subtype mediating early growth signals in these cells. These data suggest that, following arterial injury in vivo, smooth muscle cells may overexpress the 5-HT2R, resulting in 5-HT contractile hypersensitivity and increased responsiveness to other growth factors.