Stretch-induced morphological changes of human endothelial cells depend on the intracellular level of Ca 2+ rather than of cAMP

• Published in: Life sciences (1973) Vol. 67; no. 21; pp. 2605 - 2613
• Main Authors: Yamada, Takako, Naruse, Keiji, Sokabe, Masahiro
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 2000
• Subjects: DDA; Forskolin; Stretch-activated channel; Uni-axial cyclic stretch; DDA; Stretch-activated channel; Uni-axial cyclic stretch; Forskolin
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(00)00844-4

When exposed to a uni-axial cyclic stretch, cultured human umbilical vein endothelial cells (HUVECs) align and elongate perpendicular to the stretch axis. Previous studies showed that forskolin inhibited stretch-induced orientation of endothelial cells, suggesting that adenosine3:5-cyclic monophosphate (cAMP) plays an important role in the shape change. However, we have recently shown that stretch-induced shape changes in cultured HUVECs are due to increased [Ca 2+] i. In the present study, we examined the possible role of cAMP in stretch-induced shape changes in cultured HUVECs. Application of uni-axial cyclic stretch induced a gradual rise in cAMP reaching a peak level at 60 min after the onset of stretch. The adenylate cyclase activator, forskolin, increased the basal level of cAMP but inhibited the rise in [Ca 2+] i resulting in no cell shape changes. In contrast, N 6,2-dibutyryladenosine3:5-cyclic monophosphate (dbcAMP) enhanced the stretch-induced increase in cAMP and [Ca 2+] i and resulted in cell shape changes. On the other hand, 2′5′-dideoxyadenosine (DDA), an adenylate cyclase inhibitor, inhibited stretch-induced increases in cAMP and [Ca 2+] i resulting in no cell shape changes. In summary, our data showed that cell shape changes were consistently dependent on [Ca 2+] i rather than cAMP levels. We conclude that the primary second messenger in the stretch-induced shape changes in HUVECs is intracellular Ca 2+ rather than cAMP.