What question did this study set out to answer?

To elucidate the signaling pathways and functional interplay between endothelin-1 and nitric oxide in regulating calcium mobilization and cytoskeletal remodeling in human brain capillary endothelial cells.

February 1, 2003AJP Cell Physiology

ET-1- and NO-mediated signal transduction pathway in human brain capillary endothelial cells

View Full Paper

Ask AI

Bookmark

To elucidate the signaling pathways and functional interplay between endothelin-1 and nitric oxide in regulating calcium mobilization and cytoskeletal remodeling in human brain capillary endothelial cells.
Measured calcium mobilization in cultured human brain capillary endothelial cells treated with endothelin-1, the nitric oxide donor NOR-1, and 8-bromo-cGMP.
Applied pharmacological inhibitors of soluble guanylyl cyclase (ODQ) and protein kinase G (Rp-8-CPT-cGMPS), alongside G-protein, IP3, and Ca2+-ATPase modulators.
Evaluated endothelial cytoskeletal remodeling (actin and vimentin), protein kinase G localization, and vasodilator-stimulated phosphoprotein (VASP) phosphorylation.
NOR-1 dose-dependently inhibited ET-1-induced Ca2+ mobilization, an effect reversed by guanylyl cyclase inhibitor ODQ and protein kinase G inhibitor Rp-8-CPT-cGMPS.
NOR-1 and cGMP suppressed Ca2+ mobilization triggered by mastoparan, inositol 1,4,5-trisphosphate, and thapsigargin, correlating with actin and vimentin cytoskeletal alterations.
Protein kinase G colocalized with actin, and NOR-1 elevated phosphorylated VASP levels, which were significantly attenuated by ODQ or Rp-8-CPT-cGMPS.

Structured PICO

Population

Human brain capillary endothelial cells

Intervention

Endothelin-1 (ET-1) and NOR-1 (NO donor), along with various inhibitors and activators (ODQ, Rp-8-CPT-cGMPS, 8-bromo-cGMP, mastoparan, inositol 1,4,5-trisphosphate, thapsigargin)

Outcome

Ca(2+) mobilization and cytoskeleton alterations (actin and vimentin)surrogate

The functional interplay between ET-1 and NO in human brain capillary endothelial cells involves cGMP-dependent protein kinase regulation of calcium mobilization and cytoskeletal dynamics, potentially regulating capillary tone and blood-brain barrier function.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Hypothesis-generating for ET-1/NO interplay in cerebral capillaries; leaves in vivo relevance and clinical translation open.

Cite This Study

Chen et al. (2003) studied this question.

synapsesocial.com/papers/6a708bf122b3175134db53bb https://doi.org/10.1152/ajpcell.00305.2002

View Full Paper

Ask AI

Bookmark

ET-1- and NO-mediated signal transduction pathway in human brain capillary endothelial cells

Key Points

Structured PICO

Discussion

Implication

Cite This Study

ET-1- and NO-mediated signal transduction pathway in human brain capillary endothelial cells

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Also Consider