What question did this study set out to answer?

To determine the role of endothelin-1 receptor internalization and recycling in sustaining contractile responses in vascular smooth muscle.

Receptor externalization determines sustained contractile responses to endothelin-1 in the rat aorta

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To determine the role of endothelin-1 receptor internalization and recycling in sustaining contractile responses in vascular smooth muscle.
Measured 125I-labeled endothelin-1 (125I-ET-1) binding, internalization, and cell-surface reappearance in cultured rat aortic myocytes in the presence or absence of cycloheximide.
Evaluated functional vasoconstrictor responses and receptor inhibition using the ETA receptor antagonist BQ-123 in isolated rat aortic strips.
Binding of 125I-ET-1 triggered rapid receptor internalization followed by slow reappearance of functional receptors at the cell surface through a cycloheximide-insensitive recycling pathway.
The selective ETA antagonist BQ-123 prevented 125I-ET-1 binding with a dissociation constant of 10 nM and selectively inhibited ET-1-induced vasoconstriction without affecting angiotensin II.
BQ-123 completely relaxed ET-1-precontracted aortic strips regardless of when it was added, demonstrating ongoing receptor recruitment is required to maintain contraction.

Population

Cultured rat aortic myocytes and rat aortic strips

Intervention

Endothelin-1 (ET-1) and ETA receptor antagonist BQ-123

Outcome

Receptor internalization, recycling, and contractile responsesurrogate

Recycling of internalized ET-1 receptors in aortic myocytes amplifies the action of endothelin-1, explaining its unique sustained contractile effect.

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ETA antagonism interrupts sustained ET-1 contraction in rat aorta; leaves open clinical relevance in human vascular disease.

Marsault et al. (1993) studied this question.

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