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(Circulation. 1996;93:2170-2177.)
© 1996 American Heart Association, Inc.

Articles

Serotonin Stimulates the Expression of Thrombin Receptors in Cultured Vascular Smooth Muscle Cells

Role of Protein Kinase C and Protein Tyrosine Kinases

Valérie B. Schini-Kerth, PhD; Beate Fisslthaler, PhD; Ellen Van Obberghen-Schilling, PhD; Rudi Busse, MD, PhD

From the Center of Physiology, University Clinic of Frankfurt (Germany), and the Centre de Biochimie, Université de Nice (France) (E.V.O.-S.).

Background Thrombin has been implicated in the development of intimal thickening after balloon angioplasty. The action of thrombin on vascular cells involves the proteolytic activation of G protein–coupled receptors that are subjected to rapid and irreversible homologous desensitization. Hence, the amount and availability of thrombin-activatable receptors play a determinant role in thrombin responsiveness. The possibility that the platelet-derived product serotonin (5-HT) regulates expression of the thrombin receptor was examined in cultured rat aortic vascular smooth muscle cells.

Methods and Results Thrombin receptor expression was assessed at the mRNA level by Northern blot analysis and functionally by measurement of the release of 6-ketoprostaglandin F₁. 5-HT significantly enhanced thrombin receptor mRNA levels in a time- and concentration-dependent manner, an effect that was abolished by 5-HT₂ receptor antagonists and by inhibition of protein kinase C but only slightly affected by inhibitors of protein tyrosine kinases. Enhanced thrombin receptor mRNA levels after exposure to 5-HT were associated with an increase in the thrombin-induced release of 6-ketoprostaglandin F₁.

Conclusions 5-HT stimulates the expression of thrombin receptors in vascular smooth muscle cells, probably via activation of 5-HT₂ receptors and the subsequent activation of protein kinase C and possibly also protein tyrosine kinases. The upregulation of the synthesis of plasma membrane thrombin receptors by 5-HT released from aggregating platelets at sites of vascular injury may potentiate the mitogenic and constrictor actions of thrombin in the vascular wall.

Key Words: serotonin • arteriosclerosis • muscle, smooth • receptors, thrombin

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