Protein kinase C inhibitors decrease endothelin ETB receptor mRNA expression and contraction during organ culture of rat mesenteric artery

The effect of protein kinase C (PKC) inhibitors on the induction of endothelin ETB receptors during organ culture was examined in isolated segments of the rat mesenteric artery. After 24 It of organ culture, the endothelin ETB receptor agonist sarafotoxin 6c (S6c) induced a strong contraction compared to fresh segments. The contractile response after 24-h organ culture to S6c was studied in presence (30-min preincubation) or absence, after 24-h treatment, of the PKC inhibitors staurosporine, K252a and Ro31-7549. Exposure to staurosporine or K252a in presence and after 24-h treatment reduced the S6c contraction. In contrast, presence of 2-1[1-3(aminopropyl)indol-3-yl]-3(1-methyl-1H-indol-3-yl)maleimide (Ro31-7549), did not affect the S6c-induced contraction, whereas 24-h treatment abolished the increase of contraction. The PKA inhibitor N-(2-[bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide (H89) did not affect the S6c responses. The mRNA expressions of endothelin ETB receptors (analysed with real-time PCR) were abolished after 24-h treatment with the PKC inhibitors. These results suggest that PKC is involved in the endothelin ETB receptor upregulation following organ culture. (C) 2002 Elsevier Science B.V. All rights reserved.