PERTUSSIS-TOXIN-SENSITIVE ENDOTHELIN-1 COUPLING TO INOSITOL PHOSPHATEFORMATION VIA A GTP-BINDING PROTEIN - COMPARISON IN SHR AND WKY CULTURED AORTIC SMOOTH-MUSCLE CELLS

The effects of pertussis toxin on endothelin-1 and noradrenaline coupl ing to inositol phosphate (IP) formation was investigated in cultured aortic smooth muscle cells from 14 week SHR and WKY rats. Endothelin-1 (10(-6)M) stimulated IP formation was decreased in cells from SHR com pared to WKY (WKY 1117+/-157, SHR 668+/-85% of basal). Pre-incubation with pertussis toxin produced a significant and similar reduction in e ndothelin stimulated IP production in both SHR (54% reduction) and WKY (55%). However, the observed reduction in endothelin-1 stimulated IP accumulation was still apparent in SHR when compared to WKY. Pertussis toxin preincubation followed by removal of extracellular calcium redu ced further the endothelin responses by similar amounts in SHR and WKY cells, but SHR stimulated IP formation remained significantly decreas ed compared to WKY. The extent of pertussis toxin ADP-ribosylation of G(i alpha) was similar in both SHR and WKY cells. Endothelin-1 produce d a reduction in the extent of ADP-ribosylation of G(i alpha) and this was of similar magnitude in both SHR and WKY cell membranes. In contr ast, noradrenaline stimulated IP formation was unaffected by pertussis toxin pre-incubation. It was concluded that SHR cells do not appear t o have an alteration in endothelin-1 activated, pertussis toxin sensit ive G-protein coupling to IP formation or in the dependence of inosito l phosphate formation on extracellular calcium.