Submandibular enzymatic vasoconstrictor increases DNA and phosphoinositol synthesis by mesenchymal cells.
Submandibular enzymatic vasoconstrictor (SEV, rK9) induces vascular contraction and platelet aggregation by a mechanism requiring intact enzymatic activity. On the basis of a published report demonstrating growth-promoting enzymatic activity in an extract of the rat submandibular gland, we hypothesized that SEV would affect DNA synthesis. Recombinant SEV (rSEV), expressed in a baculovirus system, increased DNA synthesis 3- to 25-fold in Chinese hamster lung (CCL39) fibroblasts and in rabbit and rat vascular smooth muscle cells in a dose-dependent manner dose eliciting 50% of maximal response: 0.1-1 nM); this effect was inhibited by pertussis toxin (PTX). Inactive rSEV failed to enhance DNA synthesis. In CCL39 fibroblasts, rSEV increased total phosphoinositol (PI) formation (6- to 10-fold at 10 nM), which was inhibited 49% by PTX; it was also partially inhibited by the tyrosine kinase inhibitor genistein (33%) but was not affected by the protein kinase C inhibitor bisindolylmaleimide. These results show that rSEV increases DNA synthesis and PI formation in mesenchymal cells in a dose- and enzymatic activity-dependent manner through a pathway partially mediated by a PTX-sensitive G protein. Thus SEV can induce growth-associated responses, perhaps through a protease-activated receptor mechanism.
Carbini
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Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Scicli
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AG
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*
D007295:Inositol Phosphates; D011994:Recombinant Proteins; D004247:DNA; D012697:Serine Endopeptidases; C067805:submandibular enzymatic vasoconstrictor