Submandibular enzymatic vasoconstrictor increases dna and
phosphoinositol synthesis by mesenchymal cells..
Carbini, Luis A., and A. Guillermo Scicli.
Hypertension and Vascular Research Division, Henry Ford Hospital,
Detroit, Michigan 48202
APStracts 3:0417C, 1996.
Submandibular enzymatic vasoconstrictor (SEV, rK9), induces vascular
contraction and platelet aggregation by a mechanism requiring intact
enzymatic activity. Based on 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 (VSMC)
in a dose-dependent manner (ED50: 0.1 - 1 nM); this effect was
inhibited by pertussis toxin. Inactive rSEV failed to enhance DNA
synthesis. In CCL39 fibroblasts rSEV increased total phosphoinositol
formation (6- to 10-fold at 10 nM) which was inhibited by 49% by
pertussis toxin; 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 phosphoinositol formation in mesenchymal
cells in a dose-/enzymatic activity-dependent manner through a
pathway partially mediated by a pertussis toxin-sensitive G protein.
Thus SEV can induce growth-associated responses, perhaps through a
protease-activated receptor mechanism.
Received 19 September 1996; accepted in final form 16 December
1996.
APS Manuscript Number C541-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996