The effect of pertussis toxin on the growth of vascular smooth muscle cells stimulated by serum or platelet-derived growth factor.

Abstract

The involvement of a Gi- or G(o)-related G-protein as a regulator of the growth of guinea pig thoracic aorta smooth muscle (TASM) cells was studied by investigating the effects of pertussis toxin (PTX) on the growth of these cells. PTX treatment decreased the growth rate of TASM cells by 70-100%. This effect was apparent within 24 h after exposure to the toxin and persisted for at least 10 days after starting the treatment. The effect of the toxin appeared to be the result of the inactivation of a G-protein because 1) TASM cell membranes contained a 40-kilodalton substrate for the toxin in in vitro assays that was absent in membranes prepared from cells pretreated with toxin; and 2) the effect required both the enzymatic component (A-protomer) of the toxin that inactivates Gi/G(o)-related G-proteins and its B-oligomer necessary for binding and internalization of the A-protomer. The effect of the toxin was not due to an increased level of intracellular cAMP brought about by inactivation of a G-protein that normally inhibits adenylyl cyclase activity. Further, the toxin did not merely make some unknown mitogen rate limiting, because neither increasing concentrations of serum in the growth medium nor supplementation with platelet-derived growth factor could overcome its inhibition of TASM cell growth. Instead, some unknown process regulated by a PTX-sensitive G-protein appears to be required for the normal growth of these cells.