Contraction of rat thoracic aorta strips induced by phorbol 12-myristate 13-acetate

Abstract

Phorbol 12-myristate 13-acetate (PMA) induced a slow and progressive increase in tension of rat thoracic aorta strips in the presence of extracellular Ca2+. Complete relaxation could not be obtained in Ca2+-free buffer containing 1 mM ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA) and 10(-7) M PMA. In the absence of extracellular Ca2+, PMA (10(-7) M) induced a small but sustained contraction which was not altered by the addition of another 2 mM EGTA and 3 X 10(-5) M verapamil. Papaverine (10(-4) M) relaxed the PMA-induced contraction to the base line, but phentolamine (10(-5) M), cyproheptadine (10(-5) M), atropine (10(-5) M) and tetrodotoxine (10(-6) M) did not change the contraction. Ca2+-depleted muscle strips, prepared by four repeated applications of 10(-7) M norepinephrine in Ca2+-free buffer, were contracted by 10(-7) M PMA, but at a lower maximum tension than nontreated strips. The action of PMA on rat aorta strips in Ca2+-free buffer did not require the presence of the adventitial layer or endothelial cells. These results suggest that PMA may induce activation of protein kinase C and smooth muscle contraction in the absence of extracellular Ca2+, without an increase in myoplasmic Ca2+.