REGULATION OF ISOTONIC SHORTENING VELOCITY BY 2ND MESSENGERS IN TRACHEAL SMOOTH-MUSCLE

Evidence suggests that the mechanical behavior of smooth muscle tissue s is regulated by Ca2+-dependent changes in the phosphorylation of the 20,000-Da light chain of myosin (MLC). However, alternative mechanism s activated by specific kinases may be involved in regulating the shor tening velocity in some smooth muscle tissues. To determine how the ac tivation of protein kinases A or C affects the regulation of the short ening velocity in canine tracheal smooth muscle, we evaluated the effe cts of forskolin (10(-5) M) and phorbol 12,13-dibutyrate (PDBu, 3 x 10 (-6) M) on active stress, intracellular Ca2+ ([Ca2+](i)), MLC phosphor ylation, and isotonic shortening velocity during contractions elicited by 60 mM KCl. Forskolin depressed and PDBu increased active stress, [ Ca2+](i), MLC phosphorylation, and shortening velocity; thus the effec ts of these agents on the shortening velocity may result from changes in Ca2+-dependent MLC phosphorylation. In contrast, the decline in vel ocity that occurred with time during tonic contractions elicited by K depolarization was not associated with significant changes in MLC pho sphorylation; thus the time-dependent changes in shortening velocity m ay be regulated by a mechanism other than MLC phosphorylation.