AGONIST AND MEMBRANE DEPOLARIZATION-INDUCED ACTIVATION OF MAP KINASE IN THE SWINE CAROTID-ARTERY

Caldesmon phosphorylation has been proposed to be involved in regulati on of smooth muscle contraction. Mitogen-activated protein (MAP) kinas e has been suggested to be the caldesmon kinase; stimulation-induced M AP kinase activation in intact vascular smooth muscle, however, has no t been demonstrated. We measured temporal profiles of MAP kinase activ ation in response to histamine stimulation and membrane depolarization in intact swine carotid artery. Phosphotyrosine levels of 42- and 44- kDa MAP kinases were elevated during contraction in response to histam ine or KCl. The temporal profile of MAP kinase activation/inactivation was similar to that for contraction/relaxation of the vascular tissue in response to KCl or histamine stimulation. MAP kinase activated dur ing contractile stimulation phosphorylates caldesmon with a specific a ctivity significantly greater than that for myelin basic protein-(95-9 8). We propose that MAP kinase is activated in response to all forms o f contractile stimulation. We also suggest that activated MAP kinase p hosphorylates and disinhibits the effects of caldesmon on actin-myosin interactions. This disinhibition allows an inherent level of myosin A TPase activity to be expressed.