The objective of the present studs was to investigate if MAPK can be activated by a non-receptor agonist KCI, which depolarizes membrane to increase intracellular Ca2- and contracts cerebral arteries. Rabbit basilar arteries were used in isometric tension and western blot analysis studies. KCI produced a concentration-dependent contraction and an elevation of phospho-MAPK. which can be abolished by nicardipine. a voltage-dependent Ca2- channel blocker. and by PD98059 or U0126. MAPK kinase inhibitors. Thus, MAPK can be activated by the elevation of intracellular Ca2-. independent of the activation of either G-protein coupled receptors or receptor tyrosine kinase. KCI which not only depolarizes membrane potentials. opens voltage-dependent Ca2-, and increases intracellular Ca2+, but also. probable by elevation of intracellular Ca2-. triggers the activation of MAPK which seems responsible for a predominant part of the contraction of KCI in the rabbit basilar arteries. (C) 2002 Elsevier Science (USA). All rights reserved.