SIGNAL TRANSDUCTION PATHWAYS IN CONSTRICTION OF THE BASILAR ARTERY INVIVO

We examined effects of a putative myosin light chain kinase inhibitor in the cerebral circulation in vivo. In anesthetized rats, diameter of basilar arteries was measured through a cranial window (control, 232+/-10-mu-m, mean+/-SEM). Vessel diameter was measured during topical application of agonists and antagonists. ML-7, which has been reported to compete with adenosine triphosphate for binding to the catalytic site on myosin light chain kinase, attenuated vasoconstriction in response to prostaglandin F2-alpha (10(-6) M; -22+/-1% before versus -14+/-1% and -3+/-2% during ML-7, 10(-7) and 10(-6) M, respectively; p<0.05). ML-7 (10(-6) M) did not affect baseline diameter. Responses to serotonin (10(-8) M) and phorbol 12,13-dibutyrate (10(-8) M) were not attenuated by ML-7. Thus, constriction of the basilar artery induced by prostaglandin F2-alpha in vivo is attenuated by an inhibitor of myosin light chain kinase.