Possible mechanisms of inhibitory action of protamine on contractile activity of rat aorta.

Experiments were performed to determine possible mechanisms of inhibitory action of protamine chloride on noradrenaline (10 microM)-, KCl (40 mM)-, BaCl2 (1 mM)- and CaCl2 (10 mM)-induced contractions in rat aorta. Protamine, La3+ and gallopamil (D600), inhibited the K+-induced contractions more effectively than the noradrenaline-induced responses on the basis of the concentrations giving 40% inhibition. Lanthanum (1-5 mM) reduced tissue Ca content in both normal and Ca2+-depleted Tris-buffered solutions and produced an increase in 45Ca efflux from the aortic strip into the Ca2+-depleted Tris solution. Protamine (1-5 mg ml-1) reduced tissue Ca content in normal Tris solution, but to a lesser extent than La3+ in the Ca2+-depleted solution. Furthermore, protamine (3 mg ml-1) produced no increase in 45Ca efflux from aorta. These results suggest that protamine chloride may preferentially inhibit the Ca2+ influx stimulated by K+ depolarization and that its inhibitory action on rat aorta may be due to non-specific displacement of the superficially located bound Ca2+ of the cell membrane, which can also be readily removed by treatment with Ca2+-depleted solution.