Vol. 304, Issue 1, 294-300, January 2003

Quinine Inhibits Vascular Contraction Independent of Effects on Calcium or Myosin Phosphorylation

Banji Adegunloye, Eric Lamarre and Robert S. Moreland

Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania

This report contains results of studies designed to determine whether quinine has direct effects on myofilament Ca²⁺ sensitization in addition to effects on Ca²⁺. Quinine decreased the EC₅₀ value and maximal contraction of intact arterial strips to histamine. Incubation of arterial strips with indomethacin or 1H-[1,2,4]oxadiazole[4,3-]quinoxalin-1-one did not alter quinine inhibition, suggesting that the effect is not mediated via cyclooxygenase or cGMP. Pretreatment of strips with quinine had no effect on the histamine-dependent increases in myosin light chain phosphorylation levels. Quinine inhibited Ca²⁺-induced contraction in -toxin permeabilized strips, but not the Ca²⁺-induced contraction in Triton X-100 permeabilized strips. Pretreatment of the -toxin permeabilized strips with quinine before stimulation with guanosine-5'-O-(3-thio)triphosphate (GTPS) did not have any effect on the response. In conclusion, quinine inhibited Ca²⁺-dependent contractions of the -toxin permeabilized strips, which retain modulatory pathways both upstream and downstream from the contractile proteins but did not inhibit GTPS-dependent contraction of the -toxin permeabilized preparation important in upstream modulation of the contraction. Moreover, quinine did not inhibit the Ca²⁺-dependent contractions of the Triton X-100 permeabilized strips, which are devoid of all modulatory pathways. This suggests that quinine does not act upstream from or directly on the contractile proteins. A more likely site of action may be downstream of the contractile proteins and specifically at the coupling of the contractile proteins with the physiological endpoint of force development.