Quinine inhibits vascular contraction independent of effects on calcium or myosin phosphorylation.
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-alpha]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 alpha-toxin permeabilized strips, but not the Ca2+-induced contraction in Triton X-100 permeabilized strips. Pretreatment of the alpha-toxin permeabilized strips with quinine before stimulation with guanosine-5'-O-(3-thio)triphosphate (GTPgammaS) did not have any effect on the response. In conclusion, quinine inhibited Ca2+-dependent contractions of the alpha-toxin permeabilized strips, which retain modulatory pathways both upstream and downstream from the contractile proteins but did not inhibit GTPgammaS-dependent contraction of the alpha-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.
Adegunloye
Banji
B
Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.
Lamarre
Eric
E
Moreland
Robert S
RS
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002339:Carotid Arteries / Q000187:drug effects; D003285:Contractile Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D018994:Myosin Light Chains / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011803:Quinine / Q000494:pharmacology*; D013552:Swine
D003285:Contractile Proteins; D009125:Muscle Relaxants, Central; D018994:Myosin Light Chains; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006632:Histamine; D011803:Quinine; D009218:Myosins; D002118:Calcium