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

• Published in: The Journal of pharmacology and experimental therapeutics 2003-01, Vol.304 (1), p.294-300
• Main Authors: Adegunloye, Banji, Lamarre, Eric, Moreland, Robert S
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Carotid Arteries - drug effects; Contractile Proteins - metabolism; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; Histamine - pharmacology; In Vitro Techniques; Muscle Contraction - drug effects; Muscle Relaxants, Central - pharmacology; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - drug effects; Myosin Light Chains - metabolism; Myosins - metabolism; Phosphorylation - drug effects; Quinine - pharmacology; Swine
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.102.042101

This report contains results of studies designed to determine whether quinine has direct effects on myofilament Ca 2+ sensitization in addition to effects on Ca 2+ . Quinine decreased the EC 50 value and maximal contraction of intact arterial strips to histamine. Incubation of arterial strips with indomethacin or 1 H -[1,2,4]oxadiazole[4,3-α]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 Ca 2+ -induced contraction in α-toxin permeabilized strips, but not the Ca 2+ -induced contraction in Triton X-100 permeabilized strips. Pretreatment of the α-toxin permeabilized strips with quinine before stimulation with guanosine-5′- O -(3-thio)triphosphate (GTPγS) did not have any effect on the response. In conclusion, quinine inhibited Ca 2+ -dependent contractions of the α-toxin permeabilized strips, which retain modulatory pathways both upstream and downstream from the contractile proteins but did not inhibit GTPγS-dependent contraction of the α-toxin permeabilized preparation important in upstream modulation of the contraction. Moreover, quinine did not inhibit the Ca 2+ -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.