Savage A O, Akinlalu C A
Arch Int Pharmacodyn Ther. 1985 Jul;276(1):163-76.
The actions of quinine on the rat isolated rectum was studied. Quinine (2.5 X 10(-5) - 2.5 X 10(-4) M) initiated rhythmic phasic contractions (RPC) which were prevented by verapamil, lanthanum, indomethacin or Ca2+-withdrawal, but were unaffected by tetrodotoxin, L-propranolol, phentolamine, or atropine. Higher quinine concentrations (2.5 X 10(-4) - 10(-3) M) relaxed the rat rectum and inhibited the RPC induced by lower concentrations. Exposure to high Ca2+-Tyrode solution (6 Ca2+-Tyrode) increased the baseline tone of the muscle. Under this condition, quinine (2.5 X 10(-4) - 10(-3) M), but not lower concentrations relaxed the muscle. Quinine (2.5 X 10(-5) - 10(-3) M) concentration-dependently inhibited KCl and acetylcholine-induced contractions, but more readily blocked KCl than acetylcholine-induced responses; the inhibitory effect of quinine against KCl, but not acetylcholine, was largely reversed by increasing the Ca2+ concentration of the Tyrode solution. It is concluded that quinine-induced RPC occurred independently of adrenergic or cholinergic mechanisms, and are likely to be due to enhanced Ca2+ influx into the rectum, while the relaxation encountered with higher concentrations may be due to inhibition by quinine of transmembranal Ca2+ influx. Evidence was obtained that quinine may preferentially inhibit Ca2+ influx through a pathway linked to high K+ depolarisation.
研究了奎宁对大鼠离体直肠的作用。奎宁(2.5×10⁻⁵ - 2.5×10⁻⁴ M)引发节律性相性收缩(RPC),维拉帕米、镧、吲哚美辛或去除Ca²⁺可阻止这种收缩,但河豚毒素、L-普萘洛尔、酚妥拉明或阿托品对其无影响。更高浓度的奎宁(2.5×10⁻⁴ - 10⁻³ M)可使大鼠直肠松弛,并抑制较低浓度奎宁诱导的RPC。暴露于高Ca²⁺-台氏液(6 Ca²⁺-台氏液)可增加肌肉的基础张力。在此条件下,奎宁(2.5×10⁻⁴ - 10⁻³ M)可使肌肉松弛,但较低浓度则无此作用。奎宁(2.5×10⁻⁵ - 10⁻³ M)浓度依赖性地抑制KCl和乙酰胆碱诱导的收缩,但对KCl诱导反应的阻断作用比对乙酰胆碱诱导反应的阻断作用更明显;通过增加台氏液中的Ca²⁺浓度,可在很大程度上逆转奎宁对KCl而非乙酰胆碱的抑制作用。结论是,奎宁诱导的RPC独立于肾上腺素能或胆碱能机制发生,可能是由于Ca²⁺流入直肠增加所致,而较高浓度时出现的松弛可能是由于奎宁抑制跨膜Ca²⁺流入。有证据表明,奎宁可能优先通过与高K⁺去极化相关的途径抑制Ca²⁺流入。