Menozzi D, Vinayek R, Jensen R T, Gardner J D
Digestive Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J Biol Chem. 1991 Jun 5;266(16):10385-91.
First incubating dispersed acini from rat pancreas with monensin, a cation ionophore that can inhibit recycling of receptors, inhibited binding of 125I-cholecystokinin 8 (125I-CCK-8) measured during a second incubation by as much as 50%. A maximal effect of monensin required 90 min of first incubation. Detectable inhibition of binding of 125I-CCK-8 occurred with 300 nM monensin, and inhibition increased progressively with concentrations of monensin up to 25 microM. Pancreatic acini possess two classes of receptors that bind 125I-CCK-8. One class has a high affinity (Kd = 461 pM) and a low capacity for CCK (512 fmol/mg DNA); the other class has a low affinity (Kd = 47 nM) and a high capacity for CCK (18 pmol/mg DNA). First incubating acini with monensin caused an 84% decrease in the number of high affinity CCK receptors with no change in the number of low affinity CCK receptors or the values of Kd for either class of receptors indicating that there is recycling of high affinity CCK receptors but not low affinity CCK receptors. First incubating acini with monensin did not alter CCK-stimulated amylase secretion indicating that in contrast to previous conclusions, occupation of low affinity CCK receptors mediates CCK-stimulated enzyme secretion. Moreover, the biphasic dose-response curve for CCK-stimulated enzyme secretion from monensin-treated acini suggests that pancreatic acini also possess a third, previously unrecognized class of very low affinity CCK receptors.
首先用莫能菌素（一种可抑制受体再循环的阳离子离子载体）孵育大鼠胰腺分散的腺泡，在第二次孵育期间测定的125I - 胆囊收缩素8（125I - CCK - 8）的结合受到抑制，抑制程度高达50%。莫能菌素的最大效应需要第一次孵育90分钟。300 nM的莫能菌素即可检测到对125I - CCK - 8结合的抑制，并且随着莫能菌素浓度增加至25 microM，抑制作用逐渐增强。胰腺腺泡具有两类结合125I - CCK - 8的受体。一类具有高亲和力（Kd = 461 pM）且对CCK的结合能力低（512 fmol/mg DNA）；另一类具有低亲和力（Kd = 47 nM）且对CCK的结合能力高（18 pmol/mg DNA）。先用莫能菌素孵育腺泡导致高亲和力CCK受体数量减少84%，而低亲和力CCK受体数量或两类受体的Kd值均无变化，这表明高亲和力CCK受体存在再循环，而低亲和力CCK受体不存在再循环。先用莫能菌素孵育腺泡并未改变CCK刺激的淀粉酶分泌，这表明与之前的结论相反，低亲和力CCK受体的占据介导了CCK刺激的酶分泌。此外，莫能菌素处理的腺泡中CCK刺激酶分泌的双相剂量反应曲线表明，胰腺腺泡还存在第三类此前未被认识的极低亲和力CCK受体。
