Kent G N, Jilka R L, Cohn D V
Endocrinology. 1980 Nov;107(5):1474-81. doi: 10.1210/endo-107-5-1474.
Desensitization of hormone-stimulated cAMP response to parathormone, prostaglandin E2, and calcitonin was characterized in isolated bone cells. Osteoclast- and osteoblast-like cells derived from mouse calvaria were incubated for up to 24 h with agents that cause bone resorption (parathormone, prostaglandin E2, or 1,25-dihydroxycholecalciferol) or with calcitonin, which inhibits bone resorption. The cells were then exposed to parathormone, prostaglandin E2, or calcitonin, and cAMP formation was quantified. Homologous desensitization (refractoriness to the second exposure to the same hormone) occurred for each hormone and was essentially complete after 30 min of preincubation. Heterologous desensitization to parathormone could be produced in both cell types by 1,25-dihydroxycholecalciferol and prostaglandin E2, but not by calcitonin. Heterologous desensitization was of lesser magnitude, requiring more than 8 h to reach significant proportions. In contrast, the cAMP response to calcitonin and prostaglandin E2 could not be altered by preincubation with any other hormone. Dibutyryl cAMP or 3-isobutyl-1-methylxanthine, which are bone-resorptive agents, increased cellular cAMP and caused a slowly developing refractoriness to parathormone, prostaglandin E2, and calcitonin. Calcium (5 mM), an agent which mimics the biochemical action of parathormone in the bone cells but does not affect cAMP similarly desensitized the cells to parathormone, but not to calcitonin and only slightly to prostaglandin E2. These data suggest that heterologous desensitization of bone cells to parathormone results from the initiation of resorption by any agent regardless of whether cAMP is formed during activation of the cells. According to this concept, homologous desensitization to parathormone could involve two components: a rapid phase (< 30 min) and a long term phase, possibly stemming from initiation of resorption.
在分离的骨细胞中对激素刺激的环磷酸腺苷（cAMP）对甲状旁腺激素、前列腺素E2和降钙素的脱敏作用进行了表征。从小鼠颅骨分离得到的破骨细胞样和成骨细胞样细胞，用引起骨吸收的药物（甲状旁腺激素、前列腺素E2或1,25 - 二羟胆钙化醇）或抑制骨吸收的降钙素孵育长达24小时。然后将细胞暴露于甲状旁腺激素、前列腺素E2或降钙素，并对cAMP的形成进行定量。每种激素都发生了同源脱敏（对第二次暴露于相同激素的不应性），预孵育30分钟后基本完成。1,25 - 二羟胆钙化醇和前列腺素E2可在两种细胞类型中产生对甲状旁腺激素的异源脱敏，但降钙素不能。异源脱敏程度较小，需要超过8小时才能达到显著比例。相比之下，预先用任何其他激素孵育都不会改变对降钙素和前列腺素E2的cAMP反应。二丁酰cAMP或3 - 异丁基 - 1 - 甲基黄嘌呤是骨吸收剂，可增加细胞内cAMP，并导致对甲状旁腺激素、前列腺素E2和降钙素的缓慢发展的不应性。钙（5 mM）模拟甲状旁腺激素在骨细胞中的生化作用，但不影响cAMP，同样使细胞对甲状旁腺激素脱敏，但对降钙素不脱敏，对前列腺素E2仅轻微脱敏。这些数据表明，骨细胞对甲状旁腺激素的异源脱敏是由任何药物引发的骨吸收导致的，无论细胞激活过程中是否形成cAMP。根据这一概念，对甲状旁腺激素的同源脱敏可能涉及两个成分：一个快速阶段（<30分钟）和一个长期阶段，可能源于骨吸收的启动。
