Di Paolo T, Bernier M A
School of Pharmacy, Laval University, Québec, Ste-Foy, Canada.
Biochem Pharmacol. 1988 Jun 15;37(12):2373-9. doi: 10.1016/0006-2952(88)90363-2.
The agonist high- and low-affinity states of the dopamine (DA) receptor were investigated with apomorphine competition for [3H]spiperone binding to DA receptors in 7315a tumors grown in intact female rats, while the antagonist site was investigated with saturation of [3H]spiperone binding. Such as for the intact pituitary, the antagonist binding site density in 7315a tumors was not affected by NaCl and/or Gpp(NH)p, and its binding affinity was increased in the presence of NaCl. The DA receptor in 7315a tumors existed in high- and low-affinity agonist states, and the two apomorphine sites had similar affinities in tumoral and intact tissue. However, the proportion of the high affinity state was slightly lower in the 7315a tumor compared to intact tissue. Tumor (7315a) growth in ovariectomized rats was slower than in intact animal; chronic 17 beta-estradiol treatment inhibited growth of these tumors. Prolactin (PRL) concentration and density of DA receptors were higher in tumors grown in ovariectomized than in intact female rats, whereas both decreased after 23 days of 17 beta-estradiol treatment. Estradiol treatment decreased the affinity of the high- and the low-apomorphine binding sites, whereas their proportions remained unchanged. Thus, changes of DA receptors and 7315a tumor growth seem to be related; however, their relationship is complex.
采用阿扑吗啡竞争结合法,在完整雌性大鼠体内生长的7315a肿瘤中,研究多巴胺(DA)受体激动剂的高亲和力和低亲和力状态,该方法通过阿扑吗啡竞争结合[³H]螺哌隆与DA受体;同时,采用[³H]螺哌隆结合饱和法研究拮抗剂位点。与完整垂体类似,7315a肿瘤中拮抗剂结合位点密度不受NaCl和/或Gpp(NH)p影响,且在NaCl存在时其结合亲和力增加。7315a肿瘤中的DA受体存在高亲和力和低亲和力激动剂状态,两个阿扑吗啡位点在肿瘤组织和完整组织中的亲和力相似。然而,与完整组织相比,7315a肿瘤中高亲和力状态的比例略低。去卵巢大鼠体内肿瘤(7315a)的生长比完整动物体内慢;慢性17β-雌二醇治疗可抑制这些肿瘤的生长。去卵巢雌性大鼠体内生长的肿瘤中催乳素(PRL)浓度和DA受体密度高于完整雌性大鼠体内生长的肿瘤,而在17β-雌二醇治疗23天后两者均降低。雌二醇治疗降低了高亲和力和低亲和力阿扑吗啡结合位点的亲和力,但其比例保持不变。因此,DA受体的变化与7315a肿瘤生长似乎相关;然而,它们之间的关系很复杂。