Govitrapong P, Hama Y, Pfeiffer R, Ebadi M
Department of Pharmacology, University of Nebraska College of Medicine, Omaha 68105.
J Pineal Res. 1989;6(1):17-31. doi: 10.1111/j.1600-079x.1989.tb00399.x.
In a previous study, we identified in the bovine pineal gland two [3H]spiroperidol-binding sites with KD values of 0.18 and 2.1 nM and Bmax values of 37 and 630 fmol/mg protein, respectively. In this study, the status of dopamine in the bovine pineal glands was delineated further by measuring the relative concentrations of dopamine and norepinephrine and the relative concentrations of serotonin and melatonin. Furthermore, the presence of 4.0 +/- 0.6 micrograms/dopamine/gm tissue encouraged us to delineate the effects of select dopaminergic receptor agonists and antagonists on the synthesis of melatonin in vivo and on the activity of N-acetyltransferase in the rat pineal gland in culture. The acute administration of haloperidol (3 mg/kg intraperitoneally [ip]) or sulpiride (200 mg/kg ip) increased the concentration of melatonin in the pineal gland from 160.6 +/- 8.18 to 327.6 +/- 45.43 and 306.5 +/- 40.53 pg/gland, respectively. Dopamine exhibited dual effects on the activity of N-acetyltransferase, inhibiting the basal activity at 0.1 microM and stimulating it at 10 microM, and the later effect was blocked by propranolol. D2-dopaminergic receptor agonists such as bromocriptine (4.0 microM) or LY-171555 (10.0 microM) partially attenuated the norepinephrine-induced stimulation of N-acetyltransferase, and these attenuating effects were reversed by D2-dopaminergic antagonists such as haloperidol (10 microM) or domperidone (10 microM). The results of these studies are interpreted to indicate that for the synthesis of melatonin, the pineal D2-dopaminergic receptors may function independently from those of the beta 1-adrenergic receptor sites. Furthermore, the said D2-dopaminergic receptor are amenable to down regulation since the activity of N-acetyltransferase remained unaltered (0.0717 vs. 0.0729 nmol/gland/h) following chronic treatment (4 mg/kg ip/day for 30 days) with bromocriptine.
在先前的一项研究中，我们在牛松果体中鉴定出两个[3H]螺哌啶醇结合位点，其解离常数（KD）值分别为0.18和2.1 nM，最大结合容量（Bmax）值分别为37和630 fmol/mg蛋白质。在本研究中，通过测量多巴胺和去甲肾上腺素的相对浓度以及血清素和褪黑素的相对浓度，进一步明确了牛松果体中多巴胺的状态。此外，每克组织中存在4.0±0.6微克多巴胺，这促使我们研究特定多巴胺能受体激动剂和拮抗剂对体内褪黑素合成以及培养的大鼠松果体中N - 乙酰转移酶活性的影响。急性腹腔注射氟哌啶醇（3 mg/kg）或舒必利（200 mg/kg）可使松果体中褪黑素的浓度分别从160.6±8.18 pg/腺体增加到327.6±45.43 pg/腺体和306.5±40.53 pg/腺体。多巴胺对N - 乙酰转移酶的活性表现出双重作用，在0.1 microM时抑制基础活性，在10 microM时刺激活性，后一种作用可被普萘洛尔阻断。D2 - 多巴胺能受体激动剂如溴隐亭（4.0 microM）或LY - 171555（10.0 microM）部分减弱了去甲肾上腺素诱导的N - 乙酰转移酶刺激作用，而这些减弱作用可被D2 - 多巴胺能拮抗剂如氟哌啶醇（10 microM）或多潘立酮（10 microM）逆转。这些研究结果表明，对于褪黑素的合成，松果体D2 - 多巴胺能受体可能独立于β1 - 肾上腺素能受体发挥作用。此外，上述D2 - 多巴胺能受体易于下调，因为在用溴隐亭进行慢性治疗（4 mg/kg腹腔注射/天，共30天）后，N - 乙酰转移酶的活性保持不变（0.0717对0.0729 nmol/腺体/小时）。
