Meltzer H Y, Simonovic M, Gudelsky G A
J Pharmacol Exp Ther. 1983 Jan;224(1):21-7.
It was recently proposed that yohimbine (YOH), an indole alkaloid with multiple pharmacological effects, is an antagonist of the D2 dopamine (DA) receptor. Because the pituitary DA receptor involved in the inhibition of prolactin (PRL) secretion is the prototypic D2 receptor, we examined the effect of YOH on PRL secretion in male rats. YOH produced marked, dose-dependent and sustained increases in plasma PRL levels. However, YOH did not block the inhibitory effect of DA on PRL release from rat pituitary glands in vitro, did not displace [3H]spiperone from bovine pituitary membranes and had no effect on the concentration of DA in pituitary stalk plasma of anesthetized rats, suggesting that the stimulation of PRL release by YOH is not due to its antidopaminergic effects. Clonidine, an alpha-2 adrenergic agonist, produced a partial, non-dose-dependent inhibition of the YOH-induced rise in serum PRL levels. Two antagonists of the H1 histamine receptor, diphenhydramine and promethazine, markedly antagonized the PRL-releasing effect of YOH, but another H1 blocker, chlorpheniramine, and an H2 antagonist, metiamide, had no effect. Serotonin receptor blockers, cyproheptadine, mianserin and pizotifen, and the opiate antagonist, naloxone, also had no effect on the PRL response to YOH. Nevertheless, the PRL-releasing effect of YOH was potentiated 24 hr after the administration of reserpine or para-chlorophenylalanine, an inhibitor of serotonin synthesis. Thus, the mechanisms by which YOH stimulates rat PRL secretion has has not been fully elucidated. It is possible that YOH may stimulate PRL secretion by a novel mechanism, possibly through the intervention of a PRL-releasing factor.
最近有人提出，育亨宾（YOH）是一种具有多种药理作用的吲哚生物碱，是D2多巴胺（DA）受体的拮抗剂。由于参与抑制催乳素（PRL）分泌的垂体DA受体是典型的D2受体，我们研究了YOH对雄性大鼠PRL分泌的影响。YOH使血浆PRL水平显著、剂量依赖性且持续升高。然而，YOH在体外并未阻断DA对大鼠垂体PRL释放的抑制作用，未从牛垂体膜上置换出[3H]螺哌隆，且对麻醉大鼠垂体柄血浆中DA的浓度无影响，这表明YOH对PRL释放的刺激并非因其抗多巴胺能作用。可乐定是一种α-2肾上腺素能激动剂，对YOH诱导的血清PRL水平升高产生部分、非剂量依赖性的抑制作用。两种H1组胺受体拮抗剂苯海拉明和异丙嗪显著拮抗YOH的PRL释放作用，但另一种H1阻滞剂氯苯那敏和一种H2拮抗剂甲硫米特则无此作用。5-羟色胺受体阻滞剂赛庚啶、米安色林和匹莫齐特以及阿片拮抗剂纳洛酮对YOH引起的PRL反应也无影响。然而，在给予利血平或5-羟色胺合成抑制剂对氯苯丙氨酸后24小时，YOH的PRL释放作用增强。因此，YOH刺激大鼠PRL分泌的机制尚未完全阐明。有可能YOH可能通过一种新机制刺激PRL分泌，可能是通过一种PRL释放因子的干预。
