Nowak J Z, Sek B, D'Souza T, Dryer S E
Department of Biogenic Amines, Polish Academy of Sciences, Lodz, Poland.
Neurochem Int. 1995 Dec;27(6):519-26. doi: 10.1016/0197-0186(95)00036-8.
The effects of histamine (HA) and selective HA H1-, H2 and H3-receptor agonists on cyclic AMP formation were investigated in intact chick and duck pineal glands HA potently stimulated the pineal cycle AMP formation. The effect of HA was mimicked fully by N alpha-methylated histamines, and partially by several histaminergic drugs: 2-thiazolylethylamine (H1) amthamine (H2) and R alpha-methyl-histamine (H3). Dimaprit, another selective H2-agonist showed marginal activity. Forskolin highly potentiated the action of HA, and only weakly affected the effects of 2-thiazolylethylamine and amthamine. In the chick pineal, the stimulatory effects of HA and the tested histaminergic drugs were not blocked by mepyramine and thioperamide (H1- and H3-blockers, respectively), but they were antagonized by H2-receptor selective compounds ranitidine and aminopotentidine, which, however, acted in a noncompetitive manner. Another H2-selective blocker zolantidine antagonized the HA effect only when used at very high (30-100 microM) concentrations. In the duck pineal, the stimulatory effect of HA on cyclic AMP production was unaffected by mepyramine (H1), thioperamide (H3), and ranitidine (H2), and only partially inhibited by the H2-blocker aminopotentidine. Electrophysiological experiments revealed that HA is capable of evoking inward currents in most of the tested cells acutely isolated from chick pineal gland. The present findings further indicate that the pharmacological profile of the avian pineal HA receptor, whose stimulation leads to activation of cyclic AMP production, is different from any known HA receptor type (H1, H2, H3), and suggest the existence of either an avian-specific HA receptor, or a novel HA receptor subtype. Electrophysiological data suggest that the pineal HA receptor may be somehow linked to activation of an ionic channel.
研究了组胺（HA）以及选择性HA H1、H2和H3受体激动剂对完整鸡和鸭松果体中环磷酸腺苷（cAMP）生成的影响。HA能有效刺激松果体cAMP的生成。Nα-甲基化组胺可完全模拟HA的作用，几种组胺能药物：2-噻唑基乙胺（H1）、氨甲胺（H2）和Rα-甲基组胺（H3）可部分模拟其作用。另一种选择性H2激动剂二甲双胍表现出微弱活性。福斯高林可高度增强HA的作用，而对2-噻唑基乙胺和氨甲胺的作用影响较弱。在鸡松果体中，HA和受试组胺能药物的刺激作用未被美吡拉敏和硫代哌酰胺（分别为H1和H3受体阻滞剂）阻断，但被H2受体选择性化合物雷尼替丁和氨甲烟腚拮抗，不过它们的作用方式是非竞争性的。另一种H2选择性阻滞剂佐兰替丁仅在非常高的浓度（30 - 100 microM）下才拮抗HA的作用。在鸭松果体中，HA对cAMP生成的刺激作用不受美吡拉敏（H1）、硫代哌酰胺（H3）和雷尼替丁（H2）影响，仅被H2受体阻滞剂氨甲烟腚部分抑制。电生理实验表明，HA能够在从鸡松果体急性分离的大多数受试细胞中诱发内向电流。目前的研究结果进一步表明，禽类松果体HA受体的药理学特征与任何已知的HA受体类型（H1、H2、H3）不同，提示可能存在禽类特异性HA受体或新型HA受体亚型。电生理数据表明，松果体HA受体可能以某种方式与离子通道的激活相关联。
