LIVER ALCOHOL AND ALDEHYDE DEHYDROGENASE: INHIBITION AND POTENTIATION BY HISTAMINE AGONISTS AND ANTAGONISTS

1. The in vitro effects of histamine, some other Hi- and H₂-receptor agonists and some antagonists were studied on the specific activities and kinetics of rat liver alcohol dehydrogenase (ADH), and cytoplasmic and mitochondrial liver aldehyde dehydrogenase (ALDH). 2. Histamine (H₁- and H₂-agonist) non-competitively inhibited ADH and ALDH, 2-(2-aminoethyl) pyridine (Hi-receptor agonist) non-competitively inhibited ADH. There were no changes of cytoplasmic and mitochondrial liver ALDH activities in the presence of 2-(2-aminoethyl) pyridine. 3. Betazole (H₂-receptor agonist) produced a competitive inhibition of mitochondrial ALDH but not of ADH or cytoplasmic ALDH. 4. Diphenhydramine (H₁-receptor antagonist) non-competitively inhibited ADH at a lower concentration. It stimulated mitochondrial ALDH activity without changes in cytoplasmic ALDH from control values. 5. Burimamide (H₂-receptor antagonist) produced a biphasic and dose-dependent stimulation and non-competitive inhibition of ADH and it non-competitively inhibited ALDH in both cytoplasmic and mitochondrial fractions. Metiamide (H₂-receptor antagonist) non-competitively inhibited all ADH and ALDH of both liver fraction studied. 6. It is concluded that liver ADH and ALDH activity can be altered by compounds which affect both Hi- and H₂-histamine receptors and that these compounds may cause an in vivo potentiation and/or reduction of the toxic effect of ethanol.     

内源性组胺经突触前组胺H_3受体介导抑制心交感神经冲动传递

采用豚鼠离体右心房标本观察内源性组胺对心交感神经冲动传递的影响。以组氨酸１ｕｍｏｌ·Ｌ￣（－１）温育右心房标本以增加心肌组胺的合成，１ｈ后施以电场刺激。心房肌正性变力效应较正常降低２６％。雷尼替丁（１ｕｍｏｌ·Ｌ￣（－１））和氯苯吡胺（１ｐｍｏｌ·Ｌ￣（－１））对上述抑制效应无影响。Ｈ＿３受体拮抗剂布立马胺可浓度依赖性地拮抗上述效应。Ｈ＿３受体激动剂（Ｒ）－ａ－甲基组胺则可抑制布立马胺的作用用肥大细胞脱颗粒剂化合物４８－８０温育标本１５ｍｈ。可使电场刺激诱发的正性变力效应增强７５％。结果提示。内源性组胺可能通过交感神经末梢突触前膜组胺Ｈ＿３受体，参予去甲肾上腺素释放的负调节。     

EFFECTS OF HISTAMINE BOLUS INJECTIONS AND CONTINUOUS INFUSIONS ON THE H1- AND H2-RECEPTORS IN THE HINDLIMB VESSELS OF THE RABBIT

1. Hindlimb vascular resistance (HVR) was continuously measured after pharmacological block of the autonomic effectors in unanaesthetized rabbits with previously implanted Doppler ultrasonic flowmeters. 2. Histamine bolus injections caused a dose-related short lived fall in HVR followed by a more sustained rise. The fall was due to H₂-receptor stimulation (blocked by burimamide or metiamide) and the rise to H₁-receptor stimulation (blocked by mepyramine). At the doses of histamine tested the magnitude of the H₁-mediated vasocoiistriction had a larger peak effect than the H₂-mediated vasodilatation. 3. Histamine infusions up to 200 μg kg^?1 min^?1 did not alter HVR significantly but both increases and decreases in HVR were observed after giving H₂- or H₁-antagonists, respectively. 4. From the double reciprocal plots of 1/peak HVR change and 1/dose of histamine the magnitude of the predicted H₁- and H₂-mediated peak HVR effects at large doses were the same. This suggested that the number of H₁-_- and H₂-receptors were similar in the hindlimb vascular bed, in agreement with the infusion data.