Synergism between histamine H1- and H2-receptors in the cAMP response in guinea pig brain slices: effects of phorbol esters and calcium.
Synergism between histamine H1- and H2-receptors in the cAMP response in guinea pig brain slices: effects of phorbol esters and calcium.
复制标题
豚鼠脑切片 cAMP 反应中组胺 H1 和 H2 受体之间的协同作用：佛波酯和钙的作用。
作者：
M. Garbarg;J. Schwartz
在豚鼠海马脑片中研究了组胺诱导的cAMP积累刺激中H1和H2受体之间的协同作用。由于H1-受体似乎被耦合到磷脂酰肌醇循环，参与的两个分支的循环在这种协同作用进行了评估，通过使用佛波醇酯和/或通过从外部介质中除去Ca 2+。蛋白激酶C激活剂，4 β-佛波醇12，13-二丁酸酯（4 β-PDB），强烈增强，EC 50为0.2 μ M，由二甲双胍，一种H2-受体激动剂在超最大浓度（0.3 mM）下使用引起的cAMP积累。在Impromidine（一种H2受体激动剂）和组胺存在下也观察到4 β-PDB的作用。4 β-佛波醇12-肉豆蔻酸酯，13-乙酸酯，另一种蛋白激酶C激活剂，也以浓度依赖性方式增强二甲双胍的作用，尽管效力低于4 β-PDB。相反，4 α-佛波醇或佛波醇酯，4 α-佛波醇12，13-二癸酸酯或4-O-甲基佛波醇12-肉豆蔻酸酯，13-乙酸酯，都对蛋白激酶C无活性，没有增强作用。2-噻唑基乙胺（2-TEA），一种主要的H1受体激动剂，增加了由二甲双胍（0.3 mM）诱导的刺激，并且这种反应在最大浓度（1 μ M）的4 β-PDB存在下进一步增强。甲吡胺（0.1 μ M）拮抗H1受体介导的作用，以及存在的情况下，4 β-PDB。佛波醇酯没有显著改变2-TEA的EC 50或其作用的大小。在没有佛波醇酯的情况下，从孵育介质中除去Ca 2+并没有改变0.3 mM dimaeylate引起的反应，但减少了50%的反应，以一个超大浓度的2-TEA。当EGTA加入到无钙培养基中时，这种效果更加明显。2-TEA的EC 50值在不存在Ca 2+的情况下仅略微改变（180 +/-20 μ M，相比之下在2.6 mM Ca 2+存在下为70 +/-4 μ M）。在4 β-PDB（1 μ M）的存在下，去除Ca 2+，特别是在EGTA的存在下，不影响或轻微增加对二甲双胍的反应，但仍然强烈降低对2-TEA的反应。Ca 2+离子载体A 23187（10 μ M）显示出模拟2-TEA的增强作用的趋势。（400字处截断摘要）
The synergism between H1- and H2-receptors in the histamine-induced stimulation of cAMP accumulation was studied in slices from guinea pig hippocampus. Since H1-receptors appear to be coupled to the phosphatidylinositol cycle, the participation of the two branches of the cycle in this synergism was assessed by using phorbol esters and/or by removing Ca2+ from the external medium. The protein kinase C activator, 4 beta-phorbol 12,13-dibutyrate (4 beta-PDB), strongly potentiated, with an EC50 of 0.2 microM, the accumulation of cAMP elicited by dimaprit, an H2-receptor agonist used at supramaximal concentration (0.3 mM). The effect of 4 beta-PDB was also observed in the presence of impromidine, an H2-receptor agonist, and histamine. 4 beta-Phorbol 12-myristate, 13-acetate, another protein kinase C activator, also potentiated the effect of dimaprit in a concentration-dependent manner although less potently than 4 beta-PDB. In contrast, 4 alpha-phorbol or the phorbol esters, 4 alpha-phorbol 12,13-didecanoate or 4-O-methylphorbol 12-myristate, 13-acetate, all inactive on protein kinase C, had no potentiating effect. 2-Thiazolylethylamine (2-TEA), a predominantly H1-receptor agonist, increased the stimulation induced by dimaprit (0.3 mM), and this response was further enhanced in the presence of 4 beta-PDB in maximal concentration (1 microM). Mepyramine (0.1 microM) antagonized the H1-receptor-mediated effect in the absence as well as the presence of 4 beta-PDB. The phorbol ester did not significantly alter the EC50 of 2-TEA or the magnitude of its effect. In the absence of phorbol esters, removal of Ca2+ from the incubation medium did not change the response elicited by 0.3 mM dimaprit but reduced by 50% the response to a supramaximal concentration of 2-TEA. This effect was more marked when EGTA was added in the Ca2+-free medium. The EC50 value of 2-TEA was only slightly modified in the absence of Ca2+ (180 +/- 20 microM as compared with 70 +/- 4 microM in the presence of 2.6 mM Ca2+). In the presence of 4 beta-PDB (1 microM), removal of Ca2+, particularly in the presence of EGTA, did not affect or slightly increased the response to dimaprit, but still strongly reduced the response to 2-TEA. The Ca2+ ionophore A 23187 (10 microM) showed a tendency to mimic the potentiating effect of 2-TEA.(ABSTRACT TRUNCATED AT 400 WORDS)