Foreman J C, Norris D B, Rising T J, Webber S E
Br J Pharmacol. 1986 Jan;87(1):37-44. doi: 10.1111/j.1476-5381.1986.tb10154.x.
The effect of forskolin and several H2-agonists was investigated on the activity of adenylate cyclase in homogenates of guinea-pig lung parenchyma. Histamine, 0.1 microM to 1 mM, dimaprit, 1 microM to 10 mM, 4-methyl histamine, 0.1 microM to 10 mM, impromidine, 10 nM to 10 microM and forskolin, 1 nM to 100 microM, all produced a dose-dependent stimulation of adenylate cyclase activity above the basal level. The histamine H1-receptor antagonist mepyramine, 10 microM, and beta-adrenoceptor antagonist propranolol, 10 microM, had no effect on the stimulation by histamine of adenylate cyclase. The dose-response curve for stimulation by histamine of adenylate cyclase was shifted to the right in a dose-dependent manner by increasing concentrations of several H2-antagonists. Schild plots constructed for each H2-antagonist produced straight lines with slopes not significantly different from unity. The equilibrium dissociation constants obtained for the H2-antagonists in this study were similar to those previously reported for inhibition of dimaprit-induced relaxation of the pre-contracted lung strip, inhibition of [3H]-tiotidine binding to homogenates of guinea-pig lung parenchyma and inhibition of histamine-stimulated adenylate cyclase in guinea-pig gastric mucosa.
研究了福斯高林和几种H2激动剂对豚鼠肺实质匀浆中腺苷酸环化酶活性的影响。组胺（0.1微摩尔/升至1毫摩尔/升）、二甲双胍（1微摩尔/升至10毫摩尔/升）、4-甲基组胺（0.1微摩尔/升至10毫摩尔/升）、英普咪定（10纳摩尔/升至10微摩尔/升）和福斯高林（1纳摩尔/升至100微摩尔/升）均能使腺苷酸环化酶活性在基础水平之上产生剂量依赖性刺激。组胺H1受体拮抗剂美吡拉敏（10微摩尔/升）和β肾上腺素能受体拮抗剂普萘洛尔（10微摩尔/升）对组胺刺激腺苷酸环化酶无影响。几种H2拮抗剂浓度增加时，组胺刺激腺苷酸环化酶的剂量反应曲线以剂量依赖性方式右移。为每种H2拮抗剂构建的希尔德图产生的直线斜率与1无显著差异。本研究中获得的H2拮抗剂的平衡解离常数与先前报道的抑制二甲双胍诱导的预收缩肺条舒张、抑制[3H]-替丁与豚鼠肺实质匀浆结合以及抑制豚鼠胃黏膜中组胺刺激的腺苷酸环化酶的平衡解离常数相似。
