Morini G, Kuemmerle J F, Impicciatore M, Grider J R, Makhlouf G M
Department of Physiology, Medical College of Virginia, Richmond.
J Pharmacol Exp Ther. 1993 Feb;264(2):598-603.
Histamine receptors were characterized in muscle cells isolated from the longitudinal muscle layer of guinea pig intestine. Histamine caused concentration-dependent contraction and stimulated significant increases in [Ca++]i (141 +/- 16 nM, P < .001) and cyclic AMP (cAMP) (10.3 +/- 0.5 pmol/10(6) cells, P < .001). The H1 receptor antagonist, mepyramine, inhibited contraction and the increase in [Ca++]i, whereas the H2 receptor antagonist, cimetidine, augmented contraction and the increase in [Ca++]i (277 +/- 31 nM, P < .01) and abolished the increase in cAMP. In cells maximally contracted with a nonhistamine agonist [cholecystokinin octapeptide (CCK)], histamine caused concentration-dependent relaxation when the contractile effect mediated by H1 receptors was blocked with mepyramine; relaxation was inhibited by cimetidine in a concentration-dependent fashion. The effects mediated by H1 and H2 receptors were characterized further in cells in which only one receptor type was preserved by selective receptor protection. In cells in which only H1 receptors were preserved, histamine caused contraction that was inhibited by mepyramine; no relaxation of CCK-induced contraction could be elicited by histamine in the presence of mepyramine. Conversely, in cells in which only H2 receptors were preserved, histamine had little or no contractile effect by itself but caused relaxation of CCK-induced contraction in the absence of mepyramine. We conclude that in, intestinal muscle cells, H1 receptors mediating Ca(++)-dependent contraction coexist with H2 receptors mediating cAMP-dependent relaxation. The effect of histamine reflects activation of dominant H1 receptors as well as of H2 receptors which act to attenuate [Ca++]i and contraction by stimulating an increase in intracellular cAMP.
对从豚鼠肠道纵肌层分离出的肌细胞中的组胺受体进行了表征。组胺引起浓度依赖性收缩，并刺激细胞内钙离子浓度（[Ca++]i）显著升高（141±16 nM，P<.001）和环磷酸腺苷（cAMP）显著升高（10.3±0.5 pmol/10(6) 个细胞，P<.001）。H1受体拮抗剂美吡拉敏抑制收缩以及[Ca++]i的升高，而H2受体拮抗剂西咪替丁增强收缩以及[Ca++]i的升高（277±31 nM，P<.01），并消除cAMP的升高。在用非组胺激动剂[八肽胆囊收缩素（CCK）]使细胞最大程度收缩后，当用美吡拉敏阻断H1受体介导的收缩效应时，组胺引起浓度依赖性舒张；西咪替丁以浓度依赖性方式抑制舒张。通过选择性受体保护仅保留一种受体类型的细胞中，对H1和H2受体介导的效应进行了进一步表征。在仅保留H1受体的细胞中，组胺引起收缩，该收缩被美吡拉敏抑制；在存在美吡拉敏的情况下，组胺不能引起CCK诱导收缩的舒张。相反，在仅保留H2受体的细胞中，组胺本身几乎没有或没有收缩作用，但在不存在美吡拉敏的情况下可引起CCK诱导收缩的舒张。我们得出结论，在肠道肌细胞中，介导钙离子依赖性收缩的H1受体与介导cAMP依赖性舒张的H2受体共存。组胺的作用反映了主要H1受体以及H2受体的激活，H2受体通过刺激细胞内cAMP升高来减弱[Ca++]i和收缩。
