Hatt J F, Hanson P J
Division of Biology, Aston University, Birmingham, U.K.
Biochem J. 1988 Nov 1;255(3):789-94. doi: 10.1042/bj2550789.
Histamine (0.5 mM) stimulated the cyclic AMP content of cell suspensions containing greater than 80% parietal cells. Epidermal growth factor (EGF) inhibited this stimulatory effect of histamine, but had no effect on basal cyclic AMP content. The half-maximally effective concentration of EGF for inhibition of histamine-stimulated cyclic AMP was 3.9 nM. The equivalent measurement for the inhibition of histamine-stimulated aminopyrine accumulation was 3.0 nM. Aminopyrine accumulation was measured because it provides an index of the secretory activity of the cell. The cyclic AMP phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) prevented the inhibitory effect of EGF on cyclic AMP content. This effect of IBMX was not caused by its ability to raise cellular cyclic AMP content in the presence of histamine. Prevention by IBMX of the inhibitory action of EGF on histamine-stimulated aminopyrine accumulation had been shown previously [Shaw, Hatt, Anderson & Hanson (1987) Biochem. J. 244, 699-704]. EGF stimulated prostaglandin E2 (PGE2) production in the cell fraction containing greater than 80% parietal cells, with the half-maximally effective concentration being 7.5 nM. EGF was ineffective in stimulating PGE2 production if the cell fraction was depleted of parietal cells (12%), or if 0.5 mM-histamine was added to the enriched parietal-cell fraction. In conclusion, EGF may inhibit histamine-stimulated acid secretion by decreasing the cyclic AMP content of parietal cells. This effect could be mediated by an increase in cyclic AMP phosphodiesterase activity, but it is unlikely to involve an effect of EGF on parietal-cell prostaglandin production.
组胺（0.5 mM）刺激了壁细胞含量超过80%的细胞悬液中的环磷酸腺苷（cAMP）含量。表皮生长因子（EGF）抑制了组胺的这种刺激作用，但对基础cAMP含量没有影响。EGF抑制组胺刺激的cAMP的半数有效浓度为3.9 nM。抑制组胺刺激的氨基比林积累的等效测量值为3.0 nM。测量氨基比林积累是因为它提供了细胞分泌活性的指标。环磷酸腺苷磷酸二酯酶抑制剂3 - 异丁基 - 1 - 甲基黄嘌呤（IBMX）可防止EGF对cAMP含量的抑制作用。IBMX的这种作用不是由其在组胺存在下提高细胞cAMP含量的能力引起的。先前已证明IBMX可防止EGF对组胺刺激的氨基比林积累的抑制作用[Shaw, Hatt, Anderson & Hanson (1987) Biochem. J. 244, 699 - 704]。EGF刺激壁细胞含量超过80%的细胞组分中前列腺素E2（PGE2）的产生，半数有效浓度为7.5 nM。如果细胞组分中壁细胞被耗尽（12%），或者向富含壁细胞的组分中加入0.5 mM组胺，则EGF刺激PGE2产生无效。总之，EGF可能通过降低壁细胞的cAMP含量来抑制组胺刺激的胃酸分泌。这种作用可能是由环磷酸腺苷磷酸二酯酶活性增加介导的，但不太可能涉及EGF对壁细胞前列腺素产生的影响。
