BETA-ADRENERGIC REGULATION OF GAP-JUNCTIONAL INTERCELLULAR COMMUNICATION IN CULTURED RABBIT GASTRIC EPITHELIAL-CELLS

被引:0
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作者
UEDA, F
KAMEDA, Y
YAMAMOTO, O
SHIBATA, Y
机构
来源
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS | 1994年 / 271卷 / 01期
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R9 [药学];
学科分类号
1007 ;
摘要
The effect of a beta-adrenergic agonist, isoproterenol, on gap-junctional intercellular communication (GJIC) and intracellular cyclic AMP (cAMP) content was investigated in cultured rabbit gastric epithelial cells. Isoproterenol rapidly enhanced GJIC determined by the Lucifer yellow transfer at 10(-6) and 10(-5) M but the effect at 10(-6) M was variable. The enhancement of GJIC by 10(-5) M isoproterenol, which disappeared within 10 or 30 min, was inhibited by a beta blocker, propranolol. Isoproterenol (10(-6) M) greatly increased cAMP at 5 min and much more so at 20 min after its addition. Colforsin (also known as forskolin) and 3-isobutyl-1-methylxanthine (IBMX) enhanced GJIC until 16 and 20 min after their addition, respectively. Both colforsin and IBMX increased the cAMP content by a lesser extent than 10(-6) M isoproterenol. Isoproterenol (10(-5) M) inhibited the GJIC enhanced by colforsin or IBMX. Propranolol abolished the inhibition of GJIC by isoproterenol in the presence of IBMX. Both amiloride, an inhibitor of the Na+/H+ exchanger, and nigericin, a K+/H+ antiporter, inhibited the GJIC enhanced by isoproterenol, IBMX, colforsin and irsogladine. An inhibitor of cAMP-dependent protein kinase A, H-89 (N-[2-((3-(4-bromophenyl)-2-propenyl)-amino)-ethyl]-5-isoquinolinesulfonamide) abolished the enhancement of GJlC by colforsin and IBMX but did not abolish that by isoproterenol. From these results, stimulation of beta-adrenergic receptors by isoproterenol seems to act in two opposite directions on GJIC as follows: 1) facilitation of GJIC by the activation of the Na+/H+ exchanger, which elevates intracellular pH, independent of cAMP production in resting cells; and 2) inhibition of GJIC, which has already been activated. In addition, the activation of the Na+/H+ exchanger may play a crucial role in facilitating GJIC.
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页码:397 / 402
页数:6
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