Regulation of GH3-cell function via adenosine A1 receptors. Inhibition of prolactin release, cyclic AMP production and inositol phosphate generation.
Regulation of GH3-cell function via adenosine A1 receptors. Inhibition of prolactin release, cyclic AMP production and inositol phosphate generation.
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通过腺苷 A1 受体调节 GH3 细胞功能。
DOI：
10.1042/bj2550069
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Linden,J
中科院分区：
文献类型：
--
作者：
Delahunty,TM;Cronin,MJ;Linden,J
我们研究了腺苷抑制GH 3细胞（大鼠垂体瘤细胞系）泌乳素分泌的机制。催乳素的释放被血管活性肠肽（VIP）和促甲状腺素释放激素（TRH）增强，VIP增加环AMP，TRH增加肌醇磷酸（IPx）。腺苷类似物减少催乳素释放，VIP刺激的环AMP积累和TRH刺激的肌醇磷脂水解和IPx生成。R-N6-phenylisopropyladenosine（R-PIA）对InsP 3产生的抑制作用是快速的（15 s），并且不受添加毛喉素或去除外部Ca 2+的影响。此外，腺苷脱氨酶或有效的腺苷受体拮抗剂，BW-A1433 U，增强VIP的环AMP的积累，表明内源性产生的腺苷张力抑制腺苷酸环化酶。腺苷类似物抑制环AMP和IPx反应的效力顺序（在腺苷脱氨酶存在下测量）为N6-环戊基腺苷大于R-PIA大于5′-N-乙基羧酰胺腺苷。这种等级顺序表明，环AMP和InsP 3的生产抑制介导的腺苷A1受体。对R-PIA的反应被BW-A1433 U（1 μ M）或用百日咳毒素预处理细胞阻断。需要更大量的毒素来消除R-PIA对磷酸肌醇的影响，而不是对环AMP积累的影响。这些数据表明，腺苷，除了抑制环AMP的积累，减少IPx生产在GH 3细胞，可能是通过直接抑制磷酸肌醇水解。
We examined the mechanism by which adenosine inhibits prolactin secretion from GH3 cells, a rat pituitary tumour line. Prolactin release is enhanced by vasoactive intestinal peptide (VIP), which increases cyclic AMP, and by thyrotropin-releasing hormone (TRH), which increases inositol phosphates (IPx). Analogues of adenosine decreased prolactin release, VIP-stimulated cyclic AMP accumulation and TRH-stimulated inositol phospholipid hydrolysis and IPx generation. Inhibition of InsP3 production by R-N6-phenylisopropyladenosine (R-PIA) was rapid (15 s) and was not affected by the addition of forskolin or the removal of external Ca2+. Addition of adenosine deaminase or the potent adenosine-receptor antagonist, BW-A1433U, enhanced the accumulation of cyclic AMP by VIP, indicating that endogenously produced adenosine tonically inhibits adenylate cyclase. The potency order of adenosine analogues for inhibition of cyclic AMP and IPx responses (measured in the presence of adenosine deaminase) was N6-cyclopentyladenosine greater than R-PIA greater than 5′-N-ethylcarboxamidoadenosine. This rank order indicates that inhibitions of both cyclic AMP and InsP3 production are mediated by adenosine A1 receptors. Responses to R-PIA were blocked by BW-A1433U (1 microM) or by pretreatment of cells with pertussis toxin. A greater amount of toxin was required to eliminate the effect of R-PIA on inositol phosphate than on cyclic AMP accumulation. These data indicate that adenosine, in addition to inhibiting cyclic AMP accumulation, decreases IPx production in GH3 cells, possibly by directly inhibiting phosphoinositide hydrolysis.