STIMULATION OF ELECTROLYTE SECRETION IN RABBIT COLON BY ADENOSINE
STIMULATION OF ELECTROLYTE SECRETION IN RABBIT COLON BY ADENOSINE
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DOI：
10.1113/jphysiol.1984.sp015009
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发表时间：
1984-01-01
影响因子：
5.5
通讯作者：
TURNHEIM, K
中科院分区：
文献类型：
--
作者：
GRASL, M;TURNHEIM, K
脱氧共形霉素抑制腺苷脱氨酶后再加入腺苷可增加兔降结肠上皮细胞的短路电流和组织电导。在Cl的存在下，这种增加的Isc的结果从电中性Cl吸收的流变性Cl分泌逆转。当Cl不存在时，腺苷对Isc的刺激作用降低到1/3，并且似乎引起HCO 3分泌。在所有条件下，主动钠运输保持不变。浆膜添加速尿可显着减少腺苷诱导的电解质分泌，并且取决于组织浆膜侧是否存在钠。Na和Cl与基底外侧Cl进入机制的相互作用的化学计量似乎是1：1。在无钠条件下，腺苷激发出由Cl离子携带的电流瞬变，并且不被呋塞米抑制。这种电流瞬变似乎是由流变性顶端Cl流出所带来的。这些研究结果表明，跨上皮Cl分泌的导电步骤驻留在顶端膜。超极化的钠转运细胞管腔此外阿米洛利不增强电解质分泌。腺苷的作用位点是基底外侧膜的细胞外表面，因为腺苷的管腔添加是无效的，细胞核苷摄取的阻断剂硝基苄基巯基嘌呤核苷增强了丝氨酸腺苷的作用，并且腺苷的细胞内代谢产物不介导该作用。从腺苷及其类似物5“-N-乙基甲酰胺腺苷和N6-环己基腺苷的效力的等级顺序可以得出结论，参与电解质分泌的腺苷受体是Ra亚型。茶碱部分抑制分泌作用。腺苷的细胞内介质似乎是cAMP和/或cGMP，因为在加入腺苷后，两种化合物的组织水平迅速升高，cAMP和c8-溴-GMP都能够模拟腺苷的作用。
Serosal addition of adenosine after inhibition of adenosine deaminase with deoxycoformycin increases short-circuit current (Isc) and tissue conductance of isolated epithelia of rabbit descending colon. In the presence of Cl this increase in Isc results from a reversal of electrically neutral Cl absorption to rheogenic Cl secretion. When Cl is absent the stimulating effect of adenosine on Isc is reduced to 1/3 and appears to be brought about HCO3 secretion. Under all conditions active Na transport remains unaltered. Adenosine-induced electrolyte secretion is markedly decreased by serosal addition of furosemide and depends on the presence of Na on the serosal side of the tissue. The stoichiometry of the interaction of Na and Cl with the basolateral Cl entry mechanism appears to be 1:1. Under Na-free conditions adenosine elicits a current transient which is carried by Cl ions and which is not inhibited by furosemide. This current transient seems to be brought about by rheogenic apical Cl efflux. These findings suggest that the conductive step in transepithelial Cl secretion resides in the apical membrane. Hyperpolarization of the Na-transporting cells by luminal addition of amiloride does not enhance electrolyte secretion. The site of action of adenosine is the extracellular surface of the basolateral membrane, because luminal addition of adenosine is ineffective, nitrobenzylmercaptopurineriboside, a blocker of cellular nucleoside uptake, augments the effect of serosal adenosine and the intracellular metabolites of adenosine do not mediate the effect. From the rank-order of potency of adenosine and its analogs 5''-N-ethylcarboxamide adenosine and N6-cyclohexyladenosine it is concluded that the adenosine receptors involved in electrolyte secretion are of the Ra subtype. Theophylline partially inhibits the secretory effect. The intracellular mediator of adenosine appears to be cAMP and/or cGMP, since the tissue levels of both compounds are rapidly elevated after addition of adenosine and both cAMP and c8-bromo-GMP are able to mimic the adenosine action.