Grasl M, Turnheim K
J Physiol. 1984 Jan;346:93-110. doi: 10.1113/jphysiol.1984.sp015009.
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 one-third and appears to be brought about by 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. Hence this current transient seems to be brought about by rheogenic apical Cl efflux. All 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 (a) luminal addition of adenosine is ineffective, (b) nitrobenzylmercaptopurineriboside, a blocker of cellular nucleoside uptake, augments the effect of serosal adenosine, and (c) the intracellular metabolites of adenosine do not mediate the effect. From the rank-order of potency of adenosine and its analogues 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 cyclic AMP and/or cyclic GMP, since the tissue levels of both compounds are rapidly elevated after addition of adenosine and both cyclic AMP and cyclic 8-bromo-GMP are able to mimic the adenosine action.
用脱氧助间型霉素抑制腺苷脱氨酶后，向浆膜侧添加腺苷可增加兔降结肠离体上皮的短路电流（Isc）和组织电导。在有Cl存在的情况下，Isc的这种增加是由于电中性Cl吸收逆转成生电Cl分泌所致。当无Cl时，腺苷对Isc的刺激作用降至三分之一，且似乎是由HCO3分泌引起的。在所有条件下，主动Na转运均保持不变。向浆膜侧添加呋塞米可显著降低腺苷诱导的电解质分泌，且该分泌依赖于组织浆膜侧Na的存在。Na和Cl与基底外侧Cl进入机制相互作用的化学计量比似乎为1:1。在无Na条件下，腺苷引发一种由Cl离子携带且不受呋塞米抑制的电流瞬变。因此，这种电流瞬变似乎是由生电的顶端Cl外流引起的。所有这些发现表明，跨上皮Cl分泌中的传导步骤位于顶端膜。通过向管腔侧添加氨氯吡脒使Na转运细胞超极化并不能增强电解质分泌。腺苷的作用位点是基底外侧膜的细胞外表面，因为（a）向管腔侧添加腺苷无效，（b）细胞核苷摄取阻滞剂硝基苄基巯基嘌呤核糖苷可增强浆膜侧腺苷的作用，以及（c）腺苷的细胞内代谢产物不介导该作用。根据腺苷及其类似物5'-N-乙基甲酰胺腺苷和N6-环己基腺苷的效力排序得出结论，参与电解质分泌的腺苷受体为Ra亚型。茶碱部分抑制分泌作用。腺苷的细胞内介质似乎是环磷酸腺苷（cAMP）和/或环磷酸鸟苷（cGMP），因为添加腺苷后这两种化合物的组织水平迅速升高，且cAMP和环8-溴-GMP都能够模拟腺苷的作用。
