Yu H X, Turner J T
Department of Pharmacology, School of Medicine, University of Missouri-Columbia.
J Pharmacol Exp Ther. 1991 Dec;259(3):1344-50.
Extracellular nucleotides, acting through P2 purinoceptors, have been implicated in the regulation of ion transporting epithelia, including salivary gland acini. Multiple P2 purinoceptor subtypes have been suggested, including P2X, P2Y and P2U (or nucleotide) subtypes, as well as the P2Z subtype found in rat parotid acinar cells. We investigated responses to ATP, ATP analogs and UTP in transformed human submandibular gland duct cells (HSG-PA), in order to compare duct cell purinoreceptors with those in acinar cells. ATP, UTP and some ATP analogs increased, with different potencies, inositol phosphate accumulation, calcium mobilization and potassium efflux. Nucleotide-stimulated calcium mobilization occurred in the absence of, but was enhanced by, extracellular calcium, and maximal potassium efflux required extracellular calcium. UTP and ATP demonstrated equal potencies of about 1 microM and similar efficacies in eliciting these responses, and identical rank orders of potency for stimulating calcium mobilization and potassium efflux were obtained: UTP = ATP greater than ATP gamma S greater than ADP greater than ADP beta S, with alpha,beta-methylene-ATP and 2-methylthio-ATP having little or no effect. Agents reported to block nucleotide effects in parotid acini were ineffective in HSG-PA cells, and experiments in Mg(++)- and Ca(++)-free medium did not indicate that a form of ATP other than MgATP was the active species at the HSG-PA purinoceptor. The extracellular nucleotide effects were not altered by pertussis toxin. These results indicate the presence of a P2U or nucleotide receptor subtype in HSG-PA submandibular duct cells distinguishable from the P2Z purinoceptor of rat parotid acinar cells, suggesting involvement of multiple nucleotide receptor subtypes in salivary gland regulation.
通过P2嘌呤受体起作用的细胞外核苷酸，已被证明参与包括唾液腺腺泡在内的离子转运上皮的调节。已提出多种P2嘌呤受体亚型，包括P2X、P2Y和P2U（或核苷酸）亚型，以及在大鼠腮腺腺泡细胞中发现的P2Z亚型。我们研究了转化的人下颌下腺导管细胞（HSG-PA）对ATP、ATP类似物和UTP的反应，以便将导管细胞嘌呤受体与腺泡细胞中的受体进行比较。ATP、UTP和一些ATP类似物以不同的效力增加了肌醇磷酸积累、钙动员和钾外流。核苷酸刺激的钙动员在没有细胞外钙的情况下发生，但细胞外钙会增强这种作用，最大钾外流需要细胞外钙。UTP和ATP在引发这些反应方面表现出约1微摩尔的同等效力和相似的效能，并且在刺激钙动员和钾外流方面获得了相同的效力排序：UTP = ATP大于ATPγS大于ADP大于ADPβS，α,β-亚甲基-ATP和2-甲硫基-ATP几乎没有作用或没有作用。据报道能阻断腮腺腺泡中核苷酸作用的试剂在HSG-PA细胞中无效，并且在无镁和无钙培养基中的实验并未表明除MgATP之外的某种ATP形式是HSG-PA嘌呤受体的活性物质。细胞外核苷酸的作用不受百日咳毒素的影响。这些结果表明，HSG-PA下颌下导管细胞中存在一种与大鼠腮腺腺泡细胞的P2Z嘌呤受体不同的P2U或核苷酸受体亚型，提示多种核苷酸受体亚型参与唾液腺调节。
