Luminal ATP stimulates fluid and HCO3- secretion in guinea-pig pancreatic duct

Luminal ATP stimulates fluid and HCO3- secretion in guinea-pig pancreatic duct
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DOI:
10.1111/j.1469-7793.1999.0551m.x
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发表时间:
1999-09-01
影响因子:
5.5
通讯作者:
Steward, MC
Steward, MC
中科院分区:
医学1区
文献类型:
--
作者:
Ishiguro, H;Naruse, X;Steward, MC

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1. 通过将ATP和UTP应用于豚鼠胰腺分离的胰管基底外侧和管腔表面,研究了嘌呤受体在胰管中的位置及其在调节胰管分泌中的作用。微灌注小叶间管段细胞内Ca2+浓度的变化通过微荧光法测量。通过监测微注射bcecf -右旋糖酐的密封管段的管腔pH和管腔容积来估计液体和HCO3-的分泌。3 .当ATP和UTP (1 μ M)作用于胰管基底膜或管腔膜时,均引起细胞内Ca2+浓度的双相增加。腹腔应用ATP和UTP均可引起体液和HCO3-分泌。对1 μ M ATP或UTP的最大反应约为分泌素引起的反应的75%。相比之下,基底外侧应用ATP或UTP分别抑制了52%和73%的自发分泌,分泌素诱发的分泌分别抑制了41%和38%。这些数据表明,管腔核苷酸可能以自分泌或旁分泌的方式增强导管分泌,而基底外侧核苷酸可能从神经末梢释放,可能具有抑制作用。事实上,根尖和基底外侧的嘌呤受体都能提高细胞内Ca2+,但它们对分泌有相反的作用,这表明额外的信号通路参与其中。
1. The location of purinoceptors in the pancreatic duct and their role in regulating ductal secretion have been investigated by applying ATP and UTP to basolateral and luminal surfaces of pancreatic ducts isolated from the guinea-pig pancreas.2. Changes in intracellular Ca2+ concentration were measured by microfluorometry in microperfused interlobular duct segments. Fluid and HCO3- secretion were estimated by monitoring luminal pH and luminal volume in sealed duct segments microinjected with BCECF-dextran.3. Both ATP and UTP (1 mu M) caused biphasic increases in intracellular Ca2+ concentration in pancreatic duct cells when applied to either the basolateral or luminal membrane.4. Luminal application of both ATP and UTP evoked fluid and HCO3- secretion. The maximum response to 1 mu M ATP or UTP was about 75% of that evoked by secretin. By contrast, basolateral application of ATP or UTP inhibited spontaneous secretion by 52% and 73 %, respectively, and secretin-evoked secretion by 41 % and 38%, respectively.5. The data suggest that luminal nucleotides may act in an autocrine or paracrine fashion to enhance ductal secretion while basolateral nucleotides, perhaps released from nerve terminals, may have an inhibitory effect. The fact that both apical and basolateral Purinoceptors elevate intracellular Ca2+, but that they have opposite effects on secretion, suggests that additional signalling pathways are involved.