Dreux C, Imhoff V, Rossignol B
Laboratoire de Biochimie des Transports Cellulaires, Université Paris-Sud, Orsay, France.
Am J Physiol. 1987 Dec;253(6 Pt 1):C774-82. doi: 10.1152/ajpcell.1987.253.6.C774.
In parotid fragment [3H]protein, secretion induced by substance P was moderate, but strongly Ca dependent. However, secretion induced by isoproterenol was large and Ca independent. Potentiation of protein secretion was observed when substance P (SP) and isoproterenol (ISO) acted together. Addition of 10(-8) M SP caused a shift to the left in the secretion dose-response curve caused by ISO, but did not enhance ISO-induced maximal response. The potentiating effect seems to be a postreceptor event, since it can be mimicked by forskolin (FK), known to induce directly cAMP accumulation, thus bypassing the beta-adrenergic receptor. The synergism described above was, therefore, investigated at the second messenger production level. Stimulation of parotid gland fragments by simultaneous addition of SP plus ISO or FK did not modify cAMP nor inositol trisphosphate (IP3) accumulation induced independently by each secretagogue alone. The ionophore A23187 was also able to potentiate secretion induced by a beta-adrenergic agonist, this effect being totally abolished by external calcium omission, thus suggesting a role for external calcium in this potentiation phenomenon. These results suggest that the potentiation phenomenon observed is a postreceptor event that occurs at a step distal from the second messenger production.
在腮腺组织块中，[3H]蛋白的分泌受P物质诱导时程度中等，但强烈依赖钙离子。然而，异丙肾上腺素诱导的分泌量大且不依赖钙离子。当P物质（SP）和异丙肾上腺素（ISO）共同作用时，观察到蛋白分泌增强。加入10(-8)M的SP会使ISO引起的分泌剂量反应曲线向左移动，但不会增强ISO诱导的最大反应。这种增强作用似乎是一种受体后事件，因为它可以被已知能直接诱导环磷酸腺苷（cAMP）积累从而绕过β-肾上腺素能受体的福斯可林（FK）模拟。因此，在第二信使产生水平对上述协同作用进行了研究。同时加入SP加ISO或FK刺激腮腺组织块，不会改变每种促分泌剂单独诱导的cAMP或肌醇三磷酸（IP3）积累。离子载体A23187也能够增强β-肾上腺素能激动剂诱导的分泌，这种作用在去除细胞外钙离子时完全消失，因此提示细胞外钙离子在这种增强现象中起作用。这些结果表明，观察到的增强现象是一种受体后事件，发生在第二信使产生的下游步骤。
