Dehaye J P
Service de Biochimie générale et humaine, Université libre de Bruxelles.
Bull Mem Acad R Med Belg. 1999;154(6 Pt 2):355-61.
Exocrine secretions proceed in two phases which can be studied individually in submandibular glands. We have investigated the response to neuropeptides and purinergic agonists of rat submandibular glands. Pituitary Adenylate Cyclase Activating Peptide (PACAP), an analog of VIP increased the intracellular concentration of cyclic AMP in acinar cells. PACAP also stimulated the activity of the Na(+)-K(+)-2Cl(-)-cotransporter. Extracellular ATP increased the [Ca2+]i in ductal cells. Two distinct receptors were involved in this response. A metabotropic purinergic receptor of the P2Y1 type raised the cellular concentration of IP3 after activating a phospholipase C. The second component of the purinergic response involved an ionotropic P2X7 receptor. After binding an agonist, this receptor formed a non-specific cation channel permeant to calcium and manganese, highly sensitive to inhibition by nickel. Two phospholipases A2 were activated following the occupancy of this receptor. The calcium-independent enzyme triggered kallikrein secretion in response to extracellular ATP. In conclusion, neuropeptides and purinergic agonists activate the acinar and ductal phases of the salivary secretion and are therefore promising candidates for the development of new sialagogues for therapeutic use.
外分泌过程分为两个阶段，可在下颌下腺中分别进行研究。我们已经研究了大鼠下颌下腺对神经肽和嘌呤能激动剂的反应。垂体腺苷酸环化酶激活肽（PACAP），一种血管活性肠肽类似物，可增加腺泡细胞内的环磷酸腺苷浓度。PACAP还刺激了Na(+)-K(+)-2Cl(-)共转运体的活性。细胞外ATP增加了导管细胞内的[Ca2+]i。两种不同的受体参与了这一反应。P2Y1型代谢型嘌呤能受体在激活磷脂酶C后提高了细胞内的IP3浓度。嘌呤能反应的第二个成分涉及离子型P2X7受体。在结合激动剂后，该受体形成了一个对钙和锰通透的非特异性阳离子通道，对镍的抑制高度敏感。该受体被占据后，两种磷脂酶A2被激活。钙非依赖性酶响应细胞外ATP触发激肽释放酶的分泌。总之，神经肽和嘌呤能激动剂激活了唾液分泌的腺泡和导管阶段，因此是开发用于治疗的新型催涎剂的有前途的候选药物。
