Hirano T, Saluja A, Ramarao P, Lerch M M, Saluja M, Steer M L
Department of Surgery, Beth Israel Hospital, Boston, Massachusetts 02215.
J Clin Invest. 1991 Mar;87(3):865-9. doi: 10.1172/JCI115091.
Lysosomal hydrolases such as cathepsin B are apically secreted from rabbit pancreatic acinar cells via a regulated as opposed to a constitutive pathway. Intravenous infusion of the cholecystokinin analogue caerulein results in highly correlated apical secretion of digestive and lysosomal enzymes, suggesting that they are discharged from the same presecretory compartment (zymogen granules). Lysosomal enzymes appear to enter that compartment as a result of missorting. After 7 h of duct obstruction is relieved, caerulein-stimulated apical secretion of cathepsin B and amylase is increased, but the ratio of cathepsin B to amylase secretion is not different than that following caerulein stimulation of animals never obstructed. These findings indicate that duct obstruction causes an increased amount of both lysosomal and digestive enzymes to accumulate within the secretagogue releasable compartment but that duct obstruction does not increase the degree of lysosomal enzyme missorting into that compartment. Pancreatic duct obstruction causes lysosomal hydrolases to become colocalized with digestive enzymes in organelles that, in size and distribution, resemble zymogen granules but that are not subject to secretion in response to secretagogue stimulation. These organelles may be of importance in the development of pancreatitis.
诸如组织蛋白酶B之类的溶酶体水解酶，是通过一种受调控的途径而非组成型途径，从兔胰腺腺泡细胞顶端分泌的。静脉输注胆囊收缩素类似物雨蛙肽会导致消化酶和溶酶体酶高度相关的顶端分泌，这表明它们是从同一个分泌前区室（zymogen颗粒）排出的。溶酶体酶似乎由于分选错误而进入该区室。在解除7小时的导管阻塞后，雨蛙肽刺激的组织蛋白酶B和淀粉酶的顶端分泌增加，但组织蛋白酶B与淀粉酶分泌的比率与从未阻塞的动物接受雨蛙肽刺激后的比率没有差异。这些发现表明，导管阻塞会导致溶酶体酶和消化酶在促分泌剂可释放区室内积累的量增加，但导管阻塞不会增加溶酶体酶错分到该区室的程度。胰腺导管阻塞会使溶酶体水解酶与消化酶在细胞器中共定位，这些细胞器在大小和分布上类似于zymogen颗粒，但不会因促分泌剂刺激而分泌。这些细胞器可能在胰腺炎的发展中起重要作用。
