METALLOENDOPEPTIDASE INHIBITORS AND STIMULUS-SECRETION COUPLING IN THE MOUSE EXOCRINE PANCREAS

被引：1

作者：

COLLINS, SP ^{[1
]}

ROBERTS, ML ^{[1
]}

机构：

[1] UNIV ADELAIDE,DEPT PHYSIOL,GPO BOX 498,ADELAIDE,SA 5001,AUSTRALIA

来源：

PANCREAS | 1990年 / 5卷 / 05期

关键词：

1; 10-Phenanthroline; Inositol phospholipids; Metalloendopeptidase; Pancreas; Secretion;

D O I：

10.1097/00006676-199009000-00013

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Inhibitors of metalloendopeptidases interfere with events involving Ca2+ -dependent membrane fusion in a number of cell types. The divalent ion chelating agent 1,10-phenanthroline inhibited pancreatic amylase secretion stimulated by carbachol, cholecystokinin-octapeptide (CCK-8), or bombesin, but detailed studies indicated that this is unlikely to be a result of inhibition of metalloendopeptidase activity. The binding of [3H]7V-methylscopolamine to pancreatic acini was reduced by 1,10-phenanthroline and this would explain the marked inhibition of carbachol-induced amylase secretion by the chelating agent. CCK-8-stimulated hydrolysis of phosphatidylinositol-4,5-bisphosphate was reduced by 1,10-phenanthroline while the binding of CCK-8 to acini was not affected. This inhibition of hydrolysis would explain the inhibition of CCK-8-and bombesin-induced amylase secretion. The metalloendopeptidase substrate carbobenzoxyglycylphenylalanylamide did not affect bombesin-stimulated amylase secretion. Amylase secretion evoked by treating pancreatic acini with the ionophore A23187 or dibutyryl-cyclic AMP was not reduced by 1,10- phenanthroline, indicating a lack of involvement of metalloendopeptidases in the process of exocytosis in this cell type. © 1990 Raven Press, Ltd., New York.

引用

页码：574 / 579

页数：6

共 25 条

[1]

Kirschner R.J., Goldberg A.L., A high molecular weight metalloendoprotease from the cytosol of mammalian cells, J Biol Chem, 258, pp. 967-976, (1983)

[2]

Matsas R., Fulcher I.S., Kenny A.J., Turner A.J., Substance P and [Leu]enkephalin are hydrolysed by an enzyme in pig caudate synaptic membranes that is identical with the endopeptidase of kidney microvilli, Proc Natl Acad Sci USA, 80, pp. 3111-3115, (1983)

[3]

Almenoff J., Orlowski M., Membrane-bound kidney neutral metalloendopeptidases: Interaction with synthetic substrates, natural peptides and inhibitors, Biochemistry, 22, pp. 590-599, (1983)

[4]

Mundy D.I., Strittmatter W.J., Requirement for metalloen-doprotease in exocytosis: Evidence in mast cells and adrenal chromaffin cells, Cell, 40, pp. 645-656, (1985)

[5]

Couch C.B., Strittmatter W.J., Specific blockers of myoblast fusion inhibit a soluble and not the membrane-associated metalloendo-protease in myoblasts, J Biol Chem, 259, pp. 5396-5399, (1984)

[6]

Farach H.A., Mundy D.I., Strittmatter W.J., Lennarz W.L., Evidence for the involvement of metalloendoproteases in the acrosome reaction in sea urchin sperm, J Biol Chem, 262, pp. 5483-5487, (1987)

[7]

Putney J.W., Formation and actions of calcium mobilizing messenger, inositol 1,4,5-trisphosphate, Am J Physiol, 252, pp. G149-G157, (1987)

[8]

Wooten M.W., Wrenn R.W., Phorbol ester induces intracellular translocation of phospholipid/Ca2+-dependent protein kinase C and stimulates amylase secretion in isolated pancreatic acini, FEBS Lett, 171, pp. 183-186, (1984)

[9]

Pandol S.J., Schoeffield M.S., 1,2-Diacylglycerol, protein kinase C, and pancreatic enzyme secretion, J Biol Chem, 261, pp. 4438-4444, (1986)

[10]

Williams J.A., Korc M., Dormer R.L., Action of secretagogues on a new preparation of functionally intact, isolated pancreatic acini, Am J Physiol, 235, pp. E517-E524, (1978)

← 1 2 3 →