title: Immunocytochemical localization of peptidylglycine alpha-amidating monooxygenase enzymes (PAM) in human endocrine pancreas.
abstract: We studied the distribution of the enzymes that are involved in the post-translational alpha-amidation of regulatory peptides in human endocrine pancreas, using immunocytochemical methods for light and electron microscopy. Immunoreactivity for the two enzymes involved, peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), was located in the periphery of the islets of Langerhans and in ductal endocrine cells. Staining of reverse-face serial sections demonstrated that these immunoreactivities co-localize with glucagon but not with pancreatic polypeptide (PP), insulin, or somatostatin. Double immunogold staining for electron microscopy confirmed the previous results and revealed a different localization for each enzyme inside the secretory granule: PHM is present in the central core of the glucagon-containing granules, whereas PAL is predominantly located near the granule membrane. The existence of an amidated peptide, GLP1, in the A-cells explains the presence of peptidylglycine alpha-amidating monooxygenase enzymes (PAM) in these cells. The absence of the enzymes in the PR-cells raises the possibility that a different form of amidating enzyme may be involved in the post-translational processing of this peptide.
authors.affiliation: Department of Cytology and Histology, University of Navarra, Pamplona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Martínez
authors.forename: L M
authors.initials: LM
authors.lastname: Montuenga
authors.forename: D R
authors.initials: DR
authors.lastname: Springall
authors.forename: A
authors.initials: A
authors.lastname: Treston
authors.forename: F
authors.initials: F
authors.lastname: Cuttitta
authors.forename: J M
authors.initials: JM
authors.lastname: Polak
mesh_terms: D019760:Amidine-Lyases; D000595:Amino Acid Sequence; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000201:enzymology; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005934:Glucagon / Q000032:analysis; D006056:Golgi Apparatus / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000737:chemistry / Q000201:enzymology* / Q000648:ultrastructure; D008190:Lyases / Q000032:analysis*; D016253:Microscopy, Immunoelectron; D006899:Mixed Function Oxygenases / Q000032:analysis*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D010191:Pancreatic Polypeptide / Q000032:analysis; D013004:Somatostatin / Q000032:analysis
chemical_list: D007328:Insulin; D009097:Multienzyme Complexes; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D005934:Glucagon; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; D008190:Lyases; D019760:Amidine-Lyases; C068521:peptidylamidoglycolate lyase