title: PreproPACAP-derived peptides occur in VIP-producing tumours and co-exist with VIP.
abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) is a newly discovered neuropeptide which exists in two biologically active forms: PACAP-38 consisting of 38 amino acids and PACAP-27, a peptide corresponding to the N-terminal 27 amino acids of PACAP-38. Both PACAPs are derived from a 176 amino acid precursor (preproPACAP) which in addition gives rise to a 29 amino acid peptide, designated PACAP-related peptide (PRP). The presence of the three preproPACAP-derived peptides (PACAP-38, PACAP-27 and PRP) in tumour tissue from nine patients with VIP-producing tumours (pancreatic carcinoma, neuroblastoma, ganglioneuroma and pheochromocytoma) and eleven patients with non-VIP-secreting tumours (gastrinoma, glucagonoma, somatostatinoma, neuroblastoma) was examined by specific radioimmunoassays. In seven out of the nine VIP-secreting tumours elevated concentrations of all the three preproPACAP-derived peptides were found compared with normal tissue, while the concentrations in the non-VIP-secreting tumours were within the normal range. PACAP-38 was in all cases the dominating peptide, the concentration ranging from 41 to 3606 pmol/g. When tumour extracts were fractionated on Sephadex G50 column, tricine gel electrophoresis or reverse-phase HPLC immunoreactive components corresponding to synthetic PACAP-38, PACAP-27 and human PRP were identified, suggesting that preproPACAP was fully processed. Immunocytochemical examination showed PACAP-immunoreactive cells in the tumour tissue which also stained for VIP. This co-localization of PACAP and VIP was confirmed by double-staining experiments on the same sections, demonstrating PHM/VIP mRNA and PACAP-immunostaining in the same cells.
authors.affiliation: Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Fahrenkrug
authors.forename: T
authors.initials: T
authors.lastname: Buhl
authors.forename: J
authors.initials: J
authors.lastname: Hannibal
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000737:chemistry / Q000378:metabolism; D005729:Ganglioneuroma / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D009447:Neuroblastoma / Q000737:chemistry / Q000378:metabolism; D009479:Neuropeptides / Q000032:analysis* / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000032:analysis / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000378:metabolism; D010673:Pheochromocytoma / Q000737:chemistry / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011498:Protein Precursors / Q000032:analysis* / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000032:analysis* / Q000378:metabolism
chemical_list: C495401:ADCYAP1 protein, human; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011498:Protein Precursors; D014660:Vasoactive Intestinal Peptide