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Presence of Pituitary Adenylate Cyclase‐Activating Polypeptide Receptors in Y‐79 Human Retinoblastoma Cells
Author(s) -
Olianas M. C.,
Ennas M. G.,
Lampis G.,
Onali P.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67031293.x
Subject(s) - vasoactive intestinal peptide , secretin , receptor , adenylate kinase , adenylyl cyclase , cyclase , secretin family , pituitary adenylate cyclase activating peptide , endocrinology , medicine , neuropeptide , biology , glucagon , chemistry , biochemistry , hormone , secretion
Cytochemical analysis demonstrated that a high percentage of human Y‐79 retinoblastoma cells displayed a specific labeling by the biotinyl derivative of pituitary adenylate cyclase‐activating polypeptide (PACAP), a novel neuropeptide of the secretin‐vasoactive intestinal peptide (VIP) family of peptides. In cell membranes, the two molecular forms of PACAP, the one with 38 (PACAP 38) and the other with 27 (PACAP 27) amino acids, displaced the binding of 125 I‐PACAP 27 with IC 50 values in the picomolar range and increased adenylyl cyclase activity by 100‐fold with EC 50 values of 27 and 180 p M , respectively. VIP, human peptide histidine‐isoleucine, glucagon, and secretin were much less effective and potent in both receptor assays. The PACAP receptor antagonists PACAP 6–27 and PACAP 6–38 and an antiserum directed against the stimulatory G protein G s inhibited the PACAP stimulation of adenylyl cyclase. In intact cells, both PACAPs and VIP failed to stimulate the phosphoinositide hydrolysis, whereas in cell membranes PACAP 38, but not the other peptides, produced a modest increase (40%) of inositol phosphate formation with an EC 50 value of 22 n M . However, this effect was not antagonized by either PACAP 6–38 or PACAP 6–27. These data demonstrate the presence in human Y‐79 retinoblastoma cells of specific PACAP receptors and provide further evidence that PACAP may act as a neurotransmitter/neuromodulator in mammalian retina.