Regulation of peptide-YY synthesis and secretion in fetal rat intestinal cultures.
The regulation of intestinal peptide-YY (PYY) synthesis and secretion has not been well studied. We have used fetal rat intestinal cells in culture to examine the intra- and extracellular factors controlling the production of PYY. Immunohistochemical analysis demonstrated a distinct population of cells containing immunoreactive PYY (IR-PYY). When examined by HPLC, the IR-PYY stored and secreted by fetal rat intestinal cell cultures eluted as a single moiety with the same elution time as synthetic rat PYY. Pro-PYY mRNA transcript levels and secretion of IR-PYY into the cell medium were increased by activation of protein kinase-A with either a long-acting cAMP analog or forskolin. In contrast, IR-PYY secretion only was stimulated in a synergistic fashion through calcium- and protein kinase-C-dependent pathways (stimulated with A23187 and phorbol myristate acetate, respectively). The intestinal endocrine peptide, gastric inhibitory peptide, and the neurocrine peptide, gastrin-releasing peptide, were found to stimulate IR-PYY secretion in a dose-dependent fashion, with significant effects observed at concentrations as low as 10(-8) and 10(-12) M, respectively (P less than 0.05-0.001). Cholecystokinin and vasoactive intestinal peptide were without effect on IR-PYY secretion at doses of 10(-12)-10(-6) M. The fatty acid sodium oleate and the cholinergic agonist bethanechol were also found to stimulate IR-PYY secretion, each at a concentration of 10(-4) M (P less than 0.001). The results of the present study indicate that the synthesis and secretion of PYY by the rat intestine is under the regulatory control of a wide variety of extracellular agents, mediated by several intracellular signalling pathways.
Brubaker
P L
PL
Department of Physiology, University of Toronto, Ontario, Canada.
Drucker
D J
DJ
Asa
S L
SL
Greenberg
G R
GR
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005576:Colforsin / Q000494:pharmacology; D004357:Drug Synergism; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology; D019886:Gastrin-Releasing Peptide; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000196:embryology*; D010452:Peptide Biosynthesis; D019894:Peptide YY; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010455:Peptides; D012333:RNA, Messenger; D019894:Peptide YY; D005576:Colforsin; D000001:Calcimycin; D005749:Gastric Inhibitory Polypeptide; D019886:Gastrin-Releasing Peptide; D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine