Transcription, expression and tissue binding in vivo of INGAP and INGAP-related peptide in normal hamsters

BORELLI MI; DEL ZOTTO H; FLORES LE; GARCÍA ME; BOSCHERO A; GAGLIARDINO JJ

REGULATORY PEPTIDES

Elsevier BV

Año: 2007 vol. 140 p. 192 - 197

0167-0115

We studied islet neogenesis-associated protein (INGAP) transcription and its immunocytochemical presence in and binding in vivo of 125I-tyrosylated INGAP pentadecapeptide (125I-T-INGAP-PP) to different normal male hamster tissues. 125I-T-INGAP-PP was injected intraperitoneally with or without unlabeled T-INGAP-PP (0-1 mg/100 g bw), drawing blood samples at different times after injection; radioactivity was measured in serum, brain, skeletal muscle, dorsal root ganglia, liver, kidney, small intestine and pancreas samples, expressing results as organ:serum ratio. INGAP transcription (RT-PCR) and immunopositive cells were investigated in liver, kidney, brain, small intestine and pancreas. Total serum radioactivity increased progressively as a function of time; whereas 71% of this activity was displaced by unlabeled T-INGAP-PP at 5, 10 and 20 min, only 9% was at 60 min. Only liver, pancreas and small intestine specifically bound 125I-T-INGAP-PP. The pancreas tissue dose-response curve showed a 50% displacement at 39.102 ng/100 gbw, suggesting a low binding-affinity of its receptor. INGAP-mRNA was only identified in pancreatic islets and exocrine tissue. Our results suggest that INGAP transcription/expression is probably restricted to pancreas cells exerting its effect in a paracrine fashion. INGAP would be released and circulate bound to a serum protein from where it is bound and inactivated by the liver. Tissue binding could also explain INGAP´s immunocytochemical presence in small intestine, where it could affect epithelial cell turnover.