Transcription, expression and tissue binding in vivo of INGAP and INGAP-related peptide in normal hamsters.
We studied islet neogenesis-associated protein (INGAP) transcription and its immunocytochemical presence in and binding in vivo of (125)I-tyrosylated INGAP pentadecapeptide ((125)I-T-INGAP-PP) to different normal male hamster tissues. (125)I-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 (125)I-T-INGAP-PP. The pancreas tissue dose-response curve showed a 50% displacement at 3.9x10(4) ng/100 g bw, 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.
Borelli
María I
MI
CENEXA, Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET, Centro Colaborador de la OPS/OMS), Facultad de Ciencias Médicas Universidad Nacional de La Plata, 60 y 120 (1900) La Plata, Argentina.
Del Zotto
Héctor
H
Flores
Luis E
LE
García
María E
ME
Boschero
Antonio C
AC
Gagliardino
Juan J
JJ
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D016207:Cytokines / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009928:Organ Specificity; D010179:Pancreas / Q000378:metabolism*; D000073718:Pancreatitis-Associated Proteins; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D012016:Reference Values; D014018:Tissue Distribution; D015533:Transcriptional Activation
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D016207:Cytokines; C500438:INGAP peptide; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D010446:Peptide Fragments; C000612141:REG3A protein, human; D012333:RNA, Messenger