PMID- 9210176 OWN - NLM STAT- MEDLINE DCOM- 19970911 LR - 20190818 IS - 0196-9781 (Print) IS - 0196-9781 (Linking) VI - 18 IP - 4 DP - 1997 TI - Differential responsiveness of proximal and distal colonic mucosa to gastrin. PG - 559-65 AB - In vivo and in vitro experiments were performed to examine the responsiveness of the proximal and distal colonic mucosa to the growth-promoting action of gastrin. Infusion (osmotic minipump) of gastrin G-17-I (250 ng/kg/h) for 5 days to 4-month-old male Fischer-344 rats resulted in a significant (90-150%) increase in proliferative activity (as assessed by BrdU or PCNA immunoreactivity) in the distal colonic mucosa. In contrast, gastrin caused no apparent change in proliferative activity in the proximal colon. Because tyrosine kinases (Tyr-ks) are thought to be critically involved in regulating the trophic action of gastrin, responsiveness of isolated colonocytes from both segments of the colon to gastrin (1 x 10(-9) M) was also examined. Exposure of isolated colonocytes from the distal, but not from the proximal, colon to gastrin for 2 min resulted in a significant (73%) stimulation in Tyr-k activity. This was also accompanied by a marked rise in phosphorylation of at least six membrane proteins with M, of 55, 60, 70, 94, and 170 kDa. Tyr-k activity induced by gastrin in colonocytes from the distal colon was inhibited by tyrphostin (3.2 microM) but not by staurosporine (20 nM). In colonocytes from the distal colon, gastrin also stimulated phospholipase C (PLC) activity, which could also be inhibited by tyrphostin, but not by staurosporine. We conclude that mucosa of the distal, but not the proximal, colon responds to the trophic action of gastrin. Tyr-ks are thought to be involved in the regulation of this process. FAU - Malecka-Panas, E AU - Malecka-Panas E AD - VA Medical Center, Detroit, MI 48201, USA. FAU - Fligiel, S E AU - Fligiel SE FAU - Jaszewski, R AU - Jaszewski R FAU - Majumdar, A P AU - Majumdar AP LA - eng GR - AG 08438/AG/NIA NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Gastrins) SB - IM MH - Animals MH - Colon/cytology/*drug effects MH - Drug Evaluation, Preclinical MH - Gastrins/*pharmacology MH - Infusion Pumps, Implantable MH - Intestinal Mucosa/cytology/*drug effects MH - Male MH - Phosphorylation MH - Rats MH - Rats, Inbred F344 EDAT- 1997/01/01 00:00 MHDA- 1997/01/01 00:01 CRDT- 1997/01/01 00:00 PHST- 1997/01/01 00:00 [pubmed] PHST- 1997/01/01 00:01 [medline] PHST- 1997/01/01 00:00 [entrez] AID - S0196-9781(97)00061-2 [pii] AID - 10.1016/s0196-9781(97)00061-2 [doi] PST - ppublish SO - Peptides. 1997;18(4):559-65. doi: 10.1016/s0196-9781(97)00061-2.