Gastrin activates tyrosine kinase and phospholipase C in isolated rat colonocytes.
Postreceptor regulation of the trophic action of gastrin is not fully elucidated. Tyrosine kinase (Tyr-kinase) has been associated with receptors of a number of growth factors and plays an important role in regulation of cellular growth within the gastrointestinal tract. The aim of this study was to determine, whether Tyr-kinase plays a role in mediating the growth promoting action of gastrin and whether phospholipase C (PLC) is involved in the signal transduction pathway. Colonocytes isolated from Fischer 344 rats were incubated for 2 min with gastrin (10(-8) M) and assayed for Tyr-kinase and PLC activities. Incubations with gastrin resulted in 60%-70% rise in Tyr-kinase and 150%-200% rise in PLC activities over the corresponding basal levels. When processed separately, in proximal colon Tyr-kinase activation by gastrin was 15%-20%, while in distal colon 70%-80% as compared to the buffer control. Gastrin activation of both Tyr-kinase and PLC was abolished by Tyr-kinase inhibitor, tyrphostin-25 (3.2 microM) and was not affected by staurosporine (20 ng/ml). We conclude that Tyr-kinase is involved in the mechanism of trophic action of gastrin, and PLC activation appears to be the next step in the signal transduction pathway.
Małecka-Panas
E
E
Department of Digestive Tract Diseases and Metabolic Disorders, Medical School, Lódź, Poland.
Tureaud
J
J
Majumdar
A P
AP
D000818:Animals; D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation; D005755:Gastrins / Q000494:pharmacology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*
D005755:Gastrins; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases