Regulation of pancreatic tyrosine kinase and phosphatase activities by cholecystokinin and somatostatin.
Phosphorylation and dephosphorylation of proteins on tyrosyl residues are important reactions involved in cellular activities, namely, those associated with growth and differentiation. Although it is accepted that cholecystokinin (CCK) and somatostatin (SS) stimulate and inhibit pancreatic growth and secretion, the cellular mechanisms by which these two hormones trigger their stimulatory and inhibitory effects are not well known. It has recently been suggested that, in acinar cells, one of the early signals of SS would involve activation of a membrane tyrosine phosphatase, whereas the signal associated with CCK may involve stimulation of protein tyrosine phosphorylation. This study examines the effects of caerulein (Cae) and SMS-201-995 (SMS) on pancreatic growth, particulate and crude cytosolic tyrosine kinase (TRK), and phosphotyrosine phosphatase (PTase) activities. Rats infused intravenously with 0.05% bovine serum albumin (control), Cae (0.25 micrograms.kg-1.h-1), or SMS (5 micrograms.kg-1.h-1) were killed after 0.5, 1, 2, 3, 4, 8, 12, 24, and 48 h of infusion. The pancreas was excised, weighed, and evaluated for contents of DNA and protein and for TRK and PTase activities. The effects of subtotal pancreatectomy on TRK and PTase activities were also examined after 1, 2, 3, 4, and 7 days. In response to Cae, pancreatic growth was evident after 48 h and was accompanied by sustained increases in particulate TRK and particulate PTase. Increases in membrane PTase activities were localized on membranes of the zymogen granules. SMS treatment was associated with increases in pancreatic weight and protein as a result of inhibition of secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Rivard
N
N
Department of Biology, Faculty of Science, University of Sherbrooke, Quebec, Canada.
Lebel
D
D
Lainé
J
J
Morisset
J
J
D000818:Animals; D002108:Ceruletide / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D008297:Male; D015282:Octreotide / Q000494:pharmacology; D010179:Pancreas / Q000201:enzymology*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000494:pharmacology*
D013004:Somatostatin; D002108:Ceruletide; D002766:Cholecystokinin; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D015282:Octreotide