RESUMO
In order to determine which physiological functions can be regulated by the pancreatic CCKB/gastrin receptor, studies were carried out on pancreatic acini from mice expressing transgenic CCKB/gastrin receptors in the exocrine pancreas (ElasCCKB mice). Acini were stimulated by sulfated gastrin in the presence of SR 27897 (1.8 microM), blocking endogenous CCKA receptors. After 30 min incubation with gastrin, the secretion of chymotrypsinogen and amylase showed superimposable monophasic dose-response curves. Enzyme secretion was detectable and maximal at 100 pM and 1 nM of gastrin, respectively. No increase in chymotrypsinogen and amylase mRNAs was detected for doses of gastrin which specifically occupy the CCKB/gastrin receptor. In contrast, gastrin stimulated total protein synthesis in isolated acini from ElasCCKB mice. [35S]Methionine incorporation into total proteins was increased dose-dependently to a maximum for 30 pM gastrin and inhibited with higher doses (> 300 pM). Gastrin stimulated p70 S6 kinase activity for concentrations ranging from 10 pM to 1 nM. Gastrin-stimulated p70 S6 kinase activity and protein synthesis were blocked by rapamycin and wortmannin. Therefore, in ElasCCKB mice acinar cells, the CCKB/gastrin receptor mediates enzyme release and protein synthesis. However, a more efficient coupling of the CCKB/gastrin receptor to protein synthesis than to enzyme secretion was demonstrated. CCKB/gastrin receptor-stimulated protein synthesis likely results from an enhancement of mRNA translation and involves phosphatidyl inositol 3-kinase and p70 S6 kinase.
Assuntos
Pâncreas/metabolismo , Biossíntese de Proteínas , Receptores da Colecistocinina/metabolismo , Proteínas Quinases S6 Ribossômicas/metabolismo , Sequência de Aminoácidos , Amilases/genética , Amilases/metabolismo , Androstadienos/farmacologia , Animais , Quimotripsinogênio/genética , Quimotripsinogênio/metabolismo , Gastrinas/farmacologia , Humanos , Técnicas In Vitro , Camundongos , Camundongos Transgênicos , Dados de Sequência Molecular , Pâncreas/citologia , Pâncreas/efeitos dos fármacos , Peptídeos/genética , Fosfatidilinositol 3-Quinases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Receptor de Colecistocinina B , Receptores da Colecistocinina/efeitos dos fármacos , Receptores da Colecistocinina/genética , Sirolimo/farmacologia , WortmaninaRESUMO
This review summarizes recent advances on blood plasma patterns, receptors, secondary messengers and metabolism of gut regulatory peptides (i.e. gastrin, secretin, somatostatin, cholecystokinin, vasoactive intestinal polypeptide, pancreatic polypeptide, gastric inhibitory polypeptide, motilin), in young ruminants during fetal and perinatal stages, during the preruminant stage and at weaning. It also deals with their role in the digestive tract function and postabsorptive changes. Some pathological situations in young ruminants are considered. Recent molecular aspects of digestive enzyme synthesis are also reported.
