Chronic ethanol consumption induces gene expression of pancreatic monitor peptide, but not SPINK1/PSTI-56, in rats.
The primary factors that predispose humans to the development of alcoholic pancreatitis are unknown. One of the earliest observations in humans in whom this disease develops is pancreatic hypersecretion caused by unknown mechanisms. Messenger RNA (mRNA) differential display was performed in a rat model to investigate the molecular mechanisms associated with ethanol-induced pancreatic hypersecretion. Male Wistar rats were pair-fed Lieber-DeCarli diets with or without ethanol for 7 days or 4 weeks. Total RNA was extracted from the pancreas and its neurohormonal control sites. Differentially expressed complementary DNA (cDNA) tags were isolated, cloned, and sequenced. One 248-bp cDNA was consistently and strongly induced in the pancreata of rats fed ethanol for 4 weeks. The sequence was highly homologous to both rat pancreatic monitor peptide (MP) and pancreatic secretory trypsin inhibitor (PSTI-56), also known as serine protease inhibitor, Kazal type 1 (SPINK1). Confirmatory reverse-transcription-polymerase chain reaction showed that PSTI-56 expression remained unchanged, whereas MP mRNA levels were elevated more than four times in the pancreata of ethanol-fed rats. These results indicate that long-term ethanol ingestion increases MP mRNA levels in the rat pancreas. Because MP stimulates cholecystokinin release and cholecystokinin is an important stimulant of pancreatic secretion, the enhanced MP gene expression may contribute to pancreatic hypersecretion.
Li
H S
HS
Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15216, USA.
Deng
X Y
XY
Thompson
B S
BS
Zhang
J Y
JY
Wood
P G
PG
Eagon
P K
PK
Whitcomb
D C
DC
D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D015870:Gene Expression; D020869:Gene Expression Profiling; D006133:Growth Substances / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics*
D018076:DNA, Complementary; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C504705:Spink1 protein, rat; D014359:Trypsin Inhibitor, Kazal Pancreatic