Linked Life Data

9281310

Source:http://linkedlifedata.com/resource/pubmed/id/9281310

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-10-2
pubmed:abstractText
A number of early experiments suggested a relationship between methyl group metabolism and the exocrine secretion of the pancreas. These included nutritional studies showing that ethionine, the ethyl analog of methionine which inhibits cellular methylation reactions, is a specific pancreatic toxin. Other studies indicated that protein carboxymethylation might be involved. We now show that in vivo ethionine inhibits amylase secretion from freshly isolated rat pancreatic acini, while in vitro ethionine inhibits amylase secretion from the AR42J pancreatic cell line. S-Adenosylhomocysteine (SAH) is a product inhibitor of all methyltransferase reactions involving S-adenosylmethionine (SAM), and treatments that elevate cellular levels of SAH such as inhibition of S-adenosylhomocysteine hydrolase and the in vitro addition of adenosine and homocysteine result in the inhibition of amylase secretion in both isolated pancreatic acini and AR42J cells. Measurement of SAM and SAH levels in AR42J cells shows that inhibition of secretion is more closely related to elevation of SAH levels than to a decrease in the SAM/SAH ratio. Small G-proteins are carboxymethylated on the C-terminal prenylated cysteine and inhibitors of membrane-associated prenylcysteine methyltransferase, N-acetylfarnesylcysteine, N-acetylgeranylgeranylcysteine, and farnesylthioacetic acid (FTA), block secretion in AR42J cells. N-Acetylgeranylcysteine is not an inhibitor of the methyltransferase and does not inhibit amylase secretion. FTA inhibits membrane-associated prenylcysteine methyltransferase from AR42J cells with a Ki in the 45-69 microm range. These results suggest that a methylation event is needed for pancreatic exocrine secretion which may be the reversible methylation of a G-protein involved in signal transduction or membrane trafficking.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0003-9861
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
345
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
47-55
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Pancreatic exocrine secretion is blocked by inhibitors of methylation.
pubmed:affiliation
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.