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Diacylglycerol lipase and the contractile action of epidermal growth factor-urogastrone: evidence for distinct signal pathways in a single strip of gastric smooth muscle.

Authors
  • Yang, S G
  • Saifeddine, M
  • Chuang, M
  • Severson, D L
  • Hollenberg, M D
Type
Published Article
Journal
European Journal of Pharmacology
Publisher
Elsevier
Publication Date
Jul 12, 1991
Volume
207
Issue
3
Pages
225–230
Identifiers
PMID: 1909965
Source
Medline
License
Unknown

Abstract

In guinea pig gastric longitudinal muscle preparations, wherein epidermal growth factor-urogastrone (EGF-URO) causes contraction via the generation of arachidonate-derived prostaglandins, the specific diacylglycerol lipase (DG lipase) inhibitor, U57,908 (formerly designated RHC 80267) completely blocked EGF-URO and transforming growth factor-alpha (TGF-alpha)-mediated contraction, without affecting contractions caused by other agonists such as bradykinin, prostaglandin F2 alpha or arachidonic acid (AA). In contrast, the contractile actions of EGF-URO and TGF-alpha on the gastric circular muscle component, present in the same tissue strip as the longitudinal muscle preparation, were unaffected by concentrations of U57,908 that maximally inhibited contraction in the longitudinal muscle preparation. We conclude that in the longitudinal muscle preparation, EGF-URO acts not by the activation of phospholipase A2, but rather via the metabolism of diacylglycerol by DG lipase, thereby liberating arachidonic acid for the synthesis of contractile prostanoids. We also conclude that, even in the same tissue, the effects of EGF-URO on anatomically different components (longitudinal muscle versus circular muscle) can be mediated via two quite distinct signal transduction pathways.

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