Characterization of cyclic 3', 5'-nucleotide phosphodiesterase activity in an islet cell tumor of the syrian hamster

Ulrich K. Schubart, Linda Udem, Stephen G. Baum, Ora M. Rosen

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

During the purification of cyclic nucleotide phosphodiesterase (diesterase) activity from an insulin-secreting islet cell tumor of the syrian hamster, two soluble diesterases (diesterase I and diesterase II) and a particulate diesterase were resolved. Based on gel filtration, the estimated molecular weights of diesterases I and II were approximately 180,000. All of the diesterases had 'low' (approximately 1 μM) and 'high' (10-20 μM) KM's for both cAMP and cGMP. A heat-stable protein activator was partially separated from the soluble diesterases upon DEAE-cellulose chromatography. The activator enhanced the activity of the soluble diesterase 2 1 2-fold at cyclic nucleotide concentrations of 5 μM. No stimulation of diesterase activity was observed at higher (50-500 uM) substrate concentrations. The following compounds (in order of decreasing potency) inhibited both the soluble and particulate diesterases: papaverine, SQ 20009, xanthine derivatives, diphenylhydantoin, diazoxide, sulfonylureas, nicotinamide and catecholamines. Insulin, proinsulin, prostaglandins E1 and F, secretin, glucagon, colchicine, glucose, streptozotocin and imidazole were all without effect. Sulfhydryl-containing compounds and a number of amino acids enhanced the activity of soluble and paniculate diesterases. These investigations coupled with studies of adenylate cyclase and protein kinase activities, intracellular cyclic nucleotide levels and insulin secretion will provide a basis for understanding the role of cAMP in insulin secretion.

Original languageEnglish (US)
Pages (from-to)227-247
Number of pages21
JournalMolecular and Cellular Endocrinology
Volume1
Issue number3
DOIs
StatePublished - Jun 1974

Keywords

  • cAMP
  • insulin secreting tumor
  • insulin secretion
  • islet cell tumor
  • phosphodiesterase
  • phosphodiesterase activator

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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