Augmented inositol phosphate production in mesenteric arteries from diabetic rats

Worku Abebe, Kathleen M. MacLeod

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The effects of noradrenaline (NA) on contraction and phosphoinositide metabolism were compared in mesenteric arteries from rats with chronic streptozotocin-induced diabetes and from age-matched control rats. Maximum contractile responses of mesenteric arteries from diabetic rats to NA (30 μM) were significantly greater than control in both the presence and absence of extracellular Ca2+. Basal incorporation of [3H]myoinositol into total [3H]inositol phosphates was greater in diabetic than control mesenteric arteries. NA (30 μM) resulted in a time-dependent increase in total [3H]inositol phosphate production, which was also significantly greater in diabetic than in control preparations. The increase in total [3H]inositol phosphates produced by NA in both control and diabetic arterie was blocked by the α1-adrenoceptor antagonists, prazosin. Absolute levels of inositol 1,4,5-trisphosphate (I(1,4,5)P3), measured by protein binding assay, were also increased in response to 30 μM NA in both control and diabetic arteries. Although basal I(1,4,5)P3 levels were not significantly different, NA-induced increases in I(1,4,5)P3 were significantly greater in diabetic than in control arteries at each time-point measured. These data indicate that phosphoinositide metabolism is enhanced in mesenteric arteries from rats with chronic streptozotocin-induced diabetes in response to a maximum concentration of NA. Augmented production of the second messengers I(1,4,5)P3 and presumably, 1,2-diacylgylcerol may contribute to the enhanced maximum contractile responses of the diabetic arteries to NA.

Original languageEnglish (US)
Pages (from-to)29-36
Number of pages8
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume225
Issue number1
DOIs
StatePublished - Jan 14 1992
Externally publishedYes

Keywords

  • Contractile responses
  • Diabetes mellitus
  • Inositol 1,4,5-trisphosphate
  • Inositol phosphates
  • Mesenteric arteries
  • Noradrenaline

ASJC Scopus subject areas

  • Pharmacology

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