Phosphoinositide-derived second messengers and the regulation of Ca2+ in vascular smooth muscle

S. R. Nahorski, R. A. Wilcox, J. J. Mackrill, R. A.J. Challiss

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Vascular smooth muscle and the phosphoinositide signalling pathway: Vascular smooth muscle tone can be regulated by an array of agonists which act via receptor-mediated transmembrane signalling pathways to modify the concentrations of key intracellular second messengers. Following agonist stimulation the phosphoinositide signalling pathway initiates the contraction process in vascular smooth muscle, via the second messengers myo-inositol 1,4,5-trisphosphate and sn-1,2-diacylglycerol. Diversity of calcium-regulatory mechanisms: The vascular smooth muscle cell apparently sustains the contraction with a number of diverse mechanisms, which act to increase intracellular Ca2+ by regulating both Ca2+ influx across the plasma membrane and Ca2+ release from intracellular calcium stores, or may act in the apparent absence of elevated cytosolic Ca2+ concentrations. Future research: The exact nature of these physiological interactions and their exact function are not yet fully understood. In particular, identification of the natural role of specific phospholipase C(δ), phospholipase C(γ) and protein kinase C isozymes and also the various ryanodine and myo-inositol 1,4,5-trisphosphate receptor subtypes present in vascular smooth muscle will prove critical to future understanding of the regulation of vascular smooth muscle tone in both the normal and the hypertensive phenotype.

Original languageEnglish
Pages (from-to)S133-S143
JournalJournal of Hypertension, Supplement
Volume12
Issue number10
Publication statusPublished - Dec 1994
Externally publishedYes

Keywords

  • Calcium mobilization
  • Endothelial cells
  • Inositol 1,4,5-trisphosphate
  • Inositol 1,4,5-trisphosphate receptors
  • Phosphatidylinositol 4,5-bisphosphate
  • Ryanodine receptors
  • Vascular smooth muscle

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