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Role of inositol 1,4,5-trisphosphate receptors in vascular smooth muscle

This study has examined the expression and distribution of the type-1, type-2 and type-3 InsP<SUB>3</SUB>R subtypes in vascular smooth muscle in order to establish the roles of these subtypes. Immunoblotting of portal vein and aorta from neonatal (2-5 day old) and developed (6 week old) rat revealed comparatively greater expression of type-2 and type-3 InsP<SUB>3</SUB>R in the neonatal rat, compared to developed, and expression of type-1 InsP<SUB>3</SUB>R was decreased in neonatal rat compared to developed. In addition, there was a reorganisation of the internal calcium stores and altered intracellular InsP<SUB>3</SUB>R distribution observed between neonatal and developed rat. In permeabilised portal vein from developed rat, application of 100μM InsP<SUB>3</SUB> induced contractions of 54±7% of maximal activated contraction, whereas the permeabilised portal vein from neonatal rat, InsP<SUB>3</SUB> failed to induce contractility, indicating the type-1 InsP<SUB>3</SUB>R, but not type-2 and type-3 InsP<SUB>3</SUB>R subtypes are involved in excitation-contraction coupling. InsP<SUB>3</SUB>R subtype expression was also investigated in primary cultures of developed aortic cells. When seeded at subconfluent density these cells modulate to a "synthetic" phenotype believed to be similar to that found in vascular injury. InsP<SUB>3</SUB>R subtype expression is regulated during cell differentiation, and also in some vascular disease states. The type-2 and type-3 InsP<SUB>3</SUB>R subtypes may be involved in proliferating vascular smooth muscle, whereas the role of the type-1 InsP<SUB>3</SUB>R subtype is in excitation-contraction coupling in developed VSM. Therefore InsP<SUB>3</SUB>R expression may be a means of regulating the phenotypic properties of the vascular smooth muscle cell <I>in vivo</I>.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:367500
Date January 2001
CreatorsTasker, Paul N.
PublisherUniversity of Aberdeen
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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