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(Circulation Research. 1999;84:536-542.)
© 1999 American Heart Association, Inc.

Original Contribution

Expression and Distribution of the Type 1 and Type 3 Inositol 1,4,5-Trisphosphate Receptor in Developing Vascular Smooth Muscle

Paul N. Tasker, Francesco Michelangeli, Graeme F. Nixon

From the Department of Biomedical Sciences (P.N.T., G.F.N.), Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK, and the School of Biochemistry (F.M.), University of Birmingham, Birmingham, UK.

Correspondence to Graeme F. Nixon, PhD, Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. E-mail g.f.nixon{at}abdn.ac.uk

Abstract—The recent discoveries of inositol 1,4,5-trisphosphate (IP₃) receptor subtypes with different affinities for IP₃ and their potential involvement in development has important consequences for vascular smooth muscle. This study has examined the expression and distribution of the type 1 and type 3 IP₃ receptor subtypes in developing rat vascular smooth muscles. Immunoblotting of portal vein and aorta from neonatal (2 to 4 days) and fully developed (6 weeks) rats revealed significantly higher levels of the type 3 IP₃ receptor expression in neonatal, compared with developed, vascular smooth muscles. In contrast, expression of the type 1 IP₃ receptor in neonates was lower compared with developed vascular smooth muscles. Immunolocalization of the type 3 IP₃ receptors in neonatal tissues revealed that staining corresponded to the distribution of the sarcoplasmic reticulum (visualized by osmium ferricyanide staining of thin tissue sections), which suggested localization of the type 3 IP₃ receptor throughout the sarcoplasmic reticulum network. We conclude that type 3 IP₃ receptors are the predominant subtype in the development of vascular smooth muscle and are distributed throughout the sarcoplasmic reticulum in these cells. The switch in isoforms of the IP₃ receptor during development from the type 3 with low affinity for IP₃ to the higher-affinity type 1 receptor may play a role in calcium-mediated regulation of developing vascular smooth muscle.

Key Words: receptor • muscle, smooth, vascular • Ins(1,4,5)P₃ • development

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