Inositol 1,4,5-trisphosphate receptor subtypes are differentially distributed between smooth muscle and endothelial layers of rat arteries

Abstract

In blood vessels, the ability to control vascular tone depends on extracellular calcium entry and the release of calcium from inositol 1,4,5-trisphosphate receptor (IP 3R)-gated stores located in both the endothelial and smooth muscle cells of the vascular wall. Therefore, we examined mRNA expression and protein distribution of IP 3R subtypes in intact aorta, basilar and mesenteric arteries of the rat. IP 3R1 mRNA was predominantly expressed in all three arteries. Immunohistochemistry showed that IP 3R1 was present in both the muscle and endothelial cell layers, while IP 3R2 and IP 3R3 were largely restricted to the endothelium. Weak expression of IP 3R2 was observed in the smooth muscle of the basilar artery. Co-localisation studies of IP 3R subtypes with known cellular elements showed no association of any of the three subtypes with the endothelial cell plasma membrane, but a close association between the subtypes and actin filaments was observed in all cell layers. IP 3R2 was found to be present near the endothelial cell nucleus. We are the first to demonstrate differential IP 3R subtype distribution between the cell layers of the intact vascular wall and hypothesise that this may underlie the diversity of IP 3R-dependent responses, such as vasoconstriction, vasodilation and vasomotion, displayed by arteries.