Predominant role of type 1 IP3 receptor in aortic vascular muscle contraction.

ABSTRACT

Inositol 1,4,5-trisphosphate receptor (IP(3)R) plays a crucial role in generating Ca(2+) signaling and three subtypes of IP(3)R have been identified. In spite of a high degree of similarity among these subtypes, their effects on spatio-temporal Ca(2+) patterns are specific and diverse; therefore the physiological significance of the differential expression levels of IP(3)R subtypes in various tissues remains unknown. Here, we examined the relative contribution of the specific subtype of IP(3)Rs to the agonist-induced Ca(2+) signaling and contraction in IP(3)R-deficient vascular smooth muscle cells and found that IP(3)R1 deficient cells exclusively showed less sensitivity to the agonist, compared to those from the other genotypes. We also found that IP(3)R1 dominantly expressed in vascular aortae on a consistent basis, and that phenylephrine (PE)-induced aortic muscle contraction was reduced specifically in IP(3)R1-deficient aortae. Taken together, we concluded that IP(3)R1 plays a predominant role in the function of the vascular smooth muscle in vivo.