Abstract
Contraction of vascular smooth muscles is under the regulation of sympathetic activity and vasoactive hormones. It is known that release of Ca2+ from inositol 1,4,5-trisphosphate (IP3)-sensitive stores causes the initial phase of agonist-induced vasocontraction. In the present study, phenylephrine (PE)-induced contraction was measured in thoracic aortas isolated from the wild-type (WT) and IP3 receptor type 1 knockout (IP3R1-KO) mice, in order to specify the IP3 receptor subtype responsible for the agonist-induced contraction. PE (10−8–10−6 M)-induced aortic contraction in the IP3R1-KO mice was greatly diminished, compared to that in WT mice, and lacked the steep contraction which was invariably seen in WT aortas immediately after PE application at 10−6 M. But, high K+-induced contraction was indistinguishable between WT and IP3R1-KO aortas. Immunoblotting analysis demonstrated the presence of three IP3 receptor subtypes (IP3R1, IP3R2 and IP3R3) in WT mouse thoracic aorta; however, abundance of each subtype was in the order of IP3R1 > IP3R3 >> IP3R2. These results indicate that IP3R1 constitutes the Ca2+ release channels critical to vasocontraction regulated by sympathetic activity and vasoactive hormones. [J Physiol Sci. 2006;56 Suppl:S42]
