Biomedical subjects

T Sasaguri

Publications and source records attributed to T Sasaguri.

58 records · Page 4Linked to original sources

PubMed1985

Mechanisms of vasodilation induced by vasoactive intestinal polypeptide in rabbit mesenteric artery.

Vasoactive intestinal polypeptide (VIP; over 10(-13) M) inhibited the norepinephrine (NE)-induced contraction evoked from the rabbit mesenteric artery. Increased concentrations of VIP (over 10(-9) M) inhibited the contractions induced by caffeine and 39 mM [K]o. However, VIP (below 10(-7) M) had no effect on the membrane potential and resistance of muscle cells. In Ca-free solution, VIP (10(-10) M) inhibited the NE-induced contraction, but the second application of NE after removal of VIP enlarged the amplitude of contraction over that in the control. Yet when 10(-9) M VIP was applied, both the first and second contractions were consistently smaller than those observed by application of 10(-10) M VIP. In Na- and Ca-free solution, repetitive applications of NE generated contractions longer than those observed in Ca-free solution. When VIP (10(-10) M) was applied once (3 min), the contraction was inhibited only once during repetitive applications of NE. VIP (over 10(-9) M) dose dependently inhibited the NE-induced contraction and had a long-lasting inhibition after washout of the tissue. In saponin-treated skinned muscles, VIP (10(-7) M) had no effect on the Ca-induced contraction or on the Ca store sites. VIP (over 10(-8) M) was about 10 times more potent than equimolar concentrations of isoproterenol in increasing the content of adenosine 3', 5'-cyclic monophosphate (cAMP). These results indicate that VIP (10(-10) M) selectively inhibits the Ca release activated by NE, and high concentrations (over 10(-9) M) would expectedly increase the Ca extrusion from cells following increase in the levels of cAMP.

Animals↗

PubMedDate not supplied

Irreversible inhibition of Ca2+ release in saponin-treated macrophages by the photoaffinity derivative of inositol-1, 4, 5-trisphosphate.

D-myo-inositol-1,4,5-trisphosphate (InsP3) is a putative intracellular second messenger for the mobilization of Ca2+ from intracellular stores, in particular, the endoplasmic reticulum. Specific binding sites on the endoplasmic reticulum may participate in the InsP3-induced release of Ca2+ from the Ca2+ pool. To examine the specific binding sites on the endoplasmic reticulum, we synthesized an arylazide derivative of InsP3 for photoaffinity labelling; InsP3 coupled to p-azidobenzoic acid (InsP3-pAB) using N,N'-carbonyldiimidazole (CDI) was obtained at a 9-11% yield. Here, we report that InsP3-pAB, but not an arylazide derivative of inositol-1,4-bisphophate (Ins(1,4)P2), causes the irreversible inhibition of InsP3-induced release of Ca2+ in saponin-permeabilized photo-irradiated macrophages. The irreversible inhibition by InsP3-pAB after photo-irradiation was prevented by a 10-fold excess of unmodified InsP3.

Affinity Labels↗

PubMedDate not supplied

Differentiation-inducing factor-1, a morphogen of dictyostelium, induces G(1) arrest and differentiation of vascular smooth muscle cells.

Differentiation-inducing factor-1 (DIF-1) is a morphogen that induces differentiation of DICTYOSTELIUM: Recently, DIF-1 has been shown to inhibit proliferation and induce differentiation in tumor cells, although the underlying mechanisms remain unknown. In this study, we examined the effects of DIF-1 on the proliferation and differentiation of vascular smooth muscle cells, to explore novel therapeutic strategies for atherosclerosis. DIF-1 nearly completely inhibited DNA synthesis and cell division in mitogen-stimulated cells. DIF-1 inhibited the phosphorylation of the retinoblastoma protein and the activities of cyclin-dependent kinase (Cdk) 4, Cdk6, and Cdk2, which phosphorylate the retinoblastoma protein. DIF-1 strongly suppressed the expression of cyclins D1, D2, and D3, as well as those of cyclins E and A, which normally began after that of the D-type cyclins. The mRNAs for the smooth muscle myosin heavy chains SM1 and SM2 were expressed in quiescent cells in primary culture, and these expression levels decreased after mitogenic stimulation. In the presence of DIF-1, the rate of the reduction was significantly decelerated. Moreover, the addition of DIF-1 to dedifferentiated cells induced the expressions of SM1 and SM2, accompanied by a reduction in the level of SMemb, a nonmuscle-type myosin heavy chain. Therefore, DIF-1 seemed to interrupt a very early stage of G(1) probably by suppressing the expressions of the D-type cyclins. Furthermore, this compound may prevent phenotypic modulation and induce differentiation of vascular smooth muscle cells.

Cell Differentiation↗

PubMedDate not supplied

Systemic necrotizing vasculitis with renal involvement accompanied by remarkable eosinophilia: a case with overlapping features of polyarteritis nodosa and allergic granulomatous angiitis.

A 71-year-old woman was clinically suspected of allergic granulomatous angiitis (AGA) because of preceding allergic diseases including bronchial asthma, remarkable eosinophilia (14,300/mm3), mononeuritis multiplex, positive rheumatoid factor, elevated serum immunoglobulin E, and eosinophilic inflammation of the kidney. Autopsy findings, however, were characterized of polyarteritis nodosa (PAN). Necrotizing angiitis was present in several organs except for the lung; focal and segmental glomerular lesions with crescent formation were observed in the kidney, and granuloma formation was not found. This case may be an intermediate type between PAN and AGA (an overlap syndrome) and provide useful information on the clinical entities of systemic necrotizing vasculitis.

Aged↗