Biomedical subjects

Yasuyoshi Miki

Publications and source records attributed to Yasuyoshi Miki.

3 recordsLinked to original sources

PubMed2006

Different effects of optical isomers of the 5-HT1A receptor antagonist pyrapyridolol against postischemic guinea-pig myocardial dysfunction and apoptosis through the mitochondrial permeability transition pore.

The recovery (%) of the left ventricular developed pressure by (S)-(-)-pyrapyridolol (5 x 10(-8) M) (90.7%), an optical isomer of a new 5-HT1A receptor antagonist, was greater than that by (R)-(+)-pyrapyridolol (66.2%, control: 34.4%) against ischemia-reperfusion injury in perfused Langendorff guinea-pig hearts. In the perfused mitochondrial preparation, (S)-(-)-pyrapyridolol inhibited the mitochondrial Ca2+ (Cam) elevation that was brought about by the change of Ca2+ content or pH of perfusate, similar to findings with cyclosporin A, well known to be an inhibitor of the mitochondrial permeability transition pore (MPTP). The mitochondrial K(ATP) channel opener, diazoxide, also inhibited the Cam elevation, but the mitochondrial K(ATP) channel antagonist, 5-hydroxydecanoic acid, attenuated it. There were significantly fewer numbers of TUNEL-positive cells in these (S)-(-)-pyrapyridolol-treated hearts than the control or (R)-(+)-pyrapyridolol, with decreases of the caspase-3 activity. Therefore, these results suggest that (S)-(-)-pyrapyridolol likely inhibits the opening of the MPTP by preventing the Cam overload induced apoptosis related to endogenous 5-HT accumulation in ischemia-reperfusion hearts.

Adenosine Triphosphate↗

PubMed2005

Protective effects of sarpogrelate, a 5-HT2A antagonist, against postischemic myocardial dysfunction in guinea-pig hearts.

The protective effects of sarpogrelate (SG), a 5-HT2A antagonist, were investigated in perfused guinea-pig Langendorff hearts subjected to ischemia and reperfusion. Changes in cellular levels of high phosphorous energy, NO and Ca2+ in the heart together with simultaneous recordings of left ventricular developed pressure (LVDP) were monitored using an nitric oxide (NO) electrode, fluorometry and 31P-NMR. The recovery of LVDP from ischemia by reperfusion was 30.1% in the control, while the treatment with SG (5 x 10(-7) M) in pre- and post-ischemia hearts produced a gradual increase to 73.1 and 53.6%, respectively. At the final stage of ischemia, the intracellular concentration of Ca2+ ([Ca2+]i) and release of NO increased with no twitching and remained at a high steady level. The addition of SG increased the transient NO signal (TNO) level at the end of ischemia compared with the control, but [Ca2+]i during ischemia decreased. Meanwhile, mitochondrial Ca2+ uptake on acidification or Ca2+ content changes of the perfusate was suppressed by pre-treatment with SG or the KATP channel opener diazoxide, but not the KATP channel blocker 5-HD. The myocardial NO elevated with 5-HT in normal Langendorff hearts was suppressed by the treatment with SG. Therefore, the existence of the 5HT2A receptor in a Langendorff heart was anticipated. By in vitro EPR, SG was found to directly quench the hydroxy radical. Thus, these findings suggested that the 5-HT2A receptor induced in ischemia-reperfusion plays an important role in the mitochondrial KATP channel of hearts in close relation with NO and active oxygen radicals.

Animals↗

PubMed2004

Capturing of acidic macromolecules from biological samples using a temperature-responsive polymer modified with poly-l-lysine.

We synthesized a temperature-responsive polymer, N-(isopropylacrylamide)-methacrylic acid copolymer, to which poly-l-lysine was introduced. The synthesized polymer as well as the parent polymer showed reversible soluble-insoluble changes in response to temperature changes across the lower critical solution temperature at 32 degree C in an aqueous solution. We found that the polymer efficiently captured acidic bio-macromolecules such as RNA, glycosaminoglycans and mucin-type glycoproteins in biological samples, and the captured molecules were recovered using aqueous NaCl solutions at high concentration. The target acidic molecules thus obtained will be employed for further studies such as structural analysis after brief desalting procedure. The proposed method does not require any chromatographic separations, but only needs a small volume of an aqueous salt solution for releasing captured molecules. Overall procedures are quite easy and simple, and are completed at least within 1 h. We show a few examples for capturing RNA and glycosaminoglycans from cultured cells using the polymer.

Acrylamides↗