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Akemichi Baba

Publications and source records attributed to Akemichi Baba.

75 records · Page 5Linked to original sources

The nitric oxide donor NOC12 protects cultured astrocytes against apoptosis via a cGMP-dependent mechanism.

We examined the effect of 3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene (NOC12), a nitric oxide (NO) donor, on apoptosis in cultured astrocytes. Reperfusion after hydrogen peroxide (H2O2) exposure caused a decrease in cell viability, loss of mitochondrial membrane potential, caspase-3 activation, DNA ladder formation, and nuclear condensation. NOC12 at 10-100 microM significantly attenuated these apoptotic changes, while the NO donor at 1 mM caused cell injury and exacerbated the H202-induced cell injury. NOC12 increased intracellular cGMP levels in a dose dependent manner with the maximal effect at 100 microM. The protective effect of NOC12 was mimicked by the NO-independent guanylate cyclase activator 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole, and was attenuated by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and the cGMP-dependent protein kinase inhibitor KT5823. ODQ and KT5823 did not block but rather exacerbated the cytotoxic effect of NOC12 at 1 mM. These findings demonstrate that lower concentrations of NOC12 inhibit the H2O2-induced apoptosis of astrocytes in a cGMP-dependent way, but higher concentrations of NOC12 show a toxic effect on astrocytes in a cGMP-independent way.

Animals↗

Modulation by 5-hT2A receptors of aggressive behavior in isolated mice.

The present study examines whether isolation-rearing affects sensitivity of 5-hydroxytryptamine (5-HT)2A receptors and the functional interaction between 5-HTIA and 5-HT2A receptors in mice. The 5-HT2A-receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI)-induced head twitch response was significantly greater in isolated mice than in grouped mice. DOI increased isolation-induced aggressive behavior, and the 5-HT2A-receptor antagonist ritanserin decreased it. The 5-HTIA-receptor agonist (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole HCl (MKC-242) inhibited the DOI-enhanced aggressive behavior. MKC-242 inhibited DOI-induced head twitch response. These findings suggest that 5-HT2A receptors play a role in aggressive behavior in isolated mice and imply that the antiaggressive effect of MKC-242 may be mediated partly by the inhibition of 5-HT2A-receptor function.

Aggression↗

PAC1 receptor-mediated relaxation of longitudinal muscle of the mouse proximal colon.

Since pituitary adenylate cyclase-activating polypeptide (PACAP) was shown to partially mediate nonadrenergic, noncholinergic (NANC) relaxation of longitudinal muscle of the proximal colon of ICR mice, we further studied the receptor subtype activated by PACAP by using a mutant mouse whose PAC1 receptors are markedly reduced. In wild-type mice, the PACAP-mediated component of NANC relaxation was 33%, but it was absent in the mutant mice. The potency of exogenous PACAP in inducing relaxation in the mutant mice was one hundredth of that in wild-type mice. VPAC1 and VPAC2 receptors were not suggested to have any role in the relaxation. These results suggest that PACAP mediates NANC relaxation of longitudinal muscle of mouse proximal colon via PAC1 receptors.

Animals↗