Ken Nagashima

Inhibition of nerve growth factor-induced neurite outgrowth of PC12 cells by a protein kinase inhibitor which does not permeate the cell membrane

K‐252a, a protein kinase inhibitor of microbial origin, has proven to be a specific inhibitor of nerve growth factor. In this study, the effects of K‐252b, the 9‐carboxylic acid derivative of K‐252a, on nerve growth factor‐induced neurite outgrowth in PC12 cells was examined. K‐252b is hydrophilic and does not permeate the cell membrane of PC12 cells, whereas K‐252a clearly does. K‐252b is, however, as potent as K‐252a itself in inhibiting the nerve growth factor‐induced neurite outgrowth. These results can be interpreted to suggest that effects of K‐252b may be through surface‐bound/anchored K‐252b‐sensitive molecules on PC12 cells.

Protective effects of benidipine on hydrogen peroxide-induced injury in rat isolated hearts.

We investigated the effects of benidipine (hydrochloride), a calcium antagonist, on hydrogen peroxide (H2O2)‐induced injury in Langendorff‐perfused rat hearts. The hearts were aerobically perfused at a constant flow and exposed to H2O2 (600 μmol L−1) for 4 min, resulting in the oxidative stress‐induced myocardial dysfunction (e.g., decrease in the left ventricular developed pressure) and myocardial cell injury (e.g., increase in the release of lactate dehydrogenase). Pretreatment of the hearts with benidipine or nifedipine was performed for 20 min until the start of H2O2 exposure. Benidipine at 1 nmol L−1 and nifedipine at 10 nmol L−1 decreased the myocardial contractility and perfusion pressure to a similar degree in the hearts under normal conditions. Benidipine (1 nmol L−1) significantly reduced the H2O2‐induced myocardial damage. Nifedipine (10 nmol L−1) also tended to exhibit similar effects. Benidipine inhibited the increase in tissue lipid peroxidation induced by H2O2. The results suggest that, in addition to the calcium antagonism, benidipine possesses other actions responsible for the cardioprotective effects, to which the antioxidant activity of benidipine may partly contribute.

Benidipine Inhibits Apoptosis During Ischaemic Acute Renal Failure in Rats

We have investigated the effects of benidipine (hydrochloride), a calcium antagonist, against ischaemic acute renal failure in rats. Using histological examination, we studied whether the inhibition of apoptosis was associated with the protective effects of benidipine on the ischaemic renal injury.