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Volume 93 (1989)
- Issue 6 Pages 315-
- Issue 5 Pages 271-
- Issue 4 Pages 203-
- Issue 3 Pages 89-
- Issue 2 Pages 29-
- Issue 1 Pages 7-
Volume 93, Issue 4
Displaying 1-7 of 7 articles from this issue
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Hiroshi HIGUCHI1989 Volume 93 Issue 4 Pages 203-218
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSNeuropeptide Y (NPY) is widely distributed in the central and sympathetic nervous systems and has a variety of central actions including regulation of blood pressure and peripheral actions; e.g., continuous vasoconstriction and inhibition of catecholamine release. The NPY receptor can be divided into 2 subclasses (Y1, Y2), and these subclasses are coupled to GTP binding proteins (Gi, Go, Gp ...... ) . Recently, human and rat prepro-NPY mRNA and NPY gene structures have been determined by cDNA and genomic cloning and sequencing. The strong evolutionary conservation of these structures suggested that NPY is an essential peptidergic neurotransmitter. Little is known about the biosynthesis, processing, degradation of NPY and NPY gene expression. We showed that NPY gene expression and NPY biosynthesis are regulated by neural activity, hormone, and intracellular second messengers via neurotransmitter receptors. The change of NPY gene expression by these neural factors is considered to be a good model for a synaptic plasticity, because these changes cause the changes of synaptic transmission. Furthermore, because NPY is expressed in sympathetic neurons and its gene expression increased markedly on the differentiation of adrenergic cells, this study about NPY gene expression could provide good clues for elucidating the differentiation of sympathetic neurons.View full abstractDownload PDF (12129K) -
Yoshitaka INO, Minoru ODA, Takuo SATO, Masahiro IWAKI1989 Volume 93 Issue 4 Pages 219-224
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSN-α-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline (MK-0521) is a new non-sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor. The present investigation describes its ACE and other enzymes inhibitory properties and compares it to those of captopril, MK-421 and MK-422 in vitro. MK-0521 inhibited rat pulmonary ACE by 50% (IC50) at a concentration of 3nM and was 6.13 times more potent than captopril. The IC50 values of MK-421 and MK-422 against ACE were 2, 000 nM and 3.5 nM, respectively. MK-0521 had practically no inhibitory activities against carboxypeptidase A, carboxypeptidase B, leucineaminopeptidase, papain, pepsin and trypsin. The kinetic study on the inhibitory activity of M-0521 against ACE using Lineweaver-Burk plots indicated that MK-0521 exerted competitive ACE inhibition. The dialysis study conducted on the ACEMK-0521 complex revealed that the inhibitory effect of MK-0521 against ACE was reversible. In the guinea pig ileum, MK-0521 potentiated the contractile effect of bradykinin and depressed the contractile effect of angiotensin I. These effects on bradykinin and angiotensin I were 33.11 and 2.63 times more potent than that of captopril, respectively. The present results suggest that MK-0521 may show a potent hypotensive effect in vivo.View full abstractDownload PDF (4713K) -
Minoru ODA, Yoshitaka INO, Kunihiko SUZUKI, Takuo SATO, Satomi IWAMOTO ...1989 Volume 93 Issue 4 Pages 225-234
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSAngiotensin converting enzyme (ACE) inhibitory activity of MK-0521 in dogs and the effects of its single oral administration on blood pressure and the renin-angiotensin system in 2-kidney Goldblatt hypertensive dogs were compared with those of captopril and MK-421. MK-0521 at 0.001 ?? 0.1 mg/kg, i.v., or 0.01 ?? 1 mg/kg, p.o., attenuated the pressor effect of angiotensin I without affecting that of angiotensin II and augmented the depressor effect of bradykinin. The potency of MK-0521 to reduce the pressor effect of angiotensin I was 9.8 times that of captopril by intravenous administration, and by oral administration, it was 15.9 ?? 32.1 times that of captopril and approximately 3 times that of MK-421. When administered orally, the onset of action and the time to peak effectiveness were more rapid than those of MK-421, but slower than those of captopril. Duration of the action of MK-0521 was longer than that of captopril and equal or longer than that of MK-421. The inhibition of ACE was well correlated with serum MK-0521 levels. MK-0521 produced a dose-dependent antihypertensive effect in 2-kidney Goldblatt hypertensive dogs at over 0.3 mg/kg, p.o., without affecting the heart rate. The antihypertensive effect of MK-0521 was persistent and approximately 3 times more potent than that of captopril. MK-0521 inhibited the serum ACE activity and increased the plasma renin activity, while it had a tendency to decrease plasma aldosterone level. These changes were parallel to the time course of the antihypertensive effect. These results suggest that the main mechanism of the antihypertensive effect of MK-0521 is the suppression of angiotensin II production due to the inhibition of the ACE.View full abstractDownload PDF (7194K) -
Minoru ODA, Kunihiko SUZUKI, Yoshitaka INO, Takuo SATO, Masahiro IWAKI1989 Volume 93 Issue 4 Pages 235-243
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSMK-0521 and captopril were orally administered to acute (6 to 8 days after unilateral renal artery constriction) and chronic (2 to 2.5 months after the constriction) 2-kidney Goldblatt hypertensive dogs for 7 to 21 days. MK-0521 lowered the blood pressure to similar extents in the acute and chronic stages of hypertension. The antihypertensive effect of MK-0521 was dose-dependent and persistent even after its cessation. Captopril also produced an antihypertensive effect, although the effect in the chronic stage of hypertension was less prominent than that in the acute stage of hypertension. MK-0521 was more inhibitory on the renin-angiotensin system than captopril. In the acute stage of hypertension, the dogs treated with MK-0521 had increased angiotensin converting enzyme (ACE) activity, while they had decreased plasma angiotensin II level and elevated plasma angiotensin I level and plasma renin activity. These results clarified the inhibitory effect of MK-0521 on ACE. In contrast, in the chronic stage of hypertension, MK-0521 showed no depression of plasma angiotensin II. There were no significant changes in daily urinary volume, and renal clearances of sodium, potassium and creatinine. These results suggest that the major mechanism of the antihypertensive effect of MK-0521 in 2-kidney Goldblatt hypertensive dogs is an inhibition of the ACE. In addition, the different effects in the acute and chronic hypertensive dogs suggest that some differences exist in the mechanisms of maintaining blood pressure between the two stages of 2-kidney Goldblatt hypertensive dogs.View full abstractDownload PDF (6262K) -
Hisashi KURIBARA, Sakutaro TADOKORO1989 Volume 93 Issue 4 Pages 245-253
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSSingle administration of NC-1100 (3, 10 or 30 mg/kg, p.o.) produced no marked change in the ambulatory activity and discrete lever-press avoidance response. However, 100 mg/kg of this drug produced a toxic effect which was characterized by salivation, tremor, clonic convulsion, etc., but none of the mice died. NC-1100 enhanced the ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) at 3 and 10 mg/kg, while it failed to modify that of scopolamine (0.5 mg/kg, s.c.). NC-1100, at 100 mg/kg, suppressed both the established discrete lever-press and shuttle avoidance responses, probably due to non-specific and toxic effects. When NC-1100 at 10 mg/kg was administered, the response rate increased only in the shuttle avoidance situation in which the avoidance established mice were used. Furthermore, when NC-1100 at 30 mg/kg was administered immediately before the start of the training session, the avoidance rate increased. However, there was no marked change in the avoidance rate in the 2nd training session which was conducted 24 hr after the 1st training session without the drug administration. Additionally, the response rate increased in the 1st and 2nd training sessions after 10 and 30 mg/kg of NC-1100. The present results suggest that NC-1100 may show a behavior-facilitating effect, although its effect is mild and different from that of typical central stimulants such as methamphetamine.View full abstractDownload PDF (6034K) -
Kazuhiro GOTO, Mamoru SUEKAWA, Eikichi HOSOYA1989 Volume 93 Issue 4 Pages 255-260
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSIt has been demonstrated that TJ-8007 (Tsumura-Zokumeito, A traditional Chinese medicine) has a protective effect against cerebral anoxia. This study was done to elucidate the protective mechanism of TJ-8007 against cerebral ischemia and anoxia. TJ-8007 (0.3 ?? 3.0g/kg, p.o.) inhibited the rise in the cumulative mortality rate after ligation of the bilateral carotid artery (BCA) in mice. TJ-8007 also significantly prolonged the survival time at the dose of 3.0 g/kg, p.o. However, TJ-8007 (1.0 or 3.0 g/kg, p.o.) did not affect the mean survival time after ligation of BCA in Mongolian gerbils and the gasping movement in a decapitated mouse head that served as a complete ischemic model. Ifenprodil (30 mg/kg, p.o.) also showed the protective effect only against ischemic death after ligation of BCA in mice. TJ-8007 (1.0 or 3.0 g/kg, p.o.) increased the vertebral blood flow, but showed no effect on the internal carotid blood flow in anesthetized dogs. These results suggest that the mechanism for the cerebral protective effect of TJ-8007 may be due to its ameliorating action on the cerebral circulation.View full abstractDownload PDF (3960K) -
Shin-ichi MORISHITA, Takashi SAITO, Masamichi SHOJI, Akira TANAKA, Kum ...1989 Volume 93 Issue 4 Pages 261-270
Published: 1989
Released on J-STAGE: February 20, 2007
JOURNAL FREE ACCESSPharmacological effects of Reiousan, a crude drug preparation consisting of bezoar and ginseng, on experimental hepatic injuries and hepatic functions were studied. After administration of Reiousan, carbon tetrachloride, d-galactosamine and α-naphthylisothiocyanateinduced experimental hepatic injuries in rats were inhibited. Facilitation of recovery from increased retention rate of sulfobromophthalein in hepatectomized rats, increase in hepatic blood flow, inhibition of superoxide anions, and decrease in blood ethanol concentration in rats administered ethanol were observed after application of Reiousan. Inhibitory effects of Reiousan on experimental hepatic injuries may result from the increase in hepatic blood flow and inhibition of superoxide anions.View full abstractDownload PDF (9838K)
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