Folia Pharmacologica Japonica

Physiological and pharmacological actions of a neuroactive dipeptide, kyotorphin, and its precursor, L-arginine, and clinical application

Hiroshi TAKAGI

1990 Volume 96 Issue 3 Pages 85-96
Published: 1990
Released on J-STAGE: February 20, 2007

DOIhttps://doi.org/10.1254/fpj.96.3_85

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This review describes : 1. Recent findings about the physiological and pharmacological actions of kyotorphin that was isolated from the brain. 2. Biosynthesis, distribution, release, uptake, enzymatic destruction of this peptide in the body. 3. L-Arginine was found to be a precursor of kyotorphin. 4. Clinical application of the precursor to the treatment of chronic pain.

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Effects of lactulose on blood ammonia levels in beagles with end-to-side portacaval shunt

Yutaka MATSUOKA, Tsutomu URUNO, Makoto YAMADA, Akiko MIZUKAMI, Yuri KA ...

1990 Volume 96 Issue 3 Pages 97-101
Published: 1990
Released on J-STAGE: February 20, 2007

DOIhttps://doi.org/10.1254/fpj.96.3_97

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The effects of lactulose on blood ammonia and fecal pH in beagles with an end-to-side portacaval shunt were investigated. Concentrations of blood ammonia before and two weeks after the operation were 4.65 ± 0.34 cg/ml (N=12) and 8.66 ± 0.60 pg/ml (N=6), respectively (P<0.01), while there was no significant difference in fecal pH values before and after the operation. The blood ammonia concentrations in the control and lactulose-treated (2.1 g/kg, p.o.) groups after administration of meat were 12.65 ± 1.64 μg/ml (N =8) and 8.45 ± 0.90 μg/ml (N=8), respectively (P<0.05). The fecal pH values in the control and lactulose-treated (2.1 g/kg, p.o.) beagles were 6.24 ± 0.09 (N=8) and 5.58 ± 0.08 (N=8), respectively (P<0.01). The lowering effect of lactulose on the blood ammonia levels could not be ascribed to its laxative action alone, because the oral administration of lactulose at doses less than 2.1 g/kg induced no fluid evacuation. The present studies in the beagle suggest that the action of lactulose produce a lowering of fecal pH, causing an increase in the concentration of less absorbable ammonium ions and a decrease in the production of toxic nitrogenous compounds such as ammonia, resulting in a reduction in blood ammonia levels.

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Effects of autonomic nervous system-related agents on the intravesical pressure of the bladder in situ in female rats and ageing

Atsushi TOYOSHIMA, Sadayoshi ONODERA, Masaichi YOSHINAGA, Kunizou TAKE ...

1990 Volume 96 Issue 3 Pages 103-115
Published: 1990
Released on J-STAGE: February 20, 2007

DOIhttps://doi.org/10.1254/fpj.96.3_103

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We investigated cystometrically the effects of several autonomic nervous system-related agents on the intravesical pressure (IVP) in adult (11 ?? 23 weeks old, 200 ?? 350 g) and aged (2 years old, 350 ?? 770 g) female rats. Acetylcholine induced a dose-dependent and transient increase of IVP, which was competitively antagonized by pirenzepine weakly and by atropine strongly. These results suggest the predominancy of M-2 receptors. Adrenaline induced dual actions of decrease and increase of IVP at low and high doses, respectively. Adrenaline (at only high doses), noradrenaline and phenylephrine increased IVP but not clonidine, suggesting the predominancy of α-1 receptors. Isoproterenol, salbutamol and clenbuterol decreased IVP to same extent and the effect of isoproterenol was markedly antagonized by propranolol and slightly by atenolol, suggesting the predominancy of β-2 receptors. ATP increased IVP dosedependently but not adenosine, suggesting the predominancy of P-2 receptors. Serotonin and prostaglandin F_2α also increased IVP. In aged rats, the maximal response to acetylcholine was lower than in adult rats and the decrease in IVP by low doses of adrenaline was not observed. These results suggest that the increase of IVP involves the participation of cholinergic M-2 receptors to a large extent and also serotonergic, adrenergic α-1 and purinergic P-2 receptors to some extent and that the responsiveness to acetylcholine is reduced by ageing.

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Pharmacological properties of (±)-4-[2-hydroxy-3-(3-(2-methoxyphenoxy)-2-propylamino)propoxy]-1(2H)-isoquinolinone (N-1518), a new combined α- and β-adrenoceptor blocking drug

Toshiji SUGAI

1990 Volume 96 Issue 3 Pages 117-127
Published: 1990
Released on J-STAGE: February 20, 2007

DOIhttps://doi.org/10.1254/fpj.96.3_117

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The α, β-adrenergic blocking, antihypertensive and vasodilating properties of N-1518 were compared with those of labetalol. N-1518 blocked α- and β-adrenoceptors competitively as indicated by parallel rightward displacement of the dose-response curve of each agonist in isolated organs and in anesthetized dogs. As judged by pA₂ values and DR₁₀ values, N-1518 was as potent as labetalol in blocking α- and β-adrenoceptors. The β₁/α₁ ratio of N-1518 was 8.3 for pA₂ values in isolated organs and 13.6 for DR₁₀ values in anesthetized dogs, respectively. N-1518 inhibited dose-dependently the pressor response to intravenous administration of noradrenaline, but labetalol did not depress the response to noradrenaline in anesthetized dogs. N-1518 is composed of four optical isomers. The SR isomer was the most potent in blocking f3-receptors, and the RR-isomer was the most potent in blocking a-receptors. N-1518 has no intrinsic sympathomimetic activity in reserpinized rats and has no local anesthetic activity in guinea pigs. Single oral administration of N-1518 produced a fall in blood pressure in conscious SHR and renal hypertensive dogs without causing tachycardia. Intra-arterially administered N-1518 in the dog hindlimb resulted in vasodilation as indicated by the increase in blood flow. The magnitude of the responses was approximately 3 times more potent than that of labetalol.

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Antihypertensive effect of naftopidil (KT-611), a novel α₁-adrenoceptor antagonist, in freely moving experimental hypertensive rats and dogs

Hiromu KAWASAKI, Shigeru NAKAMURA, Koichiro TAKASAKI, Takahiro IWAMOTO ...

1990 Volume 96 Issue 3 Pages 129-139
Published: 1990
Released on J-STAGE: February 20, 2007

DOIhttps://doi.org/10.1254/fpj.96.3_129

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The antihypertensive effect of naftopidil (KT-611) following single oral administration was investigated in normotensive Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR), DOCA-Salt hypertensive rats (DHR), 2-kidney 1-clip renal hypertensive rats (RHR) and Grollman type renal hypertensive dogs with 1-kidney (RHD); and it was compared with that of the selective α₁-adrenoceptor antagonist prazosin. The blood pressure and heart rate were measured under the unanesthetized, unrestrained state through an arterial catheter that was chronically implanted into the abdominal aorta. In SHR and WKY, both KT-611 (10 and 30 mg/kg, p.o.) and prazosin (1 and 3 mg/kg, p.o.) markedly inhibited the pressor response to the α₁-adrenoceptor agonist phenylephrine (3 μg/kg, i.v.). KT-611 (10 to 100 mg/kg, p.o.) showed a dose-dependent hypotensive effect in SHR, DHR and RHR but not in WKY. The hypotensive effect of KT-611 reached maximum at 0.5 ?? 1 hr, lasted for 4 ?? 6 hr and was more potent in DHR and RHR than in SHR. The potency of KT-611 was 1/10 ?? 1/30 weaker than that of prazosin. In RHD, single oral administration of KT-611 (1 to 10 mg/kg) caused a dose-dependent and long-lasting hypotensive effect. These results suggest that KT-611 has a long-lasting hypotensive effect in experimental hypertensive animal models.

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[title in Japanese]

[in Japanese], [in Japanese], [in Japanese]

1990 Volume 96 Issue 3 Pages 141-143
Published: 1990
Released on J-STAGE: February 20, 2007

DOIhttps://doi.org/10.1254/fpj.96.3_141

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