Biomedical subjects

Y Kasuya

Publications and source records attributed to Y Kasuya.

At least 145 records · Page 8Linked to original sources

PubMed1993

The effect of chronic treatment with naltrindole, a selective delta-opioid antagonist, on mu-opioid receptor-mediated antinociception in diabetic mice.

The effects of chronic treatment with naltrindole (NTI), a selective delta-opioid receptor antagonist, on the antinociceptive effects of mu-opioid agonists, such as morphine and [D-Ala2, N-MePhe4, Gly-ol(5)]enkephalin (DAMGO) were examined in diabetic mice. Antinociception induced by morphine (10 micrograms, ICV) and DAMGO (0.5 microgram, ICV) was significantly lower in diabetic mice than in non-diabetic mice. The low sensitivities to the antinociceptive potencies of ICV morphine (10 micrograms) and DAMGO (0.5 micrograms) in diabetic mice were reversed compared with those in saline-treated non-diabetic mice when diabetic mice had been pretreated with NTI (2 mg/kg per day, SC) for 14 days. Naive mice which had been injected with spleen mononuclear cells from saline-treated diabetic mice were less sensitive to DAMGO-induced antinociception. However, adoptive transfer of spleen mononuclear cells from NTI-treated diabetic mice to naive mice had no effect on the recipients' antinociceptive sensitivity to DAMGO. These results suggest that the effect of NTI on the sensitivity to mu-opioid agonists in diabetic mice may be due to the immunosuppressive effects of NTI.

Analgesics↗

PubMed1993

Cold water swim stress inhibits the nociceptive responses to intrathecally administered somatostatin, but not substance P.

The effects of cold water swim stress (CWSS) on the nociceptive responses to i.t. administered substance P (SP) and somatostatin (SST) were examined. Male ICR mice, weighing about 30 g, were forced to swim in water at 20 degrees C for 3 min. In unstressed mice, i.t. injection of SP (0.1 nmol) and SST (1 nmol), respectively, produced nociceptive-related behaviors. Although CWSS had no effect on the intensity of the SP-induced nociceptive responses, CWSS significantly reduced the intensity of the SST-induced nociceptive responses. The effect of CWSS on the SST-induced nociceptive responses was blocked by naloxone (5 mg/kg, s.c.) and naltrindole (1 mg/kg, s.c.), a selective delta-opioid receptor antagonist, but not by beta-funaltrexamine (20 mg/kg, s.c.), a selective mu-opioid receptor antagonist. These results indicate that CWSS may selectively reduce the SST-induced nociceptive responses primarily through delta-opioid receptors.

Animals↗

PubMed1993

Nociceptive responses to intrathecally administered substance P and somatostatin in diabetic mice.

Male ICR mice were rendered diabetic by i.v. injection of streptozotocin. The nociceptive behavioral responses to i.t. injection of somatostatin (SST) but nor substance P (SP) were attenuated in diabetic mice compared with that in non-diabetic mice. Spantide, a SP receptor antagonist, enhanced the nociceptive response induced by i.t. SST in diabetic mice. Pretreatment of mice with SP reduced the SST-induced nociceptive response in non-diabetic mice. These results suggest that a endogenous antinociceptive system may exist which links SP with SST-mediated nociceptive transmission in the spinal cord. Furthermore, this endogenous antinociceptive system may be enhanced in diabetic mice.

Animals↗

PubMed1993

Serum glucose level-dependent and independent modulation of mu-opioid agonist-mediated analgesia in diabetic mice.

We examined the effect of insulin on the analgesic potency of DAMGO, a selective agonist of mu-opioid receptors, in mice which had been rendered diabetic by an injection of streptozotocin (STZ; 200 mg/kg, i.v.) 1 and 2 weeks previously. The analgesic potency of DAMGO, based on the tail-flick test, was significantly decreased in both the 1 and 2-week diabetic mice as compared to its effect in age-matched controls. Sensitivity to the analgesic potency of DAMGO returned to normal when insulin was administered to STZ-induced 1-week diabetic mice. However, pretreatment with insulin had no significant effect on the sensitivity to the analgesic potency of DAMGO in 2-week diabetic mice. These results suggest that the serum glucose levels may possibly be responsible for the altered potency of mu-opioid agonists only during the incipient stages of diabetes.

Analgesics↗

PubMed1993

Changes in endothelium-dependent relaxation and levels of cyclic nucleotides in the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats.

The influence of diabetes on the function of vascular endothelium was examined with respect to the role of nitric oxide (NO) in the regulation of blood pressure (BP) in vivo, the vascular relaxation, and levels of cAMP and cGMP in the effluent of the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats. An intravenous injection of 100 mg/kg N omega-nitro-L-arginine methylester (L-NAME) caused hypertension in both diabetic rats and controls. However, the degree of hypertension in the diabetic rats was significantly lower than that in the controls. Acetylcholine (ACh)-induced vasorelaxation of the perfused mesenteric arterial bed decreased in diabetic rats. At the same time, the levels of cAMP and cGMP in the effluent of the diabetic rats were also lower than in the controls. These data indicate that NO formation is involved in the regulation of BP in rats, and is decreased in diabetic rats, due to an impairment of the vascular endothelium, including the endothelium of resistance vessels.

Animals↗

PubMed1993

Endothelium-dependent vasodilator effects of the extract from Salviae Miltiorrhizae radix. A study on the identification of lithospermic acid B in the extracts.

1. The aqueous extract of Salviae Miltiorrhizae radix (Chinese crude drug named "dan-shen") relaxed the noradrenaline-precontracted aorta with endothelium. 2. Vasodilation by the extract disappeared in aorta without endothelium, and was inhibited by pretreatment with 10(-4) M NG-monomethyl-L-arginine (L-NMMA) or 10(-5) M methylene blue. 3. The inhibition of the extract-induced vasodilation by L-NMMA was reversed by L-arginine (3 x 10(-4) M). 4. The component of the extract was analyzed by chromatography, fast atom bombardment mass spectroscopy (FAB-MS) and 1H-NMR. 5. An active component of the extract, which showed endothelium-dependent vasodilation, was found to be identical with lithospermic acid B.

Acetylcholine↗

PubMed1993

Changes in contractile responses of the urinary bladder to substance P in streptozotocin-induced diabetic rats.

1. Functional changes in the urinary bladder obtained from streptozotocin-induced diabetic rats were investigated by determining the responsiveness of bladder strips to capsaicin or substance P (SP). 2. Contractile responses of detrusor strips of the urinary bladder in response to capsaicin were almost abolished in both diabetic rats and capsaicin-pretreated rats. 3. Maximal contractions of diabetic detrusor strips induced by SP were significantly increased when compared to age-matched controls. 4. In contrast to the contractile responses to SP, the density of SP receptors was significantly decreased in diabetic rats. 5. The increased contractile responses to SP were markedly decreased by treatment with indomethacin, OKY-046 or quinacrine, but not with nordihydroguaiaretic acid. 6. Contractile responses of detrusor strips to prostaglandin F2 alpha and E2 were unchanged in the diabetic state. 7. These results suggest that the increased contractile responses of detrusor strips of the bladder to SP in the diabetic state are due to increased synthesis of prostaglandins and/or thromboxane A2 via the increased activity of phospholipase A2 on the smooth muscle of the diabetic bladder.

Animals↗

PubMed1993

Studies on the hypotensive mechanisms of NZ-105, a new dihydropyridine derivative, in rats and rabbits.

1. Intravenous administration of NZ-105 caused a slow-onset and long-lasting hypotension in anesthetized SHR. 2. Centrally administered NZ-105 (0.04 mg/kg) slightly decreased blood pressure. 3. The hypotension of NZ-105 (0.1 mg/kg, i.v.) was not affected by atropine, propranolol, diphenhydramine plus cimetidine, aminophylline or indomethacin. 4. In ganglion-blocked rats, NZ-105 (0.003-0.3 mg/kg, i.v.) inhibited the pressor response to several hypertensive agents to a similar degree. 5. In pithed SHR, NZ-105 (0.03 mg/kg, i.v.) showed the same degree of hypotensive action as in non-treated SHR. 6. NZ-105 did not inhibit reflex responses to tilting in conscious rabbits. 7. Thus NZ-105 exerts its hypotensive action through the mechanisms of peripheral origin.

Animals↗

PubMed1993

Mechanism of the contractile response to platelet-activating factor (PAF) of the rat stomach fundus. I. PAF-induced contractile response and calcium mobilization.

1. Platelet-activating factor (PAF) caused contraction of the rat stomach fundus in a concentration-dependent manner in the presence of atropine, guanethidine, chlorpheniramine, methylsergide, indomethacin, nordihydroguaiaretic acid and tetrodotoxin. 2. PAF produced phasic contraction followed by tonic contraction. The PAF-induced tonic contraction was significantly reduced by treatment with CV-6209, an antagonist of PAF, but phasic contraction induced by PAF was rather resistant to CV-6209. 3. The contraction induced by PAF was markedly reduced when tissues were previously exposed to PAF (desensitization). 4. Nicardipine reduced the PAF-induced phasic contraction but not of the tonic contraction. 5. PAF-induced contractions were almost abolished in Ca(2+)-free medium. 6. The Ca(2+)-contraction in Ca(2+)-free solution was significantly augmented by PAF, whereas the Ca(2+)-contraction in Ca(2+)-free, isotonic high K+ (60 mM) medium was unaffected by PAF. 7. These results suggest that PAF-induced contractile response in the rat stomach fundus is due to an influx of Ca2+ through voltage-dependent Ca(2+)-channels (VDC) and receptor-operated Ca(2+)-channels (ROC). It is further suggested that PAF may depolarize the stomach fundus and this depolarization may open the VDC, whereas PAF may not act directly on the VDC.

Animals↗

PubMed1993

Mechanism of the contractile response to platelet-activating factor (PAF) of the rat stomach fundus. II. PAF-induced phosphatidylinositol turnover and desensitization.

1. Accumulation of [3H]-inositol phosphates (IPs) was slightly enhanced by PAF in a concentration-dependent manner, but the accumulation was very small as compared with that induced by carbachol. 2. The levels of [32P]-phosphatidic acid which is transformed from diacylglycerol (DAG) were increased by treatment with PAF or with carbachol. 3. PAF-induced contraction was significantly reduced by treatment with phorbol 12-myristate 13-acetate (PMA). 4. These results suggest that while PAF slightly stimulates the turnover of phosphatidylinositol (PI) in the rat stomach fundus, this response may not be responsible for the PAF-induced contractile response, and that the desensitization induced by repeated application of PAF may be due to the activation of protein kinase C.

Animals↗

PubMed1993

Involvement of nitric oxide pathway in non-adrenergic non-cholinergic (NANC) relaxation in the rat stomach: differential innervation of NANC nerves in the longitudinal and circular muscle of the fundus.

1. The effects of NG-nitro-L-arginine (L-NNA) on non-adrenergic, non-cholinergic (NANC) relaxation elicited by transmural nerve stimulation (TNS) or high K+ were studied in the rat stomach fundus in order to investigate the mode of innervation of NANC nerves in the longitudinal and the circular muscle of the fundus. 2. Relaxation responses of the fundus to TNS were larger in circular than in longitudinal muscle strips. 3. Treatment with L-NNA (10(-5) M) reduced slightly but significantly the relaxation induced by TNS in both circular and longitudinal muscle strips of the fundus. The inhibitions of the TNS-induced relaxation by L-NNA were reversed partly by L-arginine (10(-3) M). 4. Although K+ produced concentration-dependent contraction in longitudinal muscle strips of the fundus, low concentration of K+ (20 mM) produced rapid and long-lasting relaxation in circular muscle strips of the fundus. 5. The 20 mM of K(+)-induced relaxation in circular muscle strips was significantly inhibited by L-NNA (10(-5) M) or oxyhemoglobin (2 x 10(-5) M). The inhibition of the K+ (20 mM)-induced relaxation by L-NNA was reversed by L-arginine (10(-3) M). 6. These results suggest that NO is one of mediators or transmitters in the NANC relaxation of the rat fundus, and that the density of NO-containing NANC nerves in the stomach fundus is richer in circular than in longitudinal muscle.

Animals↗

PubMed1993

Cough induced activity of spirapril in rats.

1. We examined the effect of spirapril, a potent angiotensin converting enzyme (ACE) inhibitor, on the number of capsaicin-induced coughs in rats and compared with that of enalapril. 2. Chronic treatment with enalapril, at doses of 1 and 3 mg/kg, p.o., significantly and dose-dependently enhanced the number of capsaicin-induced coughs. 3. Chronic treatment with higher dose of spirapril (3 mg/kg, p.o.) also significantly enhanced the number of capsaicin-induced coughs. However, lower dose (1 mg/kg, p.o.) of spirapril had no significant effect on the number of capsaicin-induced coughs. 4. These results suggest that cough induced activity, one of the most serious side effects associated with chronic treatment with ACE inhibitors, of spirapril is relatively lower than that of enalapril.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Effects of long-term oral administration of NZ-105, a novel calcium antagonist, with or without propranolol in spontaneously hypertensive rats.

A new calcium antagonist, NZ-105 ((+/-)-2-[benzyl(phenyl)amino]ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorina n-2-yl)-4- (3-nitrophenyl)-3-pyridinecarboxylate hydrochloride ethanol) (10 mg kg-1, p.o.), showed slow-onset hypotensive effect in spontaneously hypertensive rats (SHRs). The tachycardia evoked by NZ-105 was completely prevented when combined with a beta-adrenoceptor blocker, propranolol (20 mg kg-1), which did not affect the hypotensive response to NZ-105. In long-term administration experiments for 12 weeks with SHRs, the systolic blood pressure in the control group increased with age and the heart rate was stable throughout the period. NZ-105 (10 mg kg-1 day-1) alone and its combined treatment with propranolol (20 mg kg-1 day-1) maintained the systolic blood pressure and heart rate at a low level compared with the control group. The hypotensive action of NZ-105 were reproducible after repeated dosing for 12 weeks. Long-term administration of propranolol affected neither the elevation of the systolic blood pressure nor the heart rate substantially. The heart weight per body weight was significantly reduced after the chronic combination of both drugs, suggesting that the cardiac hypertrophy accompanying hypertension was prevented.

Administration, Oral↗

PubMed1993

Inhibitory effect of NZ-105, a 1,4-dihydropyridine derivative, on cyclic nucleotide phosphodiesterase activity.

The effects of NZ-105, a 1,4-dihydropyridine calcium antagonist, on the intracellular cyclic nucleotide system were investigated in-vitro. In rabbit isolated aorta, both NZ-105 (1 and 10 microM) and nicardipine significantly and in a concentration-dependent manner increased intracellular cyclic AMP and cyclic GMP content. NZ-105 inhibited bovine cardiac phosphodiesterase activity (Ki 30 microM) by competitive antagonism. The concentration ranges for inhibition were consistent with the range of increases in cyclic nucleotides.

1-Methyl-3-isobutylxanthine↗

PubMed1993

Preparation of peptide-carrying microspheres with bioactivity on platelets.

A tetrapeptide RGDS (Arg-Gly-Asp-Ser), which is one of the active sites of cell adhesive proteins, was synthesized according to the solution method and covalently coupled onto monodisperse microspheres. The biospecific activity of the RGDS-carrying microspheres was investigated by measuring the stimulatory effect of the microspheres on platelets. Large and tightly packed platelet aggregation accompanied with drastic ATP release was induced by the RGDS-carrying microspheres. It was confirmed that the specific platelet aggregation was attributed to the activity of the immobilized RGDS by comparison with those induced by other microspheres.

Acrylamides↗

PubMed1993

Effects of mexiletine on formalin-induced nociceptive responses in mice.

We investigated the effect of mexiletine on the formalin-induced nociceptive response and its modulation by diabetes. We also investigated the effects of mexiletine on intrathecally-administered substance P- and somatostatin-induced nociceptive responses in both non-diabetic and diabetic mice. Intraperitoneal injection of mexiletine (30 mg/kg) significantly reduced the duration of the formalin-induced nociceptive response in both non-diabetic and diabetic mice. When mexiletine (30 mg/kg, i.p.) was injected 30 min before injection of substance P (SP), it significantly inhibited SP-induced nociceptive responses in both non-diabetic and diabetic mice. Furthermore, mexiletine also significantly inhibited the intensity of somatostatin (SST)-induced antinociceptive effect of mexiletine in diabetic mice involves the inhibition of SP- and SST-mediated nociceptive transmission in the spinal cord.

Animals↗

PubMed1993

Phorbol ester (PMA)-induced biphasic contraction of the rat aorta and effects of sodium nitroprusside and forskolin on the contraction.

Effects of sodium nitroprusside (SNP) and forskolin on the contractile responses of aortic strips to phorbol 12-myristate 13-acetate (PMA) were investigated in the present study. PMA produced biphasic contraction in the rat aorta, i.e. sustained, slowly developing contraction followed by phasic contraction superimposed on the sustained contraction. Both sustained contraction and phasic response were completely abolished by treatment with staurosporine. Phasic contraction was completely inhibited by nicardipine or removal of external Ca2+, whereas sustained contraction was not affected by nicardipine. Both SNP and forskolin inhibited sustained contraction. Ca(2+)-induced contraction of the aorta which had been treated with PMA in Ca(2+)-free medium was completely inhibited by nicardipine and was partially inhibited by forskolin, but SNP had no effect on the Ca(2+)-contracture. These results suggest that 1) PMA contacts the rat aorta through stimulation of protein kinase C and activation of voltage-dependent Ca2+ channels; 2) there may be great differences in the effects of cyclic GMP and cyclic AMP on the protein kinase C-induced sustained and phasic contractions.

Adenylyl Cyclases↗

PubMed1993

Phorbol ester (PMA) activates voltage-dependent Ca(2+)-channels in helical but not ring preparation of the rat aorta.

Effects of phorbol 12-myristate 13-acetate (PMA) on the helical and ring preparations from rat thoracic aorta was investigated in the present study. In helical strips, PMA produced biphasic contraction, i.e., sustained contraction followed by a phasic response superimposed on the sustained contraction. The phasic contraction was completely inhibited by removal of external Ca2+, whereas sustained contraction was not affected by the treatment. In the ring preparation, PMA produced only sustained contraction, whereas phasic contraction was not induced. On the other hand, in the ring preparation which had been treated with 15 mM K+, PMA was able to produce phasic contraction. Contractile response of the aorta to norepinephrine (NE) or clonidine in the ring preparations was significantly weaker than that in the helical strips. In the presence of nifedipine, however, these different sensitivity to NE between ring and helical preparations was not shown. These results suggest that an activation of C-kinase by PMA is able to stimulate voltage-dependent Ca(2+)-channels in the helical strips but not ring preparation of the aorta. An increased contractile response of the aorta to agonists in helical strips may be responsible for an increased activities of voltage-dependent Ca(2+)-channels.

Animals↗