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Biomedical subjects

Y Kasuya

Publications and source records attributed to Y Kasuya.

At least 271 records · Page 15Linked to original sources
PubMed1988

Changes in sensitivity of the rat stomach fundus to various drugs in streptozotocin-induced diabetic rats.

The changes in sensitivity of the rat stomach fundus to acetylcholine (ACh), norepinephrine (NE), isoproterenol (ISO) and to vasoactive intestinal peptide (VIP) were examined in control rats and in streptozotocin (STZ)-induced diabetic rats. The dose-response curves for drugs were constructed 8 weeks after treatment with STZ. The dose-response curve for ACh in diabetic rats was shifted to the left as compared to the control curve, whereas the dose-response curves for NE, ISO and VIP were shifted to the right. These results suggest that functional changes in the autonomic nervous systems of the rat stomach fundus may occur in STZ-induced diabetic rats.

Acetylcholine↗
PubMed1987

Dopaminergic control of the cough reflex as demonstrated by the effects of apomorphine.

The effect of apomorphine on the cough reflex induced by electrical stimulation of the superior laryngeal nerve was studied in cats anesthetized with pentobarbital. Intravenous administration of apomorphine in doses which ranged from 0.1 to 1.0 mg/kg decreased the number of coughs in a dose-dependent manner. Haloperidol (0.3 mg/kg i.v.) did not significantly change the number of coughs. However, haloperidol administered 15 min prior to administration of apomorphine abolished the apomorphine-induced decrease in the number of coughs. These results suggest that dopaminergic mechanisms could have an important role in the regulation of the cough reflex.

Animals↗
PubMed1987

Atrophy of the striatum and motor disturbance induced by colchicine.

To determine the functional role of the striatonigral system in the circling behavior of rats and the mode of action of colchicine, we investigated the circling behavior induced by dopamine agonists after microinjection of colchicine into the unilateral striatum. Both apomorphine and methamphetamine produced ipsilateral circling behaviors in rats injected with colchicine, indicating that ipsilateral striatonigral pathways were damaged by the drug. Histological and biochemical examinations showed that intracaudate injection of colchicine damaged not only the dopaminergic neurons but also caused atrophy of the striatum with loss of neuronal perikarya. These results suggest that treatment with colchicine may be used as a model of senile atrophy or degenerative atrophy in these animals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Determination of stable isotopically substituted histidine in human plasma by gas chromatography-mass spectrometry.

A gas chromatographic-electron-impact mass spectrometric method for the determination of stable isotopically substituted histidine in human plasma has been developed. Histidine was derivatized to alpha N-trifluoroacetyl-imN-carbethoxyhistidine n-butyl ester (TCB derivative) by a three-step reaction: an initial esterification by 3 M n-butanolic hydrochloric acid, followed by trifluoroacetylation with trifluoroacetic anhydride and then ethoxycarbonylation with diethyl pyrocarbonate. Quantitation was carried out by selected-ion monitoring on the molecular ions (m/z 379, 383 and 385) of the respective TCB derivatives of histidine, [1-15N,5,beta,beta-2H3]histidine (histidine-[M + 4]) and [1,3-15N2,5,alpha,beta,beta-2H4]histidine (histidine-[M + 6]). The sensitivity, specificity, precision and accuracy of the method were demonstrated to be satisfactory for application to a pharmacokinetic study of histidine after administration of a trace amount of stable isotopically substituted histidine (histidine-[M + 4]) in humans.

Chemical Phenomena↗
PubMed1987

Contractile response and electrophysiological properties in enzymatically dispersed smooth muscle cells of rat vas deferens.

Electrophysiological studies were performed on single smooth muscle cells isolated from the vas deferens of the rat. The tissue was preincubated in Ca-free modified Tyrode's solution for 1 h and then transferred to a high-K solution for 1 h. It was next minced and treated with the enzyme solution composed of 600-800 unit/ml collagenase and 40 unit/ml elastase. The procedure yielded about 50% spindle shaped Ca-tolerant cells (100-250 microns in length and about 10 microns in diameter). These cells could contract during the superfusion with the solutions containing 10(-8) to 10(-3) M norepinephrine (NE) or adenosine triphosphate (ATP). The cells isolated from the epididymal portion were more sensitive to norepinephrine than were those from the prostatic part. Their basic electrical properties were studied using tight-seal suction electrode technique. The cells had resting potentials around -40 mV and their input resistance was about 0.8 G omega. Action potentials could be evoked by application of depolarizing current. During whole cell voltage clamp, an inward current followed by an outward current was recorded when 800 ms pulses from a holding potential of -60 mV to test potentials positive than -40 mV were applied. The transient outward current generally recorded in other smooth muscle cells was not seen in these cells. The amplitude of the inward current was Ca dependent and sensitive to a Ca antagonist, nicardipine, indicating that Ca ion is the main carrier of this component of the current. When the pipette was filled with Cs-containing solution, the outward current was abolished.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1987

Potentiation by bovine serum albumin (BSA) of endothelium-dependent vasodilator response to acetyl glyceryl ether phosphorylcholine (AGEPC).

Endothelium-dependent vasodilator responses of isolated rat aortic strips precontracted with norepinephrine to acetyl glyceryl ether phosphorylcholine (AGEPC) were compared in the presence and absence of bovine serum albumin (BSA). In the absence of BSA, AGEPC produced endothelium-dependent relaxation at concentrations higher than 10(-6) M, which was considered to be non-specific because similar relaxations were produced by other phospholipids (e.g., lysolecithin) at the same concentration range. This non-specific relaxation was suggested to be caused by changes in membrane fluidity of endothelial cells, since high concentrations of AGEPC and other phospholipids were found to produce structural changes in endothelial cells by phase contrast and electron microscopic studies; structural changes were never observed after the application of acetylcholine (ACh). In the presence of BSA (2.5 mg/ml), AGEPC caused endothelium-dependent relaxation at concentrations as low as 10(-9)M; however, relaxations by ACh and lysolecithin were not augmented by the presence of BSA. CV-3988 (10(-5)M), a specific antagonist of AGEPC, inhibited the relaxations by AGEPC in the presence of BSA. From these results, it is suggested that, in the presence of BSA, AGEPC may produce endothelium-dependent relaxation in a specific manner, which is different from the non-specific relaxations observed in the absence of BSA.

Animals↗
PubMed1987

Pharmacological and electrophysiological discrimination of contractile responses to selective alpha 1- and alpha 2-adrenoceptor agonists in rat tail artery.

Pharmacological and electrophysiological properties of postsynaptic alpha-adrenoceptor subtypes in rat tail artery were compared using selective alpha 1- and alpha 2-adrenoceptor agonists. Five alpha-adrenoceptor agonists contracted the tail artery with the following order of maximal effects: norepinephrine (alpha 1 and alpha 2) greater than methoxamine (alpha 1) = phenylephrine (alpha 1) much greater than clonidine (alpha 2) greater than UK-14,304 (alpha 2). Phenoxybenzamine greatly diminished contractions induced by methoxamine and phenylephrine, but had little effect on responses to UK-14,304. Idazoxan antagonized more potently against UK-14,304 than against methoxamine. These results suggest the heterogeneity of postsynaptic alpha-adrenoceptors in the rat tail artery. Furthermore, responses to methoxamine and phenylephrine 1) had faster onsets and 2) were more resistant to Ca2+ entry blockers, nicardipine and diltiazem, and a promotor, Bay K 8644, or decreasing of extracellular Ca2+ and 3) were more sensitive to a calmodulin antagonist, W-7, than the responses to UK-14,304 and clonidine. Both methoxamine and UK-14,304 depolarized the membrane but methoxamine produced stronger depolarization than UK-14,304. Therefore, the high sensitivity of alpha 2-adrenoceptor agonists-induced responses to Ca2+ entry blockers and promotors cannot be accounted for solely by membrane depolarization. These results may indicate the differences in the Ca2+ movement for the contractions produced by alpha 1- and alpha 2-adrenoceptor agonists.

Adrenergic alpha-Agonists↗
PubMed1987

Are alpha-adrenoceptors involved in positive inotropic effects of phenylephrine in chick ventricles?

Effects of phenylephrine on contraction and Ca-action potentials were investigated to clarify whether the alpha-adrenergic mechanism may play a role in chick ventricles. Phenylephrine increased the contractile force of the ventricles isolated from both embryonic and hatched chicks, while methoxamine did not affect their contractility. Developmental changes in the sensitivity to phenylephrine, i.e., increase with age from late embryonic to early neonatal stages, were quite similar to those to a beta-agonist, isoproterenol. The positive inotropism of phenylephrine was antagonized by phentolamine and sotalol, but not antagonized by prazosin or yohimbine. Isobutylmethylxanthine augmented the effect of phenylephrine. Maximum upstroke velocity of Ca-action potentials recorded in partially depolarized ventricles were enhanced by phenylephrine, and the enhancement was eliminated by sotalol but not by phentolamine. The results suggested that the beta-adrenergic action of phenylephrine may be involved in part of its positive inotropic effect, which is mediated by increased Ca-influx through sarcolemma. Another mechanism may also participate in the effects of phenylephrine, but may not necessarily be classified as an "alpha-adrenergic effect".

Animals↗
PubMed1987

Monoamines and the mechanisms of action of antitussive drugs in rats.

The influence of drugs which modify the concentration of brain monoamines on the size of the 50% antitussive dose (AtD50) of morphine (M), dihydrocodeine (DC) and dextromethorphan (DX) was investigated in male Sprague-Dawley rats. The puncture electrode-induced cough method was used for inducing cough. The AtD50 was calculated by the "up and down" method. All drugs were injected i.p. Concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in the whole brain were measured by means of high performance liquid chromatography with electro-chemical detection. The values for the AtD50 of M, DC and DX were 1.22, 1.44, and 6.06 mg/kg, respectively. Reserpine (2.5 mg/kg/day, 2 days) produced depression of more than 80% in levels of NE, DA and 5-HT in the brain. This treatment resulted in a substantial reduction in the antitussive effect of the cough suppressants, as evidenced by an increase in the AtD50 of M, DC and DX. p-Chlorophenylalanine (PCPA; 300 mg/kg, 24 hr) specifically produced a reduction of more than 70% in the level of 5-HT in the brain. The PCPA-treated rats also displayed an inhibition of the antitussive effect. The AtD50 in reserpine- and PCPA-treated rats was 2- and 4-fold higher, respectively, than the AtD50 for normal rats. alpha-Methyl-p-tyrosine (300 mg/kg, 5 hr) produced a significant reduction in the levels of NE and DA in the brain, but the antitussive effects of M, DC and DX were not altered. These results suggest that 5-HT in the brain may play an important role in the mechanism of action of antitussive drugs.

Animals↗
PubMed1986

Stable-isotope methodology in the bioavailability study of 17 alpha-methyltestosterone using gas chromatography-mass spectrometry.

The application of a stable-isotope coadministration technique for estimating the relative bioavailability of 17 alpha-methyltestosterone is described. Eight healthy male subjects were administered orally a single 10-mg 17 alpha-methyltestosterone tablet together with a 10-mg 17 alpha-methyltestosterone-d3 solution. The serum concentrations of 17 alpha-methyltestosterone and 17 alpha-methyltestosterone-d3 were determined by gas chromatography-mass spectrometry with selected ion monitoring using 17 alpha-methyltestosterone-d6 as an internal standard. The extent of absorption from the tablet formulation was comparable to that from the oral solution. The stable-isotope methodology was compared with the conventional cross-over method for evaluating the bioavailability of 17 alpha-methyltestosterone.

Absorption↗
PubMed1986

Attenuation of the development of hypertension in spontaneously hypertensive rats by chronic oral administration of eicosapentaenoic acid.

Chronic effects of highly purified eicosapentaenoic acid (EPA) on systolic blood pressure in spontaneously hypertensive rats (SHR) and normotensive rats were studied. Daily oral administration of 30 to 300 mg/kg EPA for eight weeks significantly decreased the development of hypertension in SHR dose-dependently. Eight weeks treatment of 30, 100, and 300 mg/kg EPA reduced mean systolic blood pressure by 23, 29, and 32 mmHg, respectively, compared to untreated rats. Hypotensive effect of EPA progressed slowly and was reversible after the termination of the treatment. However, daily administration of EPA to normotensive rats did not affect the systolic blood pressure. EPA may be useful as a hypotensive agent for treatment of hypertension.

Animals↗
PubMed1986

Pharmacological studies of imidazoline derivatives. I. A comparison of the effect on pre- and postsynaptic alpha-adrenoceptors in the rat vas deferens.

The effects of 8 imidazoline derivatives on pre- and postsynaptic alpha-adrenoceptors and [3H]norepinephrine release were investigated in the rat vas deferens and were compared with those of reference drugs, yohimbine, phentolamine, tolazoline, and prazosin. K-6341 and K-6343 activated postsynaptic alpha 1-adrenoceptor and were antagonized by prazosin. The order of potency series as alpha 1-antagonist, prazosin greater than phentolamine greater than yohimbine greater than K-4011 greater than K-3827 greater than K-4300, tolazoline was found in antagonism against phenylephrine. Many derivatives exhibited an antagonistic action against clonidine, and the potency series as alpha 2-antagonist was revealed as follows: phentolamine greater than yohimbine greater than K-3827 greater than K-4011 greater than K-6341 greater than K-6343 greater than K-4300, tolazoline greater than prazosin greater than K-4299. The antagonistic effect was more selective on presynaptic (alpha 2) than postsynaptic (alpha 1) adrenoceptor and the rank order of selectivity (KB-post/KB-pre) was K-3827 greater than yohimbine greater than K-4011 greater than tolazoline, K-4300 greater than phentolamine greater than prazosin. Imidazoline derivative increased [3H]norepinephrine release, the actions of K-3827, K-6341 and K-4300 being particularly potent. From these results, the structure-activity relationship was summarized. First, when 2',3'-methylenedioxyphenyl group is connected with the imidazoline ring via an amino or methylene residue, these compounds become alpha 1-agonist. Secondly, when the methylenedioxyphenyl group and the imidazoline ring are connected via an amino residue, these compounds show a weak agonistic and potent antagonistic characteristics at the presynaptic alpha 2-adrenoceptor. Thirdly, an addition of a methylenedioxy radical to the phenyl ring increased the affinity of the compounds to presynaptic alpha 2-receptor.

Animals↗
PubMed1986

Pharmacological studies of imidazoline derivatives. II. Agonistic and antagonistic actions on alpha-adrenoceptors in various smooth muscle preparations.

The effects of 8 imidazoline derivatives on alpha-adrenoceptor-mediated contraction or relaxation of various kinds of smooth muscle preparations were investigated. In rabbit aortic strips, K-6341, K-6343 and K-4011 produced alpha-agonistic action which was antagonized by prazosin. In the study of alpha-antagonistic action of imidazoline derivatives, i.e. antagonism against norepinephrine- or phenylephyrine-induced contraction of the rabbit aortic strip, the order of potency series, prazosin greater than phentolamine greater than yohimbine greater than K-4011, K-3827, K-4300 greater than tolazoline was found. Reserpine pretreatment did not affect the results. In the study of alpha-antagonistic effect on the relaxing response to norepinephrine of methacholine-contracted rat ileum, the potency series was revealed as follows: prazosin greater than phentolamine greater than yohimbine greater than K-4011, K-3827, K-4300, tolazoline. A similar experiment was performed on histamine-contracted guinea-pig taenia coli, and the results were nearly identical to the case of the rat ileum, except that K-6341 and K-6343 also exhibited alpha-antagonistic action which was not detected in the rat ileum. This suggests that alpha 2-receptor may exist in the postsynaptic alpha-adrenoceptor in the guinea-pig taenia coli. The results of the present study indicate that the potency of imidazoline derivatives to inhibit norepinephrine-induced contraction of some smooth muscle is almost identical to that which inhibited norepinephrine-induced relaxation of other smooth muscles. Furthermore, K-4300 was found to possess anti-acetylcholine and anti-histamine actions in the guinea-pig taenia coli and anti-serotonin action in the rat fundus strips.

Acetylcholine↗
PubMed1986

Pharmacological studies of imidazoline derivatives. III. Actions on cardiovascular system and acute toxicity.

The effects of 8 imidazoline derivatives on the cardiovascular system and their acute toxicity were investigated. In anesthetized rats, K-6341 and K-6343 produced relatively long-lasting elevation of blood pressure. This hypertensive response was prevented by prazosin. In contrast, K-4011, K-3827 and K-4300 exerted long-lasting hypotensive actions. Norepinephrine-induced increase in blood pressure was competitively antagonized by these three derivatives. Therefore, the hypertensive and hypotensive actions of imidazoline derivatives are conceivably exerted by activating and blocking alpha 1-adrenoceptors. In the isolated guinea-pig atrial preparations, K-4011, K-3827, K-6341 and K-6343 produced positive inotropic responses which were independent of beta-adrenoceptor activation. The positive inotropic effect of K-6341, which was the most potent, was specifically attenuated or abolished by diltiazem, suggesting that a change in Ca2+ movement across the cell membrane is contributing to K-6341-induced increase in atrial contractions. The main symptoms of mice manifested when injected with imidazoline derivatives were a decrease in spontaneous movement, exophthalmos, an increase in palpebral opening, paralysis of four limbs and respiratory depression. Acute LD50 values of imidazoline derivatives in mice (i.v., i.p.) were between these of tolazoline and naphazoline.

Animals↗
PubMed1986

Effects of cocaine and tetraethylammonium on the spike potentials and contractions induced by transmural stimulation in the rat vas deferens.

Effects of cocaine and tetraethylammonium (TEA) on the spike potential induced by transmural nerve stimulation were investigated with microelectrodes in smooth muscle cells of rat vas deferens. Resting membrane potential was not changed by 10(-5) M cocaine. 10(-5) M cocaine reduced the amplitudes of spontaneous excitatory junction potentials and diminished generation of excitatory junction potentials induced by nerve stimulation. However, cocaine did not affect the electrophysiological parameters of spike potentials; overshoot potential, threshold potential and duration of spikes were not changed by cocaine. Cocaine slightly inhibited the twitch contractions to transmural nerve stimulation. In contrast, 1-5 mM TEA increased the overshoot potentials and prolonged the duration of spikes dose-dependently without changing the resting membrane potential. Twitch contractions to transmural nerve stimulation were greatly enhanced by 2.5 mM TEA. These results suggest that TEA, but not cocaine, may increase the Ca-influx which is believed to occur during spike generation in the smooth muscle cells of vas deferens.

Action Potentials↗
PubMed1986

Inhibitory action of propranolol on the contractions induced by nerve stimulations or calcium in the smooth muscle of rat vas deferens.

Inhibitory effects of propranolol on the contractions to various treatments were investigated in the epididymal half of the rat vas deferens. Reportedly, 10(-5)-3 X 10(-4) M propranolol inhibited 150 mM K-induced contractions dose-dependently; 3 X 10(-4) M propranolol abolished the contractions. The present results showed that propranolol at concentrations up to 10(-4) M did not inhibit the maximal contractions to 10(-3) M norepinephrine (NE) or 10(-2) M methacholine (MCh). Propranolol at 3 X 10(-4) M slightly inhibited contractions to NE and MCh by 11% and 12%, respectively. In contrast, propranolol inhibited twitch components of the contractions induced by nerve stimulations at similar doses to those reported for high K contractions. Propranolol also inhibited contractions to Ca in high K-containing solution and shifted the dose-response curve to the right. Propranolol did not affect the depolarizations by high K measured by microelectrodes. Propranolol at concentrations of 10(-5)-3 X 10(-5) M diminished the magnitude of spikes dose-dependently. Spikes were rarely observed in the presence of 10(-4) M propranolol in spite of generation of e.j.p.s with amplitudes that would be sufficient to induce spikes in the absence of propranolol. These results suggest that propranolol inhibits contractions by decreasing Ca-influx through the potential-operated Ca-channels in the smooth muscle cells of rat vas deferens.

Animals↗