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Biomedical subjects

T Yoshitomi

Publications and source records attributed to T Yoshitomi.

At least 55 records · Page 3Linked to original sources
PubMed1993

The presence of two sites of action of endothelins in the isolated rabbit iris sphincter and dilator muscles.

The contractile activity of endothelins (ETs) and their effect on twitch contraction evoked by electrical field stimulation were studied in the isolated rabbit iris sphincter and dilator muscles using the isometric tension recording method. ET-1, ET-2 and ET-3 caused slow contractile response of the sphincter as well as the dilator muscles, with sphincter muscle EC50 values of 37.3, 58.0 and 84.3 nM, and dilator muscle values of 31.7, 69.0 and 224.4 nM, respectively. These contractile responses were not affected by atropine (1 microM), prazosin (1 microM) or indomethacin (1 microM). ET-1 and ET-3 slightly but significantly inhibited the fast cholinergic component of twitch contraction of the sphincter muscle evoked by field stimulation, without affecting the response to carbachol. However, ET-1 did not affect the slow substance P-ergic component of twitch contraction of this preparation. In the dilator muscle, ET-1 and ET-3 had little effect on the contraction induced by phenylephrine but reduced the amplitude of the twitch contraction evoked by the field stimulation. The inhibitory effect of ETs on the dilator muscle was antagonized by pretreatment with BQ-123 (100 nM), which is a selective ETA receptor antagonist. Pretreatment with indomethacin (1 microM) also attenuated the inhibitory effect of ETs on the twitch contraction. These results suggest that ETs may have two sites of action, pre- and post-synaptic effects, on the rabbit iris sphincter muscle as well as the dilator muscle. All three ET isopeptides may have direct contractile activity on the smooth muscles of the sphincter as well as the dilator without mediation by prostaglandins or neuronal mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Decreased hypothalamic and medullary GABA turnover in spontaneously hypertensive rats.

OBJECTIVE: The aim was to assess whether Gamma-aminobutyric acid (GABA) neurone activities in the central nervous system, especially in the hypothalamus and medulla oblangata, are altered in hypertension. METHODS: Central GABA content and turnover rate were measured in spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto controls (WKY). GABA content was determined with high performance liquid chromatography, and in vivo GABA turnover rates were estimated by GABA accumulation after injection of amino-oxyacetic acid, a selective inhibitor of GABA degrading system. Two groups of nine week old male rats (32 SHR and 32 WKY) were used. RESULTS: GABA concentrations in cerebrospinal fluid were lower in SHR than in WKY. Since hypothalamus and medulla oblongata are the possible active sites of this system, basal GABA contents and in vivo GABA turnover rates were measured in hypothalamus and medulla oblongata. Basal GABA content in the medulla oblongata and hypothalamus was almost equal in SHR and WKY. On the other hand, GABA turnover rates were significantly lower in SHR than in WKY in both the hypothalamus and the medulla. CONCLUSIONS: Since it is known that GABA is an inhibitory neurotransmitter in the central nervous system and that it controls autonomic and cardiovascular activities, the findings suggest that the decreased hypothalamic and medullary GABAergic activities may permit sympathetic hyperactivity to contribute to the increase in blood pressure in SHR.

Aminooxyacetic Acid↗
PubMed1992

Do alpha-adrenergic receptors participate in control of the circadian rhythm of IOP?

The alpha 2-adrenergic antagonists, yohimbine and rauwolscine, and the alpha 1-adrenergic antagonist, bunazosin, were used to explore the role of alpha-adrenergic receptors in the regulation of the circadian rhythms of intraocular pressure and aqueous flow in New Zealand white rabbits. Blockade of alpha 2-adrenergic receptors with yohimbine or rauwolscine produced small decreases in intraocular pressure during both light and dark phases. Rauwolscine had no effect on aqueous flow during the light or dark, but it increased the concentration of norepinephrine in the aqueous during both light and dark. These observations are difficult to reconcile with earlier suggestions that increased sympathetic input to the eye increases intraocular pressure and aqueous flow during the dark. The role of alpha 2-adrenergic receptors in the control of the circadian rhythm of intraocular pressure is unclear. Blockade of alpha 1-adrenergic receptors with bunazosin produced a dose-dependent reduction of IOP during the dark phase of the circadian cycle, a smaller reduction during the light phase, and no reduction during either light or dark in rabbits after superior cervical ganglionectomy or preganglionic section of the cervical sympathetic trunk (decentralization). Bunazosin decreased pupil diameter during the dark phase but had no effect on aqueous flow. Because it is unlikely that alpha 1-adrenergic blockade increased outflow facility or uveoscleral outflow, the mechanism for the role of alpha 1-adrenergic receptors in the control of the circadian rhythm of intraocular pressure in rabbits remains to be identified.

Adrenergic alpha-Antagonists↗
PubMed1991

Ocular adrenergic nerves contribute to control of the circadian rhythm of aqueous flow in rabbits.

Aqueous flow was measured fluorophotometrically in New Zealand white rabbits after unilateral decentralization of the cervical ganglion or cervical ganglionectomy to determine the role of ocular adrenergic input in regulating the circadian rhythm of aqueous flow. Both surgical procedures decreased the rate of aqueous flow during the dark phase when flow is high. During the light phase when flow is low, cervical ganglionectomy increased aqueous flow; decentralization may have increased flow also, but the increases were not statistically significant. Aqueous flow was also measured in normal rabbits after topical application of timolol during the light or dark to determine whether beta-adrenergic receptors play a role in controlling the circadian rhythm of flow. Timolol produced a small reduction of the rate of aqueous flow when applied topically during the dark but not during the light. These results suggest that part of the increase of aqueous flow during the dark phase is produced by adrenergic input to the ciliary processes and that beta-adrenergic receptors mediate part of this increase.

Administration, Topical↗
PubMed1991

Changes in aqueous norepinephrine and cyclic adenosine monophosphate during the circadian cycle in rabbits.

The concentrations of catecholamines and cyclic adenosine monophosphate (AMP) in the aqueous of rabbits entrained to 12-hr light:12-hr dark were measured at six times during the circadian cycle. Aqueous norepinephrine was higher in the dark than in the light; the minimum concentration at 1.5 hr after lights on, and maximum concentration at 6 hr after lights off, were 1.21 +/- 0.17 and 4.60 +/- 0.79 ng/ml, respectively. The concentrations of epinephrine and dopamine were less than the sensitivity of the assay (0.1 and 0.4 ng/ml, respectively) at all times. Aqueous cyclic AMP was also higher in the dark than in the light; the minimum concentration at 6 hr after lights on, and maximum concentration at 10.5 hr after lights off, were 11.5 +/- 1.2 and 29.4 +/- 2.7 pmol/ml, respectively. Superior cervical ganglionectomy reduced aqueous norepinephrine during light and dark to less than the sensitivity of the assay (0.1 ng/ml); preganglionic section of the cervical sympathetic trunk (decentralization) did not reduce aqueous norepinephrine as much as ganglionectomy but markedly reduced its concentration during the light and dark. Superior cervical ganglionectomy or pretreatment with 0.1% timolol virtually eliminated, and decentralization markedly reduced, the dark-phase increase of aqueous cyclic AMP. Most of the daily changes in norepinephrine and cyclic AMP persisted in animals housed in constant dark; this is consistent with the fraction of both changes which persisted in constant dark being circadian. These results support the idea that increased adrenergic activity during the dark increases the rate of aqueous flow and intraocular pressure in rabbits.

Animals↗
PubMed1990

Aqueous flare measurement with laser flare-cell meter.

The laser flare-cell meter is a newly developed instrument designed to measure anterior chamber protein concentration in vivo. There was a linear relationship between photon count measured with this instrument and the concentration of bovine serum albumin. Measurements were taken in 29 eyes of normal subjects divided into two groups. Group 1 (15 eyes) had brown or dark irises and Group 2 (14 eyes) had blue or green irises. Photon counts obtained from Groups 1 and 2 were not significantly different. Aqueous protein concentrations estimated from standard curves were 15.7 and 18.6 mg/100 ml for Groups 1 and 2, respectively. On the other hand, the background value obtained from Group 2 was about twice the value from Group 1. These results indicate that background scattering has little effect on photon count. There was a good correlation between photon counts measured with the laser flare-cell meter and the evaluation of flare made by conventional microscopic observations. It was concluded that this instrument will be useful for clinical research studies.

Adult↗
PubMed1988

Functional innervation and contractile properties of the human iris sphincter muscle.

To investigate the pattern of innervation and the contractile properties of human iris sphincter muscle, we have observed the effects of field stimulation, various drugs and excess-K+ solutions on isometric tension development in strips of the iris sphincter from five humans. Spontaneous mechanical responses were not observed in these tissues. Electrical field stimulation (50 V, 0.8 msec, 20 Hz) evoked a contraction which was abolished by 10(-7) M tetrodotoxin (TTX) or by 10(-6) M atropine, thereby indicating that the response was cholinergically mediated. In the presence of atropine, electrical field stimulation did not affect muscle tone, even when this was elevated by histamine. The effect of exogenously applied noradrenaline (NA) varied among the specimens, i.e. in three out of four cases a contraction was evoked while a relaxation occurred in one preparation. The contraction evoked by NA was blocked by phentolamine (10(-6) M) and the relaxation was blocked by timolol (10(-6) M). Excess-K+ solutions, dose dependently contracted the muscle strips and application of 10(-6) M atropine decreased the amplitude of these contractions. The results indicate that the human iris sphincter is innervated by excitatory cholinergic nerve fibres and that the adrenergic innervation is sparse. In addition, this muscle possesses both alpha and beta adrenoceptors. Activation of alpha receptors produces a contraction whilst activation of the beta adrenoceptors causes relaxation.

Aged↗
PubMed1988

Autoregulation of acetylcholine release from vagus nerve terminals through activation of muscarinic receptors in the dog trachea.

1. The effects of pirenzepine and gallamine on the membrane and contractile properties of smooth muscle cells and on excitatory neuro-effector transmission in the dog trachea were investigated by means of microelectrode, double sucrose gap and tension recording methods. 2. Pirenzepine (10(-7) M) and gallamine (10(-5) M) had no effect on the resting membrane potential or the input resistance of the smooth muscle cells. 3. Pirenzepine (10(-10)-10(-9) M) and gallamine (10(-7) M) enhanced the amplitude of twitch contractions evoked by field stimulation in the combined presence of indomethacin (10(-5) M) and propranolol (10(-6) M). At higher concentrations pirenzepine (10(-8) M) inhibited the twitch contractions in a dose-dependent manner. Both pirenzepine and gallamine in doses over 10(-7) and 10(-5) M, respectively, reduced muscle tone. 4. Pirenzepine (10(-10)-10(-9) M) and gallamine (10(-7) M) enhanced the amplitude of excitatory junction potentials (e.j.ps) evoked by field stimulation (single or repetitive stimulation). However, a high concentration of pirenzepine (10(-8) M) reduced the amplitude of e.j.ps. In parallel with its action on e.j.ps, pirenzepine (over 10(-9) M) reduced the response of smooth muscle cells to acetylcholine (ACh), in a dose-dependent manner. Gallamine (5 X 10(-5) M) markedly enhanced the amplitude of e.j.ps but also reduced the response of muscle cells to ACh. 5. ACh (10(-10)-10(-9) M) inhibited twitch contractions evoked by field stimulation, with a slight increase of resting tension. 6. Gallamine enhanced the summation of e.j.ps during repetitive field stimulation at a high frequency (20 Hz), but was without effect on the depression phenomena of e.j.ps observed during double stimulus experiments at different time intervals (5-60 s). 7. These results indicate that both pirenzepine and gallamine have dual actions on pre- and post-junctional muscarinic receptors in dog tracheal tissue. At low concentrations both agents potentiate excitatory neuro-effector transmission, presumably due to enhancement of release of ACh from vagal nerve terminals through blockade of a negative auto-regulatory process activated by endogenous ACh. At higher concentrations, these agents inhibit the response of smooth muscle cells to ACh through post-junctional muscarinic receptors and relaxation of the muscle tissue occurs.

Acetylcholine↗
PubMed1988

Effects of indomethacin and prostaglandins on the dog iris sphincter and dilator muscles.

Effects of indomethacin and prostaglandins (PGs: PG E1, PG E2 and PG F2 alpha) on electrical and mechanical properties of the dog iris sphincter and dilator muscles were studied using isometric tension recording and microelectrode methods. When field stimulations (50 V, 0.4 msec, 10 stimuli at 10 Hz) were applied every 1 min, the muscle tone was gradually elevated in both muscle tissues. Application of 10(-6) M indomethacin gradually reduced the tone of the muscle tissues; however, this reduction was more pronounced in the sphincter muscle. On the contrary, exogenously applied PG F2 alpha increased the muscle tone in both tissues. Ca-free solution reduced the tone in both muscle tissues. Following pre-treatment with indomethacin, Ca-free solution had no effect on the muscle tone in the sphincter; however, it did reduce the tone in the dilator muscle. Indomethacin (10(-6) M) or PGs (PG E1, PG E2 and PG F2 alpha: up to 10(-7) M) had no effect on the resting membrane potential of both muscles. PG F2 alpha dose-dependently contracted both of the sphincter and dilator muscles. PG E1 and PG E2 had little effect on the mechanical properties of these muscles. Neither atropine nor guanethidine affected the amplitude of contractions evoked by PG F2 alpha. These results suggest that endogenous PG F2 alpha may contribute to maintenance of the muscle tone of the sphincter muscle but contributes to a lesser degree in the dilator muscle in the dog iris. PGs apparently act directly on these muscles rather than through the release of adrenergic or cholinergic neurotransmitters.

Animals↗
PubMed1986

Pre-synaptic actions of noradrenaline on the dog ciliary muscle tissue.

Effects of noradrenaline (NA) on the electrical and mechanical properties of the dog ciliary muscle were investigated using microelectrode- and isometric tension recording methods. Electrical-field stimulation to the tissue evoked excitatory junctional potentials (e.j.ps) followed by twitch contractions. Both responses were abolished by tetrodotoxin (TTX, 10(-7) M) or atropine (10(-6) M), thereby indicating that these responses are cholinergic-related. Exogenously applied NA (greater than 10(-8) M) suppressed the amplitude of e.j.ps and the following twitch contraction evoked by field stimulations, with no change in the resting tension, membrane potential and input membrane resistance of the smooth muscle cells. Exogenously applied carbachol dose-dependently contracted the ciliary muscle. However, NA (10(-5) M) did not affect the carbachol-induced contraction, thereby indicating that NA acts on the nerve terminals and reduces the amount of transmitter released from the terminals. Inhibitory effects of NA on the twitch contraction were antagonized by yohimbine (10(-6) M), but not by prazosin (10(-6) M) or timolol (10(-6) M). Guanethidine (5 X 10(-6) M) had no effect on the contraction evoked by field stimulation. These results provide evidence that exogenously applied NA activates the alpha 2-adrenoceptor located on cholinergic nerve terminal, hence the excitatory neuro-effector transmission is suppressed. These actions may explain the decrease in near point of accommodation observed with clinical application of adrenergic agents.

Animals↗
PubMed1986

Membrane and contractile properties of the dog ciliary muscle.

Membrane properties and excitation-contraction coupling mechanisms of the dog ciliary muscle were investigated by use of microelectrode and isometric tension recording methods. The mean resting membrane potential of the smooth muscle cell was -59.6 +/- 1.6 mV and the membrane was electrically quiescent. With applications of inward and outward current pulses, by the partition stimulating method (pulse duration, 1.0 s), electrotonic potentials, but not action potentials (spike) were evoked even in the presence of tetraethylammonium (TEA, 10 mM). The space and time constants calculated from the current-voltage relationship observed at various distances from the stimulating electrode were 0.43 +/- 0.07 mm (+/- s.d. n = 5) and 82.5 +/- 10.6 ms (+/- s.d. n = 4), respectively. Electrical field stimulation of short duration (50-300 microseconds) evoked excitatory junction potentials (e.j.ps) followed by twitch contraction, both of which were potentiated by neostigmine (10(-7) M) and abolished by tetrodotoxin (TTX, 10(-7) M) or atropine (10(-6) M). However, e.j.ps of amplitude over 3-5 mV did not evoke action potentials. Excess [K]o solution dose-dependently depolarized the membrane (the maximum slope of the depolarizations produced by a tenfold increase in [K]o plotted on a log scale was 52.5 mV) and evoked contractions. Atropine (10(-6) M) had no effect on the [K]o-induced membrane depolarization, however, it greatly reduced the amplitude of [K]o-induced contraction. Nisoldipine (5 X 10(-7) M) had no effect on the contraction evoked by field stimulation, however, this agent suppressed the [K]o-induced contraction to 78.3 +/- 6.8% of the control value. Combined application of nisoldipine and atropine completely inhibited the [K]o-induced contraction. Although the membrane depolarization evoked by carbachol (greater than 10(-7) M) was small (10 mV depolarization at 10(-5) M), the contraction evoked by 10(-5) M carbachol was larger than that evoked by 118 mM [K]o (185 +/- 50%, n = 9). Ca-free 3 mM EGTA-containing solution did not alter the resting tension, but greatly reduced the carbachol-induced contraction (to 8.6 +/- 2.3% of the control value). The present results indicate that the membrane of dog ciliary muscle behaves as an electrical syncytium, and that the contractile responses occur mainly through activation of the receptor-operated Ca channels and partly through activation of voltage-dependent Ca channels.

Animals↗
PubMed1986

Double reciprocal innervations in dog iris sphincter and dilator muscles.

Neuro-effector transmission and mechanical responses in smooth muscles of the dog iris were studied, using tension recording and microelectrode methods. Electrical stimulations evoked an initial phasic contraction followed by relaxation in both the iris sphincter and dilator muscles. Atropine selectively suppressed phasic contraction of the sphincter and relaxation of the dilator muscle, while guanethidine selectively blocked relaxation of the sphincter and contraction of the dilator muscle. Pharmacological investigations revealed distributions of alpha 1-excitatory (mediating contractions) and alpha 2-inhibitory (mediating relaxations) adrenoceptors in addition to beta-inhibitory adrenoceptors in the sphincter muscles, and alpha-excitatory and beta-inhibitory adrenoceptors in the dilator muscle. These results indicate that the iris sphincter and dilator muscles receive double reciprocal innervations by the cholinergic and adrenergic nervous systems. Norepinephrine (NE) or carbachol did not modify membrane potential of the smooth muscle cells in either muscle tissue, yet these agents evoked muscle relaxation or contraction, respectively; in the sphincter muscle. Reversed sequences of mechanical responses were observed in the dilator. Ca-free solution reduced the resting tension and blocked the agonist-induced contraction in both muscle tissues. Excess-[K]0 solution dose-dependently depolarized the muscle membrane, and evoked combined mechanical responses of relaxation and contraction which were blocked by adrenergic and cholinergic blocking agents, mainly due to NE or acetylcholine (ACh) released from the nerve terminals in both muscle tissues. In the sphincter muscle, excess-[K]0 solution evoked a phasic contraction in the presence of these blocking agents. Specific mechanical features of the dog iris in relation to excitation-contraction coupling were given attention.

Adrenergic alpha-Antagonists↗
PubMed1985

Adrenergic excitatory and cholinergic inhibitory innervations in the human iris dilator.

To investigate the pattern of innervation in the human iris dilator muscle, effects of field stimulation on the isometric tension of dilator muscle were investigated in vitro. Throughout the experiments, spontaneous contractions did not occur. Application of repetitive field stimulations evoked biphasic mechanical responses (i.e. an initial phasic contraction followed by long lasting relaxation) of the isolated human iris dilator. These mechanical responses were abolished by 10(-7) M tetrodotoxin (a nerve poison), thereby indicating that the mechanical responses were neurogenic. Furthermore, the initial phasic contractions and following muscle relaxation were selectively blocked by phentolamine (10(-5) M) and atropine (10(-5) M), respectively. The degree of the muscle relaxation to that of contraction was much larger than that assumed by other investigators who used tissues from different species. The present results indicate that the human iris dilator muscle is innervated by adrenergic excitatory and cholinergic inhibitory nerves, and that cholinergic inhibitory innervations in this muscle may support the cholinergic miosis in the iris sphincter muscle.

Biomechanical Phenomena↗
PubMed1985

Effects of calcium antagonists on smooth muscle membranes of the canine stomach.

In circular muscles of the canine stomach, diltiazem (greater than 3 X 10(-6)M) depolarized and nicardipine (greater than 10(-6)M) hyperpolarized the membrane. Diltiazem (greater than 5 X 10(-6)M) or nicardipine (greater than 3 X 10(-7M) inhibited the plateau potential of spontaneously generated or electrically evoked action potential. In Na-deficient solution (between 137 and 30 mM Na), diltiazem and nicardipine selectively inhibited the plateau potential. In Na- (15 mM Na) or Ca-deficient (0.25 mM Ca) solution, spontaneously generated action potential ceased, and only graded responses were evoked by electrical stimulation. These graded responses were inhibited by diltiazem (greater than 5 X 10(-6)M) or nicardipine (greater than 3 X 10(-7)M). The ionic contribution for generation of action potential in this muscle cell was discussed in relation to actions of Ca antagonists.

Action Potentials↗
PubMed1984

Granular cell tumor of the lower lid: histological and immunohistochemical studies.

Histological and immunohistochemical studies of a granular cell tumor involving the lower lid are described. Histological examination showed it to have typical features of a granular cell tumor. Nervous-system-specific protein (S-100 protein) was detected in both the nuclei and cytoplasm of granular cells using the peroxidase-anti-peroxidase method. This result further supports the concept of the neurogenic origin of granular cell tumors.

Adult↗
PubMedDate not supplied

Adrenoceptors affect accommodation by modulating cholinergic activity.

In an attempt to clarify the functional role of adrenoceptors in accommodation, the effects of various adrenergic agents on the state of accommodation were studied. Fifty-two emmetropic, visually normal subjects (24.6 +/- 0.42 years old) participated in this study. Using an infrared optometer, the far and near points of accommodation were measured by a quasistatic method. Tonic accommodation and accommodative adaptation were also investigated. All these parameters were measured before and after topical application of various adrenergic agents. Both bunazosin hydrochloride (0.1%) and phenylephrine hydrochloride (5%) had no effect on tonic accommodation and accommodative adaptation. However, bunazosin hydrochloride increased the near point of accommodation. Timolol maleate (0.5%) and isoproterenol hydrochloride (3.0%) did not affect tonic accommodation. Isoproterenol hydrochloride evoked a hyperopic shift of the far point of accommodation by 0.23 +/- 0.42 diopters (D). Additionally, accommodative adaptation was increased by timolol maleate (0.36 +/- 0.62 D) and decreased by isoproterenol hydrochloride (0.18 +/- 0.48 D). These results indicate that both alpha and beta adrenoceptors affect accommodation. Activation of alpha adrenoceptors increased the near point of accommodation and activation of beta adrenoceptors decreased accommodative adaptation, which suggests that activation of adrenoceptors may modify parasympathetic activity; hence, affecting the state of accommodation.

Accommodation, Ocular↗
PubMedDate not supplied

Presynaptic effects of botulinum toxin type A on the neuronally evoked response of albino and pigmented rabbit iris sphincter and dilator muscles.

PURPOSE: To investigate the effects of botulinum toxin type A (botulinum A toxin) on the autonomic and other nonadrenergic, noncholinergic nerve terminals. METHODS: The effects of botulinum A toxin on twitch contractions evoked by electrical field stimulation (EFS) were studied in isolated albino and pigmented rabbit iris sphincter and dilator muscles using the isometric tension recording method. RESULTS: Botulinum A toxin inhibited the fast cholinergic and slow substance P-ergic component of the contraction evoked by EFS in the rabbit iris sphincter muscle without affecting the response to carbachol and substance P. These inhibitory effects were more marked in the albino rabbit than in the pigmented rabbit. Botulinum A toxin (150 nmol/L) did not affect the twitch contraction evoked by EFS in the rabbit iris dilator muscle. CONCLUSIONS: These data indicated that botulinum A toxin may inhibit not only the acetylcholine release in the cholinergic nerve terminals, but also substance P release from the trigeminal nerve terminals of the rabbit iris sphincter muscle. However, the neurotoxin has little effect on the adrenergic nerve terminals of the rabbit iris dilator muscle. Furthermore, the botulinum A toxin binding to the pigment melanin appears to influence the response quantitatively in the two types of irides.

Albinism↗