Biomedical subjects

K Koike

Publications and source records attributed to K Koike.

At least 523 records · Page 29Linked to original sources

PubMed1991

Interactions of N-cyclopropylmethyl(-)-6 beta-acetylthionormorphine with mu-, kappa-, delta- and sigma-opioid receptors.

1. Affinities of N-cyclopropylmethyl(-)-6 beta-acetylthionormorphine (KT-90) to mu-, kappa-, delta- and sigma-receptors were tested in rat brain membrane fractions using radioligand-receptor assays. 2. Though KT-90 had nonselectively high affinities to mu-, kappa- and delta-receptors, affinity of KT-90 to sigma-receptors was lower than those to the other three receptors. 3. Affinity of KT-90 to sigma-receptors was 1000 times lower than that of buprenorphine.

Animals↗

PubMed1991

Effects of aging on postsynaptic alpha 1-adrenoceptor mechanisms in rat aorta.

1. Effects of aging on alpha 1-adrenoceptor and S2-serotonin receptor mechanisms in rat aorta were studied. 2. In rat aorta, the potency (pD2 value) of norepinephrine or phenylephrine increased with age from 3 to 10 weeks, but decreased thereafter with age from 10 to 80 weeks. The affinity (pKA value) of norepinephrine or phenylephrine and of prazosin (pA2 value) did not alter with aging. 3. In rat vas deferens, the efficacy of norepinephrine and the maximum binding sites of [3H]prazosin increased with age from 3 to 18 weeks, but decreased thereafter with age from 18 to 60 weeks. The affinity (pKA value) of norepinephrine and the dissociation constant (KD value) of prazosin did not alter with aging. 4. In rat aorta, the potency (pD2 value) and affinity (pKA value) of serotonin, and affinity (pA2 value) of ketanserin did not alter with aging. 5. There is no significant difference between slopes of regression lines between a cytosolic free Ca2+ level [( Ca2+]i) and tension in the presence of phenylephrine in aorta strips from 10- and 60-week-old rats. 6. These results suggest that changes in alpha 1-adrenoceptor mechanisms with aging are due to changes in receptor density or receptor reserve, but not to changes in affinity of drugs to alpha 1-adrenoceptor or sensitivity of contractile system to Ca2+ mediated through alpha 1-adrenoceptor, and that S2-serotonin receptor mechanisms in rat aorta do not alter with aging.

Aging↗

PubMed1991

Vascular smooth muscle relaxation by alpha 1-adrenoceptor blocking action of denopamine in isolated rabbit aorta.

We investigated the mechanism of vascular relaxation by denopamine (Deno), an oral positive inotropic agent that has selective beta 1-adrenergic action. Deno relaxed, dose-dependently (0.1-30 microM), ring segments of rabbit aorta, which were partially precontracted with 1 microM phenylephrine (Phe) or norepinephrine (NE), but did not relax those precontracted with 5 microM prostaglandin F2 alpha or 40 mM K+. The relaxation was not significantly inhibited by pretreatment with 10 microM propranolol or metoprolol. Deno produced parallel shifts in concentration-response curves to Phe, but this was not true for clonidine. The Schild plot analysis resulted in a linear regression of a slope of 1.075 +/- 0.063, which was not significantly different from unity, and the pA2 value of Deno against Phe was 5.57 +/- 0.02. The specific binding of [3H]prazosin to a rabbit aorta membrane preparation was displaced in a concentration-dependent manner by the simultaneous addition of Deno. The slope of a Hill plot was not significantly different from unity (1.102 +/- 0.147). The pK1 value for Deno calculated from the displacement curve was 5.29 +/- 0.17, which was not significantly different from the pA2 value of Deno. In conclusion, vascular smooth muscle relaxation by Deno was mediated by the blocking effect of alpha 1-adrenoceptors. Thus, these findings suggest that Deno may be effective in the treatment of congestive heart failure because it elicits a positive inotropic effect by beta 1-adrenergic action and vasodilation by alpha 1-adrenergic blocking action.

Adrenergic alpha-Antagonists↗

PubMed1991

Platelet aggregation induced by adenosine diphosphate released from cloned murine fibrosarcoma cells is positively correlated with the experimental metastatic potential of the cells.

We established five clones (ML-01, ML-02, MH-01, MH-02, MH-03) from murine 3-methylcholanthrene-induced fibrosarcoma A (Meth A), and investigated their experimental metastatic potentials in relation to their platelet-aggregating activities. A clone with a high metastatic potential (MH-02) showed a characteristic biphasic pattern of platelet aggregation, of which the first peak was not present in the aggregation patterns of the clone with low metastatic potential (ML-01). The first peak was eliminated by treatment of the cells with apyrase, indicating that adenosine diphosphate (ADP) was the causative substance of this particular peak. The metastatic potential of clones correlated well with the ADP concentration of the culture media. These results suggest that the increased ADP production and consequential enhancement of platelet-aggregating activity are closely related to the increment of pulmonary metastatic potential of MH-02 clone.

Animals↗

PubMed1991

Induction of granulocyte and granulocyte-macrophage colony-stimulating factors from human monocytes stimulated by Fc fragments of human IgG.

The effect of human IgG on human haemopoiesis has been studied in vitro. Dialysed purified IgG stimulated haemopoietic colony growth by bone marrow mononuclear cells (MNC) but not by monocyte-depleted MNC. Culture media, conditioned by IgG-stimulated peripheral blood MNC, augmented formation of neutrophil-macrophage, eosinophil, and megakaryocyte colonies by monocyte-depleted marrow MNC. Serum-free IgG-conditioned media also contained colony-stimulating activity (CSA). IgG Fc fragments and heat-aggregated IgG promoted the secretion of CSA, but F(ab')2 fragments, Fab fragments or ultracentrifuged IgG did not. In the cell-selection studies, CSA was produced by highly enriched monocytes following stimulation with Fc fragments. The antiserum against human granulocyte colony-stimulating factor (G-CSF) and/or granulocyte-macrophage CSF (GM-CSF) neutralized the CSA produced by Fc fragment-activated monocytes. Enzyme immunoassays showed G-CSF and GM-CSF in media conditioned by monocytes stimulated with the Fc fragments, heat-aggregated IgG and anti-D-sensitized red blood cells (RBC). Northern hybridization analysis showed mRNA encoding G-CSF and GM-CSF in RNA extracted from MNC and monocytes cultured with the Fc fragments, but not in the RNA from unstimulated cells or monocyte-depleted MNC. These results indicate that IgG Fc fragments, aggregated IgG and antigen-antibody complexes induce monocytes to produce G-CSF and GM-CSF in vitro. The CSFs release induced by IgG may be involved in the in vivo regulatory network in haemopoiesis.

Cell Division↗

PubMed1991

Prevalence of virulent Rhodococcus equi in isolates from soil and feces of horses from horse-breeding farms with and without endemic infections.

The prevalence of virulent Rhodococcus equi in isolates from soil and feces of foals on a farm with endemic R. equi infections was significantly higher than that of a farm with no history of the disease. Foals bred on a farm with the endemic disease might be constantly exposed to virulent R. equi in their environment.

Actinomycetales Infections↗

PubMed1991

Identification of 15- to 17-kilodalton antigens associated with virulent Rhodococcus equi.

Antigens of Rhodococcus equi were analyzed by immunoblotting with naturally infected foal sera. Immunoblots of whole-cell antigen preparations of clinical isolates of R. equi revealed that major protein bands with molecular masses of 15 to 17 kDa were present in all clinical isolates tested and all isolates virulent for mice. In contrast, the 15- to 17-kDa antigens were not identified by immunoblotting in ATCC 6939, a type strain of R. equi that was avirulent for mice. Whole-cell antigens of 102 environmental isolates were investigated by immunoblotting and the mouse pathogenicity test. Twenty-five of these isolates were demonstrated to contain the 15- to 17-kDa antigens by immunoblotting and were virulent for mice. The remaining 77 environmental isolates lacked the 15- to 17-kDa antigens and were avirulent for mice. These data suggest that the diffuse 15- to 17-kDa proteins are virulence-associated antigens with immunogenicity in foals and that they may be useful in marking virulent R. equi contamination in the environment of a horse-breeding farm.

Actinomycetales Infections↗

PubMed1991

Comparison of interactions of R-(+)- and S-(-)-isomers of beta-adrenergic partial agonists, befunolol and carteolol, with high affinity site of beta-adrenoceptors in isolated rabbit ciliary body and guinea-pig taenia caeci.

The stereoselectivities of beta-adrenergic partial agonists for the high affinity binding site of beta-adrenoceptors in the rabbit ciliary body and the guinea-pig taenia caeci were studied. The pA2 values of the S-(-)-isomers of befunolol and carteolol against S-(-)-isoprenaline, which were calculated from the shift of each concentration - response curve in increasing cyclic AMP levels, were significantly larger than those of the R-(+)-isomers in the guinea-pig taenia caeci, while the pA2 values of the S-(-)-isomers were not significantly larger than those of the R-(+)-isomers in the rabbit ciliary body. The pK1 values determined from the binding experiments were in good agreement with the pA2 values from the increases in cyclic AMP levels. These results suggest that the high affinity binding site of beta-adrenoceptors in the guinea-pig taenia caeci may be able to discriminate stereoselectively between the R-(+)- and S-(-)-isomers, while in the rabbit ciliary body there is no stereo-selectivity between the two enantiomers.

Adrenergic beta-Antagonists↗

PubMed1991

Effects of the R(+)- and S(-)-isomers of beta-adrenoceptor blockers with intrinsic sympathomimetic activity, befunolol and carteolol, on rabbit intraocular pressure.

Effects of the R(+)- and S(-)-isomers of befunolol and carteolol, beta-adrenoceptors with intrinsic sympathomimetic activity, on the rabbit intraocular pressure were tested. The intraocular pressure was decreased by instillation of the R(+)- and S(-)-isomers of befunolol (0.1 and 0.3%) and of carteolol (1.0%) to the eye and attained the minimum level at 60 min. However, 0.3% of the R(+)- and S(-)-isomers of carteolol did not influence the pressure. The corresponding time courses for the intraocular pressure for the R(+)- and S(-)-isomers did not differ, suggesting that in the treatment of glaucoma, the therapeutic advantage of the R(+)-isomers of befunolol and carteolol may be similar to the S(-)-isomers.

Adrenergic beta-Antagonists↗

PubMed1991

Differences in alpha 1-adrenoceptor mechanisms for phenylephrine and tizanidine in rabbit thoracic aorta and common iliac artery.

Based on affinity for WB4101 and susceptibility to chloroethylclonidine, we evaluated the subtype of alpha 1-adrenoceptors activated by phenylephrine (a full agonist) and tizanidine (a partial agonist). The rabbit thoracic aorta and common iliac artery contain both alpha 1A- and alpha 1B-adrenoceptors, but the alpha 1B-subtype may be more predominantly in the common iliac artery than in the thoracic aorta. In rabbit thoracic aorta and common iliac artery, phenylephrine induced contraction through both alpha 1A- and alpha 1B-subtypes and tizanidine through only the alpha 1A-subtype. The subtype activated by phenylephrine may be partly different from that activated by tizanidine in the preparations used herein.

Animals↗

PubMed1991

Interleukin-6 stimulates gonadotropin-releasing hormone secretion from rat hypothalamic cells.

There are reports that both interleukin-1 beta and interleukin-6 (IL-6) stimulate the release of adrenocorticotropin through stimulation of hypothalamic corticotropin-releasing factor. We established a primary culture system for hypothalamic neurons producing gonadotropin-releasing hormone (GnRH) and examined whether IL-6 stimulated their GnRH secretion. We demonstrated immunohistochemically that some of these neurons contained GnRH-like immunoreactivity. In primary cultures of these GnRH neurons, we found that the calcium ionophore A23187 stimulated GnRH secretion in a dose- and time-dependent manner. These hypothalamic cells secreted IL-6 spontaneously, producing about 10 ng/l in 24 h, and their IL-6 secretion was significantly stimulated by E2 at 10(-9)-10(-8) mol/l. This stimulatory effect was observed within 3 h. IL-6 also stimulated the release of GnRH in a dose- and time-dependent manner, and these effects of IL-6 were significantly blocked by anti-IL-6 antiserum. These results suggest that the central action of IL-6 on the GnRH neurons may be an important physiological event in the hypothalamus.

Animals↗

PubMed1991

Effect of prolactin on the secretion of hypothalamic GnRH and pituitary gonadotropins.

In order to clarify the mechanism by which excess PRL inhibits gonadotropin release, in vivo and in vitro studies were performed with adult female rats. First, we examined the effect of hyperprolactinemia, produced by implantation of anterior pituitary glands under the kidney capsule, on catecholamine turnover in the medial basal hypothalamus (MBH) and on GnRH concentrations in MBH and hypophyseal portal blood. Rats bearing pituitary transplants exhibited increased turnovers of dopamine (DA) in the MBH, decreased concentrations of GnRH in the MBH and in plasma of hypophyseal portal blood and impaired gonadotropin release from the pituitary gland. Second, we examined the effects of PRL on DA release and of DA on GnRH release from rat hypothalamic cells. We observed that PRL stimulated [3H] DA release, and DA inhibited ionophore-induced GnRH release from dispersed hypothalamic cells. Third, we examined the effect of PRL on estrogen-induced LH release using the in vitro perfusion system. We found that administration of PRL suppressed estrogen-induced LH release by suppressing GnRH release from the hypothalamus. These findings suggest that chronic hyperprolactinemia may increase dopaminergic tone in the MBH that may inhibit GnRH secretion from the MBH and LH release from the pituitary and that these processes may be responsible for disturbances of cyclic hypothalamic pituitary-ovarian activity.

Animals↗

PubMed1991

Tumor necrosis factor-alpha stimulates prolactin release from anterior pituitary cells: a possible involvement of intracellular calcium mobilization.

We investigated the effects of tumor necrosis factor-alpha (TNF alpha), a cytokine produced as one aspect of inflammatory reactions, on the intracellular free calcium concentration in single pituitary cells using a calcium-sensitive fluorescent dye, indo-1, and a digital imaging fluorescence microscopic system. TNF alpha induced an increase in intracellular free calcium immediately after administration, reaching a peak after 30 sec and then returning to nearly the basal level after 120 sec in the pituitary cells. The cells responding to TNF alpha constitute about 15% of the pituitary cell population, and these cells never responded to the hypothalamic releasing hormones TRH, GnRH, GH-releasing hormone, or CRH. To define the role of calcium in TNF alpha-induced PRL release, dispersed pituitary cells were exposed to agents that modify TNF alpha-induced calcium mobilization. Such calcium channel blockers as cobalt and verapamil decreased basal and TNF alpha-induced PRL release. A low calcium medium also decreased TNF alpha-induced PRL release. These data suggest that intracellular calcium mobilization may be involved in the process of TNF alpha-induced PRL release.

Animals↗

PubMed1991

Tumor necrosis factor-alpha increases release of arachidonate and prolactin from rat anterior pituitary cells.

We investigated the effect of tumor necrosis factor-alpha (TNF alpha), a product of activated macrophages, on the release of arachidonate from dispersed anterior pituitary cells. Primary cultures of anterior pituitary cells from rats were preincubated with [3H]arachidonate to label their phospholipid-containing components. The cells were then washed and incubated with vehicle or test agents, and PRL release into the medium and [3H]arachidonate cleaved from phospholipid were measured. TNF alpha significantly increased the release of both PRL and [3H] arachidonate release in a time- and dose-dependent manner. Other cytokines, such as interleukin-1 alpha, interleukin-1 beta, and gamma-interferon, had no effect on [3H]arachidonate release. To define the role of calcium in TNF alpha-induced arachidonate release, dispersed pituitary cells were incubated with low calcium medium, which decreased arachidonate release in response to TNF alpha. TNF alpha potentiated the release of [3H]arachidonate and PRL promoted by phospholipase-A2 and melittin, and markedly shifted the dose-response curve to the left. Inhibitors of phospholipase-A2, such as p-bromophenacyl bromide and quinacrine, had no effect on TNF alpha-induced [3H]arachidonate and PRL release. BW755C, an inhibitor of the conversion of arachidonate to its metabolites, decreased TNF alpha-induced PRL release, while indomethacin, a prostaglandin synthesis inhibitor, had no effect on TNF alpha-induced PRL release. These data indicate that arachidonate metabolites may be involved in the process of TNF alpha-induced PRL release.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1991

Variation in sensitivity of alpha 1-adrenoceptor stimulants and alpha 1-adrenoceptor mechanisms in rabbit arteries.

Sensitivity (pD2 value, negative logarithm of the molar concentration producing the half maximum response) and affinity (pKA value, negative logarithm of dissociation constant) of norepinephrine were determined in 6 arteries from rabbits. A positive correlation was found in the pD2 and pKA values of norepinephrine. The slope was not significantly different from 1. The pD2 and pKP (a negative logarithm of dissociation constant of a partial agonist) values of tizanidine, an alpha 1-partial agonist, were also determined. There were positive correlations between the pD2 and pKP values of tizanidine and also between the two pD2 values of norepinephrine and tizanidine. The slopes were not significantly different from 1. These results suggest that the regional differences in pD2 values of norepinephrine and tizanidine in the arteries are partly due to the affinity and suggest that both drugs interact with one recognition site in the alpha 1-adrenoceptors. The dissociation constants, KD values, and the maximum binding sites, Bmax, for [125I]-HEAT were also estimated by Scatchard analysis of the specific binding of [125I]-HEAT to the membrane fractions from rabbit arteries. The KD values for [125I]-HEAT were also identical. However, Bmax varied considerably among rabbit arteries. There was a positive correlation between the logarithm of Bmax and the pD2 values for norepinephrine. The present results suggest that the regional difference in the pD2 values for norepinephrine in rabbit arteries is due to variations in the affinities to the alpha 1-adrenoceptors as well as the receptor densities.

Adrenergic alpha-Agonists↗

PubMed1991

Propylbenzilycholine mustard (PrBCM)-sensitive cholinoceptors and contractile response to partial agonist in guinea pig ileal muscle.

Pilocarpine, a partial agonist, activates propylbenzilylcholine mustard (PrBCM)-sensitive cholinoceptors in the guinea pig ileal longitudinal muscle, while carbachol, a full agonist, predominantly activates PrBCM-resistant ones. Carbachol behaves as a partial agonist in the preparation treated with phenoxybenzamine and mainly activates PrBCM-sensitive cholinoceptors, as phenoxybenzamine preferably blocks PrBCM-resistant ones. The receptor occupancy-response curve for carbachol became a rectangular hyperbola, while pilocarpine showed a linear relation. After occlusion of cholinoceptors with phenoxybenzamine, carbachol showed a linear receptor occupancy-response relation, suggesting that its contraction mechanisms after occlusion of cholinoceptors resemble those for pilocarpine. Both the agonists induced an increase in cytosolic Ca2+ concentration [( Ca2+]i) and tension development in a concentration-dependent manner under the conditions used herein. The slopes of the regression lines between [Ca2+]i and tension development for pilocarpine in the untreated preparation and for carbachol in the preparation treated with phenoxybenzamine were significantly steeper than that for carbachol in the untreated preparation, suggesting that carbachol in the phenoxybenzamine-treated preparation and pilocarpine induced a greater tension for a given increase in low [Ca2+]i than did carbachol. Thus an activation of PrBCM-sensitive cholinoceptors might enhance the Ca2+-sensitivity of the contractile elements.

Algorithms↗

PubMed1991

A difference in receptor mechanisms for muscarinic full and partial agonists.

Concentration-response curves of 4 muscarinic full agonists were progressively inhibited by 10 to 50-min treatments of the longitudinal muscle of guinea pig ileum with propylbenzilylcholine mustard (PrBCM, 3 x 10(-6) M). A 90-min treatment with PrBCM had no further significant inhibitory effect on their curves. The 50-min treatment with PrBCM (3 x 10(-6) M) completely inhibited the concentration-response curves of 6 partial agonists. The limiting effect of PrBCM observed on the concentration-response curves of the full agonists was not found on the curves of the partial agonists. These results suggest that there are two subtypes of M3-cholinoceptors, PrBCM-sensitive receptors and PrBCM-resistant ones. Pilocarpine, a partial agonist, shifted the concentration-response curve of carbachol, a full agonist, in a parallel fashion in the strips treated with PrBCM (3 x 10(-6) M) for 50 min, suggesting that an interaction of pilocarpine with PrBCM-resistant cholinoceptors does not induce contraction. The full agonists contract the longitudinal muscle through the interaction of two cholinoceptors, PrBCM-sensitive and -resistant ones, while the partial agonists produce the contraction through the activation of PrBCM-sensitive ones.

Animals↗

PubMed1991

Effect of TNF-alpha on prolactin secretion from rat anterior pituitary and dopamine release from the hypothalamus: comparison with the effect of interleukin-1 beta.

The effects of human recombinant interleukin-1 beta and -6 and tumor necrosis factor-alpha (TNF-alpha) on the releases of PRL and dopamine were examined using monolayer cultures of rat pituitary cells and hypothalamic cells. The release of PRL from rat pituitary cells in 30 min was increased about 2-fold (p less than 0.05) by 10(5) U/l interleukin-1 beta, 10(5) U/l interleukin-6 or 100 micrograms/l TNF-alpha. TNF-alpha at 100 micrograms/l significantly increased PRL release within 5 min incubation and this effect continued throughout the next 30 min of incubation. Incubation for 5 min with TNF-alpha caused dose-dependent stimulation of PRL release. These cytokines did not modulate [3H]-dopamine release from primary cultures of hypothalamic cells. These results suggest that these cytokines stimulate PRL release directly at the pituitary gland, without modifying the release of dopamine from the hypothalamus.

Animals↗