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Biomedical subjects

I Takayanagi

Publications and source records attributed to I Takayanagi.

At least 199 records · Page 11Linked to original sources
PubMed1985

Possible mechanisms of inhibitory action of sodium nitroprusside on histamine-induced contractile responses in isolated rabbit aorta compared with basilar artery and taenia coli.

Possible mechanisms of the inhibitory actions of sodium nitroprusside (NaNP) on histamine-induced contractile responses of isolated rabbit aorta, basilar artery and taenia coli were studied. NaNP (3 X 10(-5) M) reduced maximum contractile response to histamine in the aorta, whereas a concentration (10(-4) M) of NaNP slightly shifted the concentration-response curve for histamine towards its higher concentrations, but did not influence the maximum response in the basilar artery and taenia coli. The reduction in the maximum response of the aorta by NaNP was reversed by removal of the endothelium, or treatment with indomethacin (5 X 10(-6) M) or quinacrine (5 X 10(-6) M), but not by nordihydroguaiaretic acid (NDGA) (5 X 10(-5) M). Prostaglandin (PG) E1, PGE2 and PGI2 produced a relaxation in histamine-contracted basilar artery and taenia coli, whereas PGE1 and PGE2 produced a weak relaxation in histamine-contracted aorta. PGD2 relaxed taenia coli contracted by histamine, but had no influences in aorta and basilar artery. From these results, it is concluded that the inhibitory action of NaNP on histamine-induced contractile response in isolated rabbit aorta may be mediated at least partly by endothelium-derived arachidonic acid metabolite(s) via the cyclooxygenase pathway which must not involve PGI2. Furthermore, the difference in the inhibitory actions of NaNP between the tissues used in this study must be attributed to the absence of such mechanisms both in the basilar artery and taenia coli.

Animals↗
PubMed1985

A possible mechanism in interaction of a partial agonist with beta-adrenoceptor in guinea-pig taenia caecum: effects of Gpp(NH)p on its two different binding sites.

The mechanisms of the actions of the beta-adrenergic partial agonist (befunolol) were studied in isolated guinea-pig taenia caecum. Befunolol, 2-acetyl-7-(2-hydroxy-3-isopropylaminopropoxy)benzofuran hydrochloride was found to be a typical partial agonist in guinea-pig taenia caecum. The pD2-value of befunolol was in agreement with its pKA-value obtained with photoaffinity labeling, but was different from its pA2-value against isoprenaline and pKI-value obtained from the inhibition of specific [3H]-dihydroalprenolol binding. The Scatchard plot of the specific [3H]-befunolol binding showed two affinity sites of the receptor in the absence of Gpp(NH)p, but the low affinity site was reduced while the high affinity site was not affected in the presence of Gpp(NH)p. The pKD-value of the high affinity site of befunolol was in agreement with its pA2-value, and the pKD-value of the low affinity site was in agreement with its pD2-value or pKA-value. These results suggest that the beta-adrenergic partial agonist may interact with two different sites: an agonist binding site and an antagonist binding site.

Adrenergic beta-Agonists↗
PubMed1985

Muscarinic acetylcholine receptors in the rabbit ciliary body smooth muscle: spare receptors and threshold phenomenon.

Interactions of several muscarinic drugs with their receptors were studied in the ciliary body smooth muscles of the rabbit. The ciliary body smooth muscles responded to carbachol, a muscarinic full agonist, with concentration-dependent contractions, and the pD2 value of carbachol was 5.16 +/- 0.05. Atropine, a competitive antagonist of muscarinic receptors, produced a parallel shift to the right in the concentration-response curves for carbachol. Pilocarpine which is a well-known partial agonist on muscarinic receptors in most smooth muscles did not cause any contraction in this tissue. The drug, however, behaved as a competitive antagonist on the muscarinic receptors in the ciliary body smooth muscles. The pA2 values of atropine and pilocarpine versus carbachol obtained from the Schild plot are 8.97 +/- 0.25 and 5.17 +/- 0.09, respectively. On the other hand, arecoline and oxotremorine acted as a partial agonist in this tissue. The intrinsic activity, and pD2 and pA2 values were 0.41 +/- 0.02, 4.93 +/- 0.05 and 5.32 +/- 0.05 for arecoline respectively, and were 0.26 +/- 0.02, 5.64 +/- 0.08 and 6.12 +/- 0.16 for oxotremorine, respectively. The pA2 values of these drugs were significantly larger than the corresponding pD2 values of the drugs. The values of the negative log molar dissociation constant of carbachol, arecoline and oxotremorine estimated by the method of partial irreversible blockade of spare receptors with 3 X 10(-6) M phenoxybenzamine were 4.53 +/- 0.08, 5.20 +/- 0.09 and 6.02 +/- 0.06, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The stimulative effect of sodium on the depletion process of calcium in the intracellular store of smooth muscle cells of guinea-pig taenia caecum.

The effect of readmitted Na on the Ca-depletion process in the carbachol-sensitive Ca-store was investigated using thin bundles of the K-depolarized, Na-depleted guinea-pig taenia caecum. To estimate the quantity of stored Ca, the "Ca-load Ca-release" method was employed: To load the store with Ca, 2 mM Ca was added and left (phase A), and then it was removed by washing with 2 mM EGTA-containing solution (phase B); 10(-3) M carbachol was then applied (phase C). Instead of glucose, pyruvate was used as a nutrient. Millimolar concentrations of Na inhibited the carbachol-induced contractions when Na was present during phase B. Na present during phase A also reduced the carbachol-induced contraction, but not when Na was treated during phase C. As the period of phase B was prolonged, the carbachol-induced contraction was reduced, which suggests the depletion process of stored Ca resulting from extrusion of Ca from the cell. Na present during phase B accerelated the rate of the Ca-depletion process. Li mimicked Na with regard to the promoting effect on the depletion process, and the effect of Na was not affected by 10(-4) M ouabain, suggesting that Na-Ca exchange would not be involved in the effect of Na. These results suggest that Na may be involved in the maintenance of cellular Ca-homeostasis through the stimulation of efflux of Ca from the store to the outside of the cell.

Animals↗
PubMed1985

Do D 600 and diltiazem interact with serotonin receptors in rabbit vascular tissues?

This study investigates the interactive effects of Ca antagonists and responses to serotonin (5-HT) in isolated rabbit aorta and basilar artery. Isolated strips of rabbit aorta and of basilar artery were studied in organ baths containing 20 ml of Krebs-buffer solution. D 600 or diltiazem caused parallel rightward shifts of concentration-response curves for 5-HT in isolated rabbit aorta, but each reduced the 5-HT-induced maximum response in basilar artery. The slope values from Schild plot analyses in aorta were 1.11 +/- 0.05 and 1.22 +/- 0.37 in D 600 and diltiazem, respectively. Dibenamine pretreatment caused reduction of maximum response to 5-HT in both tissues. Such reduction was diminished markedly by the presence of D 600, diltiazem or 5-HT in aorta but not in basilar artery. Also, the antagonistic effects of D 600 and diltiazem were diminished by elevation of bath Ca in basilar artery but not in aorta. These results strongly suggest that the two Ca entry blockers used in this study might compete with 5-HT at 5-HT receptors in rabbit aorta and that the pharmacomechanical property of 5-HT receptors in rabbit aorta might be distinct from that in rabbit basilar artery.

Animals↗
PubMed1984

Tetrodotoxin-resistant response to nicotine in rabbit bronchial preparation.

The mode of action of nicotine was studied in a rabbit bronchial preparation. Nicotine (3 X 10(-5)-10(-3) M) produced a phasic contraction. No inhibitory response to nicotine was observed. The contractile response to nicotine was inhibited by hexamethonium, pentolinium and atropine but not by tetrodotoxin. Nicotine increased the efflux of tritium from preparations which had been labelled with [3H]choline. Tetrodotoxin did not inhibit the nicotine-evoked tritium release from the bronchial preparation. The results indicate that the release of acetylcholine evoked by nicotine was not influenced by tetrodotoxin in this preparation, and that the nicotine-induced response may be produced mainly through a sodium action potential-independent process. We could not rule out a contribution by acetylcholine released from the acetylcholine store in the smooth muscle in the contractile mechanisms for nicotine.

Acetylcholine↗
PubMed1984

Intrinsic activity and effects of guanyl-5'-yl imidodiphosphate, Gpp(NH)p on the affinity of partial agonists to the muscarinic receptor.

The effects of a GTP analogue, guanyl-5'-yl imidodiphosphate, Gpp(NH)p on the inhibition of [3H]3-quinuclidinyl benzilate (QNB) binding by some partial agonists were studied with a microsomal fraction of longitudinal muscle of guinea-pig ileum and compared with the intrinsic activity of the partial agonists which was estimated in the longitudinal muscle of guinea-pig ileum. There was a good correlation between the inhibitory effects of Gpp(NH)p on the affinity of the partial agonists to muscarinic receptors and their intrinsic activity.

Animals↗
PubMed1984

Effect of clenbuterol, a new beta 2 selective adrenoceptor stimulant, on the release of histamine and SRS-A from passively sensitized guinea-pig chopped lungs.

Effect of clenbuterol on the release of histamine and SRS-A from passively sensitized guinea-pig lungs was studied in a superfused-cascade bioassay system, and compared with isoproterenol and salbutamol. One-week-old guinea-pig lungs were used, since histamine and SRS-A were released more in these than in 6- or 12-week old lungs during anaphylaxis. Clenbuterol, isoproterenol and salbutamol (10(-8) - 10(-7) M) were found to inhibit the releases of histamine and SRS-A. These actions were inhibited by propranolol. These results suggest that clenbuterol inhibits the releases of histamine and SRS-A via the beta-adrenoceptor.

Aging↗
PubMed1984

Action of nicotine on guinea-pig isolated bronchial smooth muscle preparation.

In the isolated bronchial preparation of the guinea-pig, nicotine induced a contraction but not a relaxation. The contractile response of the bronchial preparation to nicotine was inhibited by hexamethonium and d-tubocurarine but not influenced by atropine and tetrodotoxin. In the isolated tracheal preparation of the guinea-pig where nicotine stimulated nicotinic receptor in nervous tissues, the contractile response to nicotine as considerably accelerated by the treatment of the guinea-pig with egg-albumin, while the contractile response of the bronchial preparation to nicotine was not influenced by the same treatment. These results suggest that a possible site of action of nicotine in the isolated bronchial preparation is not on the nervous cells but on the smooth muscle cells. However, we could not rule out a contribution by chemical mediators released by nicotine in the contractile mechanisms in the bronchial preparation.

Airway Resistance↗
PubMed1984

Interaction of a beta-adrenergic partial agonist with its receptor in guinea-pig taenia caecum.

Beta-adrenoceptor mechanisms in guinea-pig taenia caecum were studied by means of a receptor-binding technique. Hill plots of test drugs obtained from inhibition curves were linear with slopes which were equal to 1.00. pKi-values of isoprenaline and desisopropylprocaterol were in agreement with those pD2-values. pKi-value of carteolol was in agreement with its pA2-value. The beta-adrenoceptor is suggested to have two different sites; one can interact with the agonist and partial agonist and the other can interact with the antagonist and partial agonist.

Adrenergic beta-Agonists↗
PubMed1984

Nicotinic stimulant, DMPP(1,1-dimethyl-4-phenylpiperazinium iodide) on the isolated bronchial smooth muscle preparation of guinea-pig.

Contractile responses of the isolated bronchial preparation of guinea-pig to DMPP, a nicotinic stimulant, were inhibited by ganglion blockers but not influenced by atropine, suggesting that DMPP did not bring about a contribution by stimulation of cholinergic ganglion cells. The fact that tetrodotoxin did not influence the response to DMPP suggests that a possible site of action of DMPP is not on the nerve cells.

Animals↗
PubMed1984

Interaction of morphine-epoxide with multiple opiate receptors.

We examined the interaction of morphine-epoxide, which was assumed to be a new metabolite of morphine, with opiate receptor subtypes using pharmacological and biochemical techniques. Morphine-epoxide was about 3 to 4 times less potent than morphine to the interactions of opiate receptors. However, the ratio of IC50 values for the guinea pig ileum and mouse vas deferens to electrical field stimulation and the ratio of IC50 values for the [3H]-dihydromorphine and [3H]-D-ala2-D-leu5 enkephalin binding to rat brain membrane preparations of morphine-epoxide was similar to those of morphine. Morphine-epoxide had virtually no effect on the twitch responses of rabbit and rat vas deferens. Furthermore, "sodium ratio" and "GTP ratio" of morphine-epoxide were similar to those of morphine and differed from naloxone. These results suggest that morphine-epoxide as well as morphine behaves as the agonist on the mu type opiate receptor notwithstanding that the affinity of morphine-epoxide is slightly less than that of morphine.

Analgesics↗
PubMed1984

Effects of morphine, clonidine and papaverine on synaptosomal 45Ca uptake and antinociceptive action in rats.

We studied the relationship between the inhibition of extracellular 45Ca2+ uptake into synaptosomes and the antinociceptive action induced by morphine, clonidine and papaverine in rats. The antinociceptive action induced by clonidine was as potent as that by morphine, but that by papaverine was less potent than those by morphine and clonidine. Antinociceptive action by morphine was considerably potentiated by the simultaneous administration of clonidine. However, the antinociceptive actions induced by morphine and clonidine were found to be mediated through different receptor mechanisms. Although the pretreatment by papaverine blocked the morphine-induced antinociception, the inhibition induced by papaverine was not found to be mediated through the opiate receptor because papaverine did not displace [3H]-dihydromorphine binding to the membrane fraction from rat brain. Papaverine also inhibited the antinociceptive action induced by clonidine. Morphine inhibited the veratrine-stimulated synaptosomal 45Ca2+ uptake by a naloxone-reversible process. Papaverine also strongly inhibited the veratrine-stimulated synaptosomal 45Ca2+ uptake, while clonidine had virtually no effect. The inhibition of synaptosomal 45Ca2+ uptake induced by morphine was not increased by simultaneous addition of clonidine. The strong inhibitions of synaptosomal 45Ca2+ uptake were still observed by simultaneous addition of papaverine with morphine and clonidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1984

Interactions of some partial agonists with beta-adrenoceptor in the isolated taenia caecum and tracheal smooth muscle of guinea pig.

The indexes for agonistic activity (pD2 values) and for antagonistic activity (pA2 values) of some beta-adrenergic partial agonists were estimated in the isolated taenia caecum and tracheal preparation of guinea pig. The pK1 values, negative log of dissociation constants, were also estimated by photoinactivation of the beta-adreneoceptor in the taenia caecum. The pD2 values of the partial agonists were significantly different from their pA2 values, but equal to their pK1 values. If the partial agonists interacted with one site in their receptor, the pD2 values would be equal to the pA2 values because the partial agonists had little receptor reserve. These results suggest that the properties of the binding site for agonistic action were different from those for antagonistic action.

Adrenergic beta-Agonists↗
PubMed1983

Effects of cyclic AMP and protein kinase on calcium uptake in a microsomal fraction from guinea pig taenia caecum.

A microsomal fraction was isolated from guinea pig taenia caecum by differential centrifugation. Activities of ouabain-sensitive (Na+, K+)-ATPase, 5'-nucleotidase and NADPH-cytochrome c reductase were enriched in the microsomal fraction. On the other hand, less cytochrome c oxidase and monoamine oxidase were contained in this fraction. These results suggest that the microsomal fraction used in this study was derived from both sarcolemma and sarcoplasmic reticulum. Ca2+ uptake by this fraction was strictly dependent on the presence of ATP and was facilitated by oxalate. An ATP-regenerating system was required for the determination of Ca2+ uptake, when a lower concentration of ATP (e.g. 0.25 mM) was used. Phosphorylation of the microsomal fraction was doubled when these membranes were incubated in the presence of cyclic AMP plus cyclic AMP-dependent protein kinase (protein kinase). When the microsomal fraction was pretreated with cyclic AMP plus protein kinase, Ca2+ uptake was stimulated. The increases in microsomal phosphorylation and Ca2+ uptake were significantly correlated (P less than 0.01). This stimulation of Ca2+ uptake by microsomal phosphorylation was observed only in the presence of protein kinase, oxalate, and low Ca2+ and Mg2+ concentrations. The results suggest that stimulation of Ca2+ uptake may be the mechanism by which cyclic AMP is involved in beta-adrenergic relaxation of smooth muscle.

Adenosine Triphosphate↗