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Biomedical subjects

I Takayanagi

Publications and source records attributed to I Takayanagi.

At least 145 records · Page 8Linked to original sources
PubMed1988

Ryanodine: its possible mechanism of action in the caffeine-sensitive calcium store of smooth muscle.

The caffeine-sensitive intracellular Ca store was characterized and the mechanism of action of ryanodine in the store was studied using K-depolarized guinea-pig taenia caecum. (1) After incubation of the preparation with CaCl2 (Ca loading), caffeine was applied in Ca-deprived medium, to produce a transient contraction and to monitor the amount of the stored Ca. As duration of Ca deprivation was prolonged, the amplitude of the caffeine-induced contraction was decreased. When ryanodine was applied during Ca deprivation, the rate of the decrease was remarkably accelerated. (2) The rate of rise of the contraction induced by external Ca [Ca)o) was slowed by preceding depletion of the stored Ca by caffeine, compared with that observed in the Ca loaded preparation. However, in the presence of ryanodine, even if stored Ca was depleted by caffeine, the rate of rise of the (Ca)o-induced contraction remained at a higher level. (3) These results suggest that ryanodine stimulates a leak of the stored Ca, and that the contraction induced by the transmembrane influxed Ca could be modulated by the amount of Ca in, or leakiness of, the caffeine-sensitive Ca store.

Alkaloids↗
PubMed1988

Pharmacological properties of a new centrally acting muscle relaxant (NC-1200) in isolated muscle preparations.

1. Pharmacological properties of a new centrally acting muscle relaxant (NC-1200) were tested in isolated muscle preparations. 2. NC-1200 acted as a Ca-blocker in the guinea pig taenia caecum. The pA2-value was 5.67. 3. In the rabbit aorta, NC-1200 competed with serotonin at serotonin receptors and also shifted the concentration response curves of histamine and norepinephrine suggesting the possibility that NC-1200 interacted with histamine and norepinephrine receptors. The pA2-value of NC-1200 against serotonin was 6.02. 4. There was no evidence that NC-1200 interacted with drug-receptors in the muscles except the rabbit aorta. 5. The present results are similar to the previous findings that the properties of serotonin, histamine and norepinephrine receptors in the rabbit aorta were different from those in other muscles.

Animals↗
PubMed1988

The selectivity of newly synthesized ergot derivatives to alpha 1- and alpha 2-adrenoceptors, D1- and D2-dopaminergic receptors, muscarinic acetylcholinoceptors and beta-adrenoceptors.

1. We tested affinities of newly synthesized ergot derivatives to alpha 1- and alpha 2-adrenoceptors, D1- and D2-dopamine receptors, muscarinic acetylcholinoceptors and beta-adrenoceptors using radioligand binding techniques. 2. BAM-1110 was alpha 2-selective, though its affinity to alpha 2-adrenoceptors was one tenth less than that of yohimbine. 3. BAM-1303, which was non-selective, had high affinity to alpha-adrenoceptors. The pKi-values for BAM-1303 was 10.11 against both [3H]prazosin (alpha 1-ligand) and [3H]rauwolscine (alpha 2-ligand). 4. New ergot derivatives were selective to D2-dopamine receptors. BAM-1125 and BAM-1303 had high selectivity to D2-receptors. 5. They had less affinity to muscarinic receptors and beta-adrenoceptors.

Animals↗
PubMed1988

Substance P-containing nerves mediate nicotine-induced contractions of rabbit bronchial smooth muscle.

1. A possible role of substance P-containing nerves in the contractile response to nicotine was investigated in isolated rabbit bronchial smooth muscle preparation. 2. Nicotine caused a contraction which was attributed to the release of acetylcholine in the rabbit bronchus. The response was reduced by capsaicin (10(-5) M) and a substance P antagonist, [D-Arg1, D-Pro2, D-Trp7.9, Leu11] substance P (10(-5) M). 3. Substance P (10(-7) M)-induced contraction was reduced by atropine (10(-6) M) and potentiated by physostigmine (10(-6) M). Furthermore, substance P (10-7 M) enhanced the release of tritium or acetylcholine from the [3H]choline labelled bronchi. 4. Results suggest that substance P-like tachykinin accelerates the nicotine-evoked prejunctional endogenous neural release of acetylcholine on the nervous cells in the rabbit bronchial preparation.

Acetylcholine↗
PubMed1988

Pharmacological action of nicotine in the isolated urinary bladder from rabbit: special reference to the chronic nicotine treatment.

1. A mode of action of nicotine and a change of the responsiveness to nicotine following chronic nicotine treatment in the urinary bladder of rabbit were investigated. 2. Nicotine induced only a contraction in the urinary bladder of rabbit, and the response to nicotine was reduced by hexamethonium, atropine and capsaicin. These findings suggest that the contractile response to nicotine was mediated through an action on the nicotinic receptors and partially due to the release of acetylcholine and tachykinins. 3. Tetrodotoxin did not inhibit the contractile response to nicotine in the rabbit detrusor muscle, suggesting that the nicotine-induced response may be produced mainly through a sodium action potential-independent process. 4. Nicotine-induced contraction was reduced following the chronic nicotine treatment without a change of its pharmacological properties. These findings suggest that chronic nicotine treatment might cause a decrease of the amounts of nicotinic receptors and also receptors for mediators released by nicotine.

Animals↗
PubMed1988

Ca-entry blockers, verapamil and diltiazem, on alpha 1-adrenoceptors in thoracic aorta, renal artery and portal vein from rabbit.

1. Verapamil caused a parallel shift of the concentration-response curve for norepinephrine in rabbit thoracic aorta and the reduction in norepinephrine-induced maximum response with shifts of the concentration-response curve for norepinephrine in renal artery and portal vein. 2. Diltiazem was without any effects on the response of thoracic aorta to norepinephrine, while the responses of renal artery and portal vein to norepinephrine were inhibited noncompetitively by diltiazem. 3. Verapamil but not diltiazem diminished markedly dibenamine-induced inhibition of maximum response to norepinephrine in all the preparations used. 4. Specific bindings of [3H]prazosin to both the membrane fractions derived from thoracic aorta and renal artery were displaced concentration-dependently by verapamil and diltiazem, but the effective concentrations of diltiazem were more than those for Ca-entry blocking activity. 5. These results suggest that verapamil might antagonize norepinephrine at alpha 1-adrenoceptors and the effective concentration for Ca-entry blocking activity of diltiazem were less than those for the interaction of diltiazem with alpha 1-adrenoceptors.

Animals↗
PubMed1988

Characterization of nicotine-induced contraction in the canine bronchus.

1. The modes of action of nicotine on the dog bronchial smooth muscle preparation was investigated, in order to compare with those on the bronchial preparations from the guinea-pig, rabbit and monkey. 2. Nicotine induced a contraction in the dog bronchial preparation, and this response was abolished by hexamethonium and atropine and potentiated by physostigmine. 3. These findings suggest that the contractile response to nicotine was mediated through an action on the nicotinic receptors and due to the release of acetylcholine. 4. Tetrodotoxin did not inhibit the contractile response to nicotine in the dog bronchial preparation, suggesting that the nicotine-induced response may be produced mainly through a sodium action potential-independent process. 5. The present observations in the dog bronchial preparations coincided with those in the rabbit and monkey bronchi but not with the findings in the guinea-pig bronchus.

Animals↗
PubMed1988

Mechanism of action of nicotine in isolated iris sphincter preparations of rabbit.

1. Nicotine produced a transient contraction of rabbit isolated iris sphincter muscle, a parasympathetic ganglion-free tissue. The response to nicotine was antagonized by hexamethonium, but was insensitive to tetrodotoxin (TTX). While single treatments with atropine, capsaicin or [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP) partially blocked the response, combined treatment abolished it. 2. Chronic treatment of animals with nicotine added to the drinking water (about 12 mg kg-1 per day) had no effect on the responsiveness to nicotine or the pharmacological properties of nicotine-induced contraction. 3. These results suggest that acetylcholine and tachykinin(s) released via sodium channel-independent mechanisms from nerve terminals of parasympathetic and primary sensory nerves, respectively, are involved in the nicotine-induced contractile response.

Animals↗
PubMed1988

Mechanism of action of nicotine in isolated urinary bladder of guinea-pig.

1. Nicotine produced a transient contraction of isolated strips of guinea-pig urinary bladder. The response to nicotine was antagonized by the nicotinic receptor antagonist, hexamethonium but was insensitive to tetrodotoxin. 2. The nicotine-induced contraction was potentiated by the cholinesterase inhibitor, physostigmine, and was reduced to 50% and 70% by the muscarinic cholinoceptor antagonist, atropine and the sympathetic neurone blocking drug, guanethidine, respectively. Chemical denervation with 6-hydroxydopamine abolished the inhibitory effect of guanethidine. Simultaneous treatment with atropine and guanethidine did not abolish the response to nicotine, but the degree of inhibition was comparable to that obtained with atropine alone. 3. The nicotine-induced contraction was insensitive to bunazosin and yohimbine (alpha 1- and alpha 2-adrenoceptor antagonists, respectively), and exogenously applied noradrenaline did not cause a contraction even in the presence of blockade of noradrenaline uptake mechanisms with desipramine and normetanephrine and of beta-adrenoceptors with propranolol, suggesting a non-adrenergic nature of the sympathomimetic effect of nicotine in this tissue. 4. The nicotine-induced contraction in the presence of atropine was abolished after desensitization of P2-purinoceptors with alpha, beta-methylene adenosine 5'-triphosphate, a slowly degradable ATP analogue selective for P2-purinoceptors. By this desensitization, the response to ATP, but not to histamine, was also abolished. 5. A cyclo-oxygenase inhibitor flurbiprofen partially inhibited the nicotine-induced contraction. The degree of the inhibition was more pronounced in the presence of atropine than in its absence. Flurbiprofen antagonized the response to exogenously applied ATP in an unsurmountable manner, but not that to carbachol. 6. The present results suggest that nicotine might induce a contraction through an interaction with nicotinic receptors located on the terminals of, possibly, (i) parasympathetic cholinergic, (ii) sympathetic non-adrenergic and (iii) non-sympathetic purinergic nerves in guinea-pig detrusor preparations, and that a portion of the contraction due to the purine nucleotide released is possibly potentiated by intramural prostaglandin(s). Parasympathetic cholinergic output might be modulated by an unknown excitatory substance released by nicotine from sympathetic nerve. 7. Nicotine reveals a latent excitatory effect of the sympathetic hypogastric nerve which innervates guinea-pig detrusor.

Animals↗
PubMed1988

Binding of [3H]befunolol to beta-adrenoceptors in cardiac muscles of fetal and neonatal rat.

Characterization of beta-adrenoceptors was studied in heart muscles of rat fetus and neonate. The results of binding assay with [3H]befunolol, a beta-adrenergic partial agonist, to membrane fractions from rat heart muscles indicate that beta-adrenoceptors contain two different affinity sites. In the presence of 5'-guanylylimidodiphosphate, the low affinity site was reduced, while the high affinity site was not affected. The dissociation constants for both sites did not change during pre- and post-natal development. But the maximum binding sites for both sites decreased slightly but significantly (p less than 0.05) during development. A 10-fold decrease in norepinephrine sensitivity and isoprenaline sensitivity during pre- and post-natal development was not explained by the slight decrease in the maximum binding sites.

Adrenergic beta-Antagonists↗
PubMed1988

Two apparently distinct muscarinic cholinoceptor mechanisms in guinea-pig taenia caecum.

Thirty-min treatment of guinea-pig taenia caecum with 300 nM propyl-benzilylcholine mustard (PrBCM) shifted the concentration-response curve for carbachol to the right with a reduction of the maximum contraction, but 90-min treatment did not result in further inhibition. Under these conditions, pilocarpine hardly contracted the preparations, and it competitively antagonized carbachol. Muscarinic agonists might interact with two types of receptor mechanisms and carbachol elicited a stimulus from both types, whereas pilocarpine did so predominantly from the PrBCM-sensitive one.

Animals↗
PubMed1988

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

1. The effects of cooling from 37 degrees C to 25 degrees C on alpha-1-adrenoceptor mechanisms in isolated rat aortic strips were studied. 2. The dissociation constant and the maximum binding for [3H]-prazosin, and the pA2-values (negative logarithm of dissociation constant) of clonidine and prazosin against noradrenaline were not influenced by cooling. 3. These results indicate that cooling did not influence the affinity of a competitive antagonist and receptor concentration. 4. Cooling increased the dissociation constant of noradrenaline but decreased its efficacy. 5. A receptor occupancy-response curve for noradrenaline was a rectangular hyperbola at 37 degrees C but linear at 25 degrees C, suggesting that a relationship between the contractile response and receptor occupancy was changed by cooling.

Animals↗
PubMed1987

Pharmacological evidence for the possible coexistence of multiple receptor sites for mammalian tachykinins in rabbit iris sphincter smooth muscle.

Contractile responses to neurokinin alpha and neurokinin beta were characterized and compared with those to substance P (a SP-P agonist) and eledoisin (a SP-E agonist) in isolated rabbit iris sphincter. Neurokinin alpha and neurokinin beta as well as substance P and eledoisin produced atropine- and tetrodotoxin-resistant contractions of the iris sphincter in nanomolar concentrations, and the rank order of sensitivity was eledoisin greater than substance P = neurokinin alpha = neurokinin beta. After prolonged cold-storage of the preparations, responses to capsaicin, a releaser of tachykinins from sensory nerve endings, were nearly absent, but responses of considerable magnitude to carbachol and the tachykinins persisted. On wash-out of the tachykinins, responses faded at characteristic rates (neurokinin alpha greater than eledoisin greater than neurokinin beta much greater than substance P). From the Schild analyses, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P, a potent substance P antagonist, competitively antagonized the response to substance P, had no significant effect on the response to neurokinin beta, and antagonized the response to neurokinin alpha and eledoisin in a more complex manner. Taken together, these results suggest that there coexist multiple receptor sites for mammalian tachykinins in rabbit iris sphincter smooth muscle.

Animals↗
PubMed1987

(+/-)-1-[[2-(3,4-Dimethoxphenyl)ethyl]amino]-3-(3-methylphenoxy)-2- propanol hydrochloride (bevantolol, NC-1400) as a beta 1-selective adrenoceptor blocker with alpha 1-adrenoceptor blocking activity.

Blocking activities of alpha- and beta-adrenoceptors by (+/-)-1-[[2-(3,4-dimethoxyphenyl)-ethyl]amino]-3-(3-methylphenoxy)-2 -propanol hydrochloride (NC-1400) were tested on the isolated muscles, comparing with those of labetalol and atenolol. In blocking the beta 1-adrenoceptor, NC-1400 was slightly more potent than labetalol and atenolol. NC-1400 was about 1/10th as potent as labetalol and about ten times as potent as atenolol in blocking the beta 2-receptor. NC-1400 was beta 1-adrenoceptor selective. NC-1400 was about 1/30th as potent as labetalol in blocking the alpha 1-receptor. NC-1400 did not interact with the alpha 2-adrenoceptor in concentrations up to 10(-5) M. The present results indicate that NC-1400 is the selective beta 1-adrenoceptor blocker with some blocking activity of alpha 1-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1987

cis(-)-2,3-Dihydro-3-(4-methylpiperazinylmethyl)-2-phenyl-1,5- benzothiazepin-4(5H)-one monohydrochloride and its butylbromide as M1-receptor antagonists.

Selectivity of cis(-)-2,3-dihydro-3-(4-methylpiperazinylmethyl)-2-phenyl-1,5-b enzothiazepin-4 (5H)-one monohydrochloride (BTM-1086) and its butylbromide (BTM-1073) to subtypes of muscarinic receptor, M1-and M2-receptors were tested, using pirenzepine, a M1-selective antagonist and atropine, a nonselective antagonist as reference drugs. Like pirenzepine, BTM-1086 and BTM-1073 were M1-selective antagonists. BTM-1086 was most selective among the test drugs. BTM-1073, a butylbromide of BTM-1086 was more potent than BTM-1086 in antimuscarinic activity tested on the isolated ileal longitudinal muscle, suggesting that quarternarization increased selectivity to M2-receptor but not to M1-receptor.

Acetylcholine↗
PubMed1987

Effects of nitro compounds, isosorbide dinitrate, 5-isosorbide mononitrate and glyceryl trinitrate on Ca-uptake into Ca-stores and Ca-release from Ca-stores in rabbit isolated femoral veins and femoral arteries.

In organ bath studies, effects of isosorbide dinitrate (ISDN), 5-isosorbide mononitrate (ISMN), a major metabolite of ISDN, and glyceryl trinitrate (GTN) on Ca-uptake into Ca-stores and Ca-release from Ca-stores were tested in the rabbit isolated femoral veins and femoral arteries. ISDN (10(-4) M) and GTN (10(-4) M) inhibited Ca-uptake in the femoral veins but not in the femoral arteries. The selectivity to the femoral veins was not observed in ISMN (10(-3) M) and GTN (3 X 10(-6) M). All the nitro compounds inhibited Ca-release from Ca-stores more effectively in the femoral veins than in the femoral arteries. The present results may explain the selectivity of the nitro compounds to the femoral veins.

Animals↗
PubMed1987

Postsynaptic alpha 1-adrenoceptor mechanisms in rat vas deferens and ageing.

Postsynaptic alpha 1-adrenoceptor mechanisms in vasa deferentia isolated from 3, 6, 18 and 40 week-old rats were studied by analysis of the concentration-response curve of noradrenaline and the Scatchard plot of specific binding of [3H]prazosin to microsomal fractions. The maximum tension developed by noradrenaline also increased with age from 3 to 18 weeks. The efficacy of noradrenaline and capacity of the maximum binding sites of [3H]prazosin increased with increasing age, while the dissociation constants of noradrenaline (KA) and prazosin (Kd) were not changed with age. The increase of the maximum tension was proportional to the increase in efficacy. The increase of efficacy for noradrenaline in the vasa deferentia from rats of different ages is due to the increase in the total concentration of postsynaptic alpha 1-adrenoceptors.

Aging↗