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Y Kamikawa

Publications and source records attributed to Y Kamikawa.

At least 55 records · Page 3Linked to original sources
PubMed1991

Inhibitory effects of non-narcotic antitussive drugs on cholinergically and non-cholinergically mediated neurogenic contractions of guinea-pig isolated bronchial muscle.

We have examined the actions of non-narcotic antitussive drugs on the response evoked by electrical field stimulation or by acetylcholine (ACh) and neurokinin A (NKA) on guinea-pig bronchial strip chain. Electrical field stimulation (1-32 Hz, 0.5 ms, 30 V for 5 s) evoked a biphasic contraction in a frequency-dependent manner, consisting of a cholinergically mediated fast contraction followed by a non-cholinergically mediated slow contraction. Dextromethorphan (1-300 microM) and tipepidine (0.1-100 microM) caused a concentration-dependent inhibition in the height of the biphasic contraction, but noscapine (1-300 microM) was less effective. Submaximal contractions of bronchial muscle evoked by exogenous ACh (1-30 microM) were inhibited by tipepidine (10-100 microM), but not by dextromethorphan (10-100 microM) or noscapine (10-100 microM), while those evoked by exogenous NKA (10-300 nM) were augmented by these drugs. The results indicate that in guinea-pig isolated bronchial muscle, dextromethorphan inhibited both neurally-mediated responses but not those to the exogenously applied agent. Tipepidine caused an inhibition similar to the non-cholinergically mediated response of dextromethorphan, it also caused a more profound inhibition of the cholinergically mediated response and selectively antagonized ACh. Noscapine had no effect.

Animals↗
PubMed1990

Modulating effects of antiasthmatic and antitussive drugs on autonomic neurotransmission in guinea-pig bronchial muscle in vitro.

Electrical field stimulation evoked a biphasic contraction of the guinea-pig isolated bronchi, consisting of a cholinergically mediated fast contraction followed by a non-cholinergically mediated slow contraction. Catecholamines, beta 2-stimulants, methylxanthines, antiallergic drugs, narcotic and non-narcotic antitussive drugs inhibited the neurogenic contractions not only by postjunctional depression of the response but also by prejunctional reduction of the transmitter release.

Animals↗
PubMed1990

Inhibitory effects of catecholamines on cholinergically and non-cholinergically mediated contractions of guinea-pig isolated bronchial muscle.

The actions of catecholamines on the responses evoked by electrical field stimulation or by acetylcholine and substance P in guinea-pig bronchial strip chain have been examined. Electrical field stimulation evoked a biphasic contraction, consisting of a cholinergically-mediated fast contraction followed by a non-cholinergically-mediated slow contraction. All catecholamines tested caused a concentration-dependent reduction in the height of the biphasic contraction, where non-cholinergic contractions were more potently inhibited. The inhibitory effect of isoprenaline was largely prevented by propranolol (2 microM) alone, whereas those of noradrenaline and adrenaline were prevented by treatment with both propranolol (2 microM) and yohimbine (2 microM). The inhibitory effect of dopamine was unaffected either by propranolol (2 microM), yohimbine (2 microM) or haloperidol (10 microM). Submaximal contractions of bronchial muscle evoked by exogenous acetylcholine (2 microM) or substance P (0.2 microM) were also inhibited by catecholamines, except dopamine, but the effects were antagonized by propranolol (2 microM) alone. The results suggest that in guinea-pig isolated bronchial muscle, catecholamines can inhibit both cholinergic and non-cholinergic excitatory neurotransmissions not only by postjunctional beta-adrenoceptors but also by prejunctional alpha 2-adrenoceptors.

Animals↗
PubMed1990

Morphine and opioid peptides selectively inhibit the non-cholinergically mediated neurogenic contraction of guinea-pig isolated bronchial muscle.

The experiments examine the actions of morphine and opioid peptides on the responses evoked by electrical field stimulation or by acetylcholine (ACh) and substance P (SP) in guinea-pig bronchial strip chain. Electrical field stimulation evoked a biphasic contraction, consisting of a cholinergically mediated fast contraction followed by a non-cholinergically mediated slow contraction. Morphine and opioid peptides caused a concentration-dependent inhibition in the height of the non-cholinergic contraction. The order of inhibitory activity was BW443C greater than dynorphin greater than morphine greater than beta-endorphin greater than leucine-enkephalin greater than methionine-enkephalin. Cholinergically mediated contractions were less potently inhibited by these opioids. Submaximal contractions of bronchial muscle evoked by exogenous ACh (2 microM) or SP (0.2 microM) were not inhibited by morphine (100 microM) or opioid peptides (3-10 microM), rather, they were augmented. The results indicate that in guinea-pig isolated bronchial muscle, morphine and opioid peptides can selectively inhibit excitatory non-cholinergic neurotransmission via prejunctional opioid receptors.

Acetylcholine↗
PubMed1989

Adenosine selectively inhibits noncholinergic transmission in guinea pig bronchi.

The neuromodulatory action of adenosine and ATP was investigated in isolated guinea pig bronchial strip chain preparations contracted with electrical field stimulation. The tissues were placed in organ baths containing physiological salt solution and stimulated at 8-Hz frequency, 0.5-ms pulse duration, and 30 V (approximately 100 mA) for 5 s. Electrical field stimulation evoked a biphasic contraction of bronchial muscle, consisting of an initial contraction followed by a sustained contraction, which was mediated by intramural cholinergic and noncholinergic nerve stimulations, respectively. Adenosine, at concentrations greater than M, caused a concentration-dependent inhibition in the height of the noncholinergically mediated contraction, accompanied by a very weak inhibition on the cholinergically mediated response. ATP (10(-5) to 3 x 10(-3) M) also produced a similar inhibitory effect on the noncholinergically mediated contraction, but the inhibitory potency was less than that of adenosine. The inhibitory response to adenosine was enhanced by the pretreatment with dipyridamole (2 x 10(-6) M) but antagonized with aminophylline (10(-5) M). Contractions of bronchial muscle evoked by exogenous acetylcholine (2 x 10(-6) M) or substance P (2 x 10(-7) M) were significantly inhibited by the adenosine (3 x 10(-4) M) pretreatment. These data suggest that in isolated guinea pig bronchi adenosine selectively inhibits noncholinergic neurotransmission through prejunctional P1-purinoceptors.

Acetylcholine↗
PubMed1989

Inhibitory effect of anti-allergic drugs on cholinergic and non-cholinergic neurotransmissions of guinea pig bronchial muscle in vitro.

To determine whether anti-allergic drugs can inhibit autonomic neurotransmission of airway smooth muscle, we studied the effect of sodium cromoglycate (SCG, Intal) and related anti-allergic drugs on electrically induced neurogenic contractions of isolated guinea pig bronchial muscle. Electrical field stimulation (8 Hz, 0.5 msec, 30 V) evoked a biphasic contraction of bronchial muscle, consisting of an initial phasic component followed by a sustained one which was mediated by cholinergic and non-cholinergic nerve stimulations, respectively. Sodium cromoglycate, tranilast, ketotifen, and azelastine at concentrations higher than 10(-6) M caused a concentration-dependent inhibition in the height of the non-cholinergically mediated contractions. The cholinergically mediated contractions were also inhibited by tranilast, ketotifen, and azelastine but not by SCG. Submaximal contractions of bronchial muscle evoked by exogenous substance P (2 X 10(-7) M) were less potently inhibited by these drugs than those by exogenous acetylcholine (2 X 10(-6) M). These results indicate that in isolated guinea pig bronchial muscle, anti-allergic drugs may inhibit non-cholinergic neurotransmission mainly by prejunctional reduction of the transmitter release and partly by postjunctional depression of the response.

Acetylcholine↗
PubMed1989

[Synergistic interaction between anti-allergic drugs and beta 2-stimulants on neurogenic contractions of guinea-pig isolated bronchial muscle].

The inhibitory effect of beta 2-stimulants on neurogenic contractions of guinea-pig isolated bronchial strip-chain was examined after or without pretreatment with sodium cromoglycate (SCG, 10(-5) M). Electrical field stimulation (8 Hz, 0.5 msec, 30 V, 40 pulses) evoked a biphasic contraction of the bronchial muscle, consisting of an initial phasic component followed by a sustained one which was mediated by cholinergic and peptidergic nerve stimulations, respectively. Both terbutaline and clenbuterol caused a concentration-dependent inhibition in the height of the electrically-induced biphasic contraction. Concentration-response curves for the inhibitory actions of these beta 2-stimulants were shifted to the left by pretreatment with SCG or tranilast, and the peptidergic contractions were more potently inhibited than the cholinergic contractions. Terbutaline and clenbuterol also inhibited submaximal contractions to exogenously applied acetylcholine (2 x 10(-6) M) or substance P (2 x 10(-7) M), but the actions were not modified by pretreatment with SCG or tranilast. These results indicate that combined treatments with anti-allergic drugs and beta 2-stimulants can synergistically inhibit neurogenic contractions of guinea-pig bronchial muscles.

Acetylcholine↗
PubMed1989

[Inhibitory effect of bronchodilators on cholinergic and peptidergic contractions of guinea-pig isolated bronchial muscle].

The effect of bronchodilators on neurogenic contractions was studied using isolated bronchial strip-chain preparations from guinea-pigs. Electrical field stimulation (8 Hz, 0.5 msec, 30 V, 40 pulses) evoked a biphasic contraction of the bronchial muscle, consisting of an initial phasic component followed by a sustained one which was mediated by cholinergic and peptidergic nerve stimulations, respectively. All the beta-stimulants and xanthines tested caused a concentration-dependent inhibition in the height of the electrically-induced biphasic contraction, with the following order of potency: procaterol greater than fenoterol greater than salbutamol greater than isoproterenol greater than adrenaline greater than enprofylline greater than aminophylline greater than ephedrine. Ipratropium bromide selectively inhibited the electrically-induced cholinergic contraction. Submaximal contractions of the bronchial muscle evoked by exogenous substance P (2 X 10(-7)M) were less potently inhibited by these drugs than those evoked by exogenous acetylcholine (2 X 10(-6)M). These results indicate that in isolated guinea-pig bronchial muscle, bronchodilators may inhibit cholinergic and peptidergic neurotransmissions mainly by postsynaptic depression of the responsiveness and partly by presynaptic reduction of the transmitter release.

Animals↗
PubMed1987

Different spasmolytic effects of smooth muscle relaxants on the guinea-pig esophageal muscularis mucosae contracted by carbachol or high potassium in vitro.

The responsiveness of the guinea-pig esophageal muscularis mucosae to smooth muscle relaxants was examined in vitro during the contractile state induced by carbachol (3 microM) or high potassium (60 mM). In the presence of phentolamine (3 microM), all catecholamines tested (10 nM-30 microM) relaxed the carbachol-induced tone more effectively than the high potassium-induced tone, and the maximum relaxations reached about 90-95% for carbachol but only about 40% for high potassium. Verapamil produced a concentration-dependent relaxation of the muscularis mucosae precontracted with either spasmogen; the mean EC50 values (-log M) were 6.73 for high potassium and 4.65 for carbachol. Methylene blue (1-300 microM) relaxed the carbachol-contracted muscularis mucosae in a concentration-dependent manner but relaxed the high potassium-contracted one less potently. Forskolin (1-300 microM), papaverine (1-100 microM), aminophylline (10-300 microM), trifluoperazine (1-300 microM), 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (10-300 microM), quinacrine (1-300 microM) and dibutyryl cyclic AMP (100 microM-3 mM) produced relaxation almost equipotently in both contractile states whereas adenosine (10 microM-1 mM), sodium nitroprusside (10-300 microM) and dibutyryl cyclic GMP (100 microM-3 mM) were virtually ineffective. The present results indicate that a variety of smooth muscle relaxants have different spasmolytic effects on the guinea-pig isolated esophageal muscularis mucosae which was precontracted with carbachol or high potassium and that catecholamines and methylene blue may produce relaxation independent of the changes in intracellular cyclic nucleotides, calmodulin or phosphoinositides.

Animals↗
PubMed1986

Inhibitory effects of sympathomimetic drugs on cholinergically mediated contractions of guinea-pig isolated tracheal muscle.

The experiments examine the actions of sympathomimetic drugs on the responses evoked by electrical field stimulation or by acetylcholine in guinea-pig tracheal strip chains. Electrical field stimulation evoked contractions which were cholinergically mediated, in the presence of guanethidine (10 microM) and indomethacin (2 microM). All the sympathomimetic drugs tested caused a concentration-dependent reduction in the height of these contractions. Inhibitory effects of isoprenaline and terbutaline were largely prevented by propranolol (2 microM) alone, whereas those of clonidine, oxymetazoline, lidamidine and WHR1370 were prevented by yohimbine alone (2 microM). Treatments with both propranolol and yohimbine were required to prevent the inhibitory effects of noradrenaline, adrenaline and dopamine. Contractions evoked by exogenous acetylcholine (0.1-3 microM) were also inhibited by all catecholamines and terbutaline, but not by clonidine, oxymetazoline, lidamidine and WHR1370. The inhibitory effects were antagonized by propranolol (2 microM) alone. The results suggest that in guinea-pig isolated tracheal muscle, sympathomimetic drugs can inhibit cholinergic neurotransmission not only by postjunctional beta 2-adrenoceptors but also by prejunctional alpha 2-adrenoceptors.

Acetylcholine↗
PubMed1986

Experimental model of anaphylaxis-induced beta-adrenergic blockade in the airways.

The influence of an anaphylactic challenge on the relaxing effects of isoproterenol, prostaglandin E1 (PGE1), forskolin, and aminophylline was examined using an isolated tracheal muscle preparation from ovalbumin (OA)-sensitized guinea pigs. As compared with histamine (4 X 10(-5) M) challenge, an anaphylactic challenge with OA (5 micrograms/mL) caused a rightward shift of the concentration-response curves for isoproterenol, PGE1, and forskolin but not for aminophylline. Their 50% effective concentrations were increased by about 1.7- to 2.8-fold of the histamine challenged preparations. These results indicate that anaphylactic challenge of the sensitized guinea pig tracheal muscle diminishes relaxing effects of isoproterenol, PGE1, and forskolin but not aminophylline. Possible mechanisms of these subsensitivities may involve both impaired coupling mechanism between receptor and adenylate cyclase and decreased adenylate cyclase activity, rather than their receptor numbers or affinity.

Alprostadil↗
PubMed1986

Alterations of presynaptic and endothelial functions in SHR: effects of adenosine.

The effects of adenosine on stimulation-evoked 3H-efflux from perfused mesenteric arteries pretreated with 3H-norepinephrine and on norepinephrine-induced contractile responses of the thoracic aorta before and after mechanical removal of endothelial cells were examined in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). Adenosine inhibited the stimulation-evoked 3H-efflux; this inhibitory effect was smaller in young and adult SHR than age-matched WKY. Mechanical removal of endothelial cells rendered the SHR aorta much less responsive to adenosine, while in the WKY aorta endothelial removal had no influence on the relaxation response to adenosine. These results support the hypothesis that pre-synaptic factors are contributory whereas endothelial factors are compensatory to hypertension in SHR.

Adenosine↗
PubMed1985

Contractile responses of the guinea-pig esophageal muscularis mucosae in vitro to arachidonic acid and its metabolites.

The responsiveness of the guinea-pig esophageal muscularis mucosae to arachidonic acid (AA) and its cyclooxygenase and lipoxygenase metabolites was examined in vitro. AA (0.1-30 microM) produced a concentration-dependent contraction of the muscularis mucosae (mean EC50 +/- S.E.M. = 5.1 +/- 1.0 microM). The contractions in response to low concentrations of AA (0.1-3 microM) were prevented by pretreatment of the tissue with indomethacin (1-10 microM), while those in response to high concentrations (10-100 micron) were prevented by BW755C (10-100 microM). The contractile response to AA was antagonized by polyphloretin phosphate (PPP, 1-10 micrograms/ml) and by FPL 55712 (1-10 microM). All cyclooxygenase and lipoxygenase metabolites of AA tested also produced a sustained contraction of the muscularis mucosae with the following order of sensitivity; leukotriene (LT) D4 greater than LTC4 greater than prostaglandin (PG) E2 greater than PGF2 alpha greater than PGI2 greater than thromboxane B2. The responses to LTC4 and LTD4 were antagonized by FPL 55712 (0.1-1 microM), while those to PGE2 and PGF2 alpha were antagonized by PPP (3-100 micrograms/ml). The present results indicate that exogenously applied AA contracts the isolated muscularis mucosae of the guinea-pig esophagus by an indirect action via its metabolism to both PGs and LTs. The putative PG and LT receptors located in this tissue are probably similar to those in the ileal longitudinal muscle, but differ from those in the airway smooth muscle.

Animals↗
PubMed1985

Heterogeneity of muscarinic receptors in the guinea pig esophageal muscularis mucosae and ileal longitudinal muscle.

Pharmacologic characteristics of muscarinic receptors in the muscularis mucosae of the guinea pig esophagus were examined in vitro and compared with those of the longitudinal muscle of the guinea pig ileum. All cholinomimetics tested produced a sustained contraction of the muscularis mucosae, in a concentration-dependent manner, which was associated with a small biphasic change in membrane potential, initially a hyperpolarization followed by a depolarization. The contractile response was hardly modified by verapamil, but was depressed by calcium removal from the bathing medium. Both atropine and pirenzepine antagonized the contractile response in a competitive manner, with higher pA2 values than those in the ileum. These results indicate that the muscarinic receptors of the muscularis mucosae of the guinea pig esophagus mainly link with calcium ion channels which are independent of changes in membrane potential and that their subtype populations are probably pharmacologically distinct from those in the ileal longitudinal muscle.

Animals↗
PubMed1985

Pharmacological characterization of the histamine receptor in the isolated muscularis mucosae of the guinea-pig oesophagus.

To characterize the histamine receptors in the muscularis mucosae, the isotonic responsiveness of the isolated muscularis mucosae of the guinea-pig oesophagus to histamine receptor agonists and antagonists was examined in vitro. Histamine (0.1-100 microM) produced a concentration-dependent contraction of the muscularis mucosae (EC50 = 1.6 +/- 0.2 microM). The contractions were rapid in onset, sustained, reversible by washing and the preparation did not show tachyphylaxis. 2-Methylhistamine (2-MH), 2-pyridylethylamine (PEA) and 4-methylhistamine (4-MH) produced similar sustained contractions of the muscularis mucosae. The order of sensitivity was histamine greater than 2-MH greater than PEA greater than 4-MH. Impromidine (10-300 microM) and dimaprit (10-300 microM) caused no response in this tissue. The contractile responses to histamine, 2-MH, and PEA were competitively antagonized by diphenhydramine, and the pA2 values were almost the same (approximately 8.1). Cimetidine (100 microM) could not modify the contractile response to these agonists. The contractile response to histamine was slightly inhibited by tetrodotoxin (0.3 microM), atropine (1 microM), indomethacin (0.1-3 microM) or aspirin (30-300 microM), and the EC50 value was increased about 2-6 times by these drugs. When the preparation was incubated in Tyrode solution containing various calcium concentrations (0, 0.45, 0.9 and 1.8 mM), the concentration-response curve to histamine was shifted to the right and downward; the effect was inversely dependent on the calcium concentration, and in a calcium-free medium the response to histamine was abolished. Verapamil (1-10 microM) partially inhibited the contractile response to histamine. 7 The present results indicate that the contraction of the guinea-pig oesophageal muscularis mucosae to histamine is mediated mainly by a direct action on the smooth muscle and partly by indirect actions via the stimulation of either endogenous prostaglandin biosynthesis or intramural cholinergic nerves. The histamine receptors responsible for contractions of this tissue are probably mainly of the H,- subtype with H2-receptors having a negligible role.

Animals↗
PubMed1984

Contractile responses to substance P and related peptides of the isolated muscularis mucosae of the guinea-pig oesophagus.

The site of action of substance P and related tachykinins with respect to isotonic contractions was examined on the isolated muscularis mucosae attached to the submucous plexus of the guinea-pig oesophagus. Substance P (greater than 30 nM) produced a concentration-dependent contraction of the muscularis mucosae (EC50 1.9 +/- 0.5 microM, n = 10). The contractions were rapid in onset (2 min or less), sustained, reversible by washing and the preparation did not show tachyphylaxis. Eledoisin and physalaemin produced similar sustained contraction of the muscularis mucosae. The order of sensitivity was eledoisin greater than substance P greater than physalaemin. Contractions induced by 1 microM of each tachykinin were not significantly modified by incubation of the tissue with substance P or eledoisin (10 microM for 30 min). The contractile responses to tachykinins were unaffected by tetrodotoxin (0.3 microM), atropine (0.3 microM), phentolamine (1 microM), chlorpheniramine (1 microM), methysergide (1 microM), baclofen (100 microM) and verapamil (10 microM), but were abolished by the incubation of the tissue with calcium-free, EGTA (0.1 mM)-containing Tyrode solution. A substance P antagonist, [D-Pro2, D-Trp7,9]-substance P (greater than 0.1 microM), produced a transient contraction of the muscularis mucosae and the smooth muscle regained its original tone within 6 to 10 min. Contractions to the tachykinins were now inhibited by the antagonist (0.1-10 microM) in a concentration-dependent manner, the order of sensitivity being physalaemin greater than substance P = eledoisin. The cholinergically mediated electrically (0.1 Hz, 0.5 ms, supramaximal voltage)-induced twitch contractions of the muscularis mucosae were not significantly modified by substance P (0.01-0.3 microM). 7 The present results indicate that substance P and related tachykinins contract the isolated muscularis mucosae of the guinea-pig oesophagus by a direct action on the smooth muscle, probably by stimulating SP-E receptors.

Animals↗
PubMed1983

Indirect action of 5-hydroxytryptamine on the isolated muscularis mucosae of the guinea-pig oesophagus.

1 The site of action of 5-hydroxytryptamine (5-HT) was examined on the isolated muscularis mucosae attached to the submucous plexus of the guinea-pig oesophagus. Isotonic responses of the longitudinal muscularis mucosae were recorded.2 5-HT produced a transient contraction of the muscularis mucosae at concentrations higher than 3 muM. The contraction was rapid in onset, reaching a peak in about 15 s or less, and was restored to the basal level after 20 to 30 s without washing out 5-HT. When the 5-HT-induced contraction faded to the basal tone, successive applications of 5-HT no longer produced any contracture.3 Nicotine (Nic), at concentrations higher than 10 muM, also produced a transient contraction which had a very similar pattern to that induced by 5-HT. Again, the successive application of Nic no longer produced any contracture following prior treatment with Nic itself. However, the 5-HT-induced contraction was not modified by the presence of Nic.4 Exogenously applied acetylcholine (ACh) produced a concentration-dependent contraction of the muscularis mucoase, the 50% effective concentration (EC(50)) was 69 +/- 5.6 nM. The contraction was sustained during incubation with ACh, and was not modified by prior treatment with 5-HT or Nic.5 The 5-HT (100 muM)-induced contraction was completely abolished by tetrodotoxin (0.2 muM) and atropine (0.2 muM). This means that the action is mediated by stimulating cholinergic nerves in the submucous plexus attached to muscularis mucosae. Moreover, the stimulating action of 5-HT does not involve nicotinic receptors, since the action was not blocked by hexamethonium (100 muM).6 Among several 5-MT antagonists examined, methysergide (1 muM), ketanserin (1 muM) and morphine (100 muM) failed to modify the 5-HT (100 muM)-induced contraction significantly. Cinanserin (0.1-3 muM), cyproheptadine (3-100 nM) and phenoxybenzamine (0.1-3 muM) inhibited the 5-HT-induced contraction, in a concentration-dependent manner, and each highest concentration abolished the response. However, none of these antagonists was specific for 5-HT, but the Nic (100 muM) or ACh (0.1 muM)-induced contractions were also inhibited by them.7 The present results indicate that 5-HT contracts the muscularis mucosae of the guinea-pig oesophagus indirectly by stimulating cholinergic nerves in the submucous plexus, and has no direct action on the muscularis mucosae. In addition, the type of 5-HT receptors responsible for the stimulant action may be different from those in other parts of the gastrointestinal tract, blood vessels or brain, because of the different effects of 5-HT antagonists.

Acetylcholine↗