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Biomedical subjects

Y Kamikawa

Publications and source records attributed to Y Kamikawa.

71 records · Page 4Linked to original sources

Pharmacological characterization of the opioid receptor in the submucous plexus of the guinea-pig oesophagus.

1 The cholinergically mediated electrically-induced contractions of the submucous plexus-longitudinal muscularis mucosae preparation of the guinea-pig oesophagus were used to study the actions of opioid peptides and morphine. 2 The twitch contractions of the tissue (0.1 Hz, 0.5 ms, supramaximal voltage) were inhibited by all the opioid peptides and morphine in a concentration-dependent manner. The order of potency was dynorphin-(1-13) greater than alpha-neo-endorphin greater than beta-endorphin greater than [D-Ala2]-methionine-enkephalin much greater than alpha-endorphin, methionine-enkephalin, leucine-enkephalin and morphine. 3 The inhibitory actions of dynorphin-(1-13) (20 nM), alpha-neo-endorphin (100 nM) and beta-endorphin (3 microM) were completely reversed either by naloxone (1 microM) or by morphine (100 microM). The Ke values of naloxone against dynorphin-(1-13) and alpha-neo-endorphin were 30 and 25 nM, respectively. 4 Increasing the concentration of calcium from 1.8 to 3.6 mM in Tyrode solution decreased the sensitivity of the tissue to dynorphin-(1-13) 7.4 times and to alpha-neo-endorphin 462 times. 5 The inhibitory actions of dynorphin-(1-13) (100 nM) and alpha-neo-endorphin (300 nM) were inversely related to stimulus frequency, being most active at low frequencies (0.1-1 Hz), and least active at high (30 Hz). 6 Exogenously applied acetylcholine produced concentration-dependent contractions of the isolated muscularis mucosae, with an EC50 of 72.6 +/- 4.5 nM. The contractile response of the oesophagus to acetylcholine was not affected by the pretreatment of the tissue with dynorphin-(1-13) (100 nM), alpha-neo-endorphin (300 nM) or beta-endorphin (3 microM). 7 It is concluded that the submucous plexus-longitudinal muscularis mucosae of the guinea-pig oesophagus is inhibited by opioid peptides acting at prejunctional opioid receptors, probably of the kappa-subtype.

Acetylcholine↗

Inhibitory actions of catecholamines on electrically induced contractions of the submucous plexus-longitudinal muscularis mucosae preparation of the guinea-pig oesophagus.

1 The submucous plexus-longitudinal muscularis mucosae preparation of the guinea-pig oesophagus was used to study the actions of catecholamines on the twitch responses to electrical stimulation.2 When the preparation was stimulated coaxially (0.1 Hz, 0.5 ms, supramaximal voltage), stable twitch-like contractions were obtained. These were abolished by tetrodotoxin (0.1 muM) and atropine (0.1 muM), potentiated by physostigmine (0.1 muM), and were mediated presumably by stimulation of intramural cholinergic nerves.3 The twitch contractions of the muscularis mucosae were inhibited by catecholamines, in a concentration-dependent manner. The order of potency was isoprenaline > adrenaline > noradrenaline > dopamine.4 The inhibitory actions of noradrenaline (1 muM) and adrenaline (1 muM) were partly reversed by phentolamine (1 muM) or by propranolol (1 muM), and completely abolished by both antagonists together. The inhibitory effect of dopamine (300 muM) was largely reversed by phentolamine (1 muM), but not by propranolol (1 muM), while the inhibitory action of isoprenaline was competitively antagonized only by propranolol (pA(2) of 7.6).5 The contraction of the muscularis mucosae to exogenously applied acetylcholine (ACh, 20 nM) which was comparable in magnitude with that to electrical stimulation was also inhibited by isoprenaline (0.1 muM), adrenaline (1 muM) and noradrenaline (1 muM), but not by dopamine (300 muM). In the presence of propranolol (1 muM), noradrenaline, adrenaline and dopamine potentiated the ACh-induced contraction, while the effect of isoprenaline was mainly antagonized. The potentiating effects were antagonized by further treatment with phentolamine (1 muM).6 Adrenaline, noradrenaline and dopamine but not isoprenaline, produced a weak contraction of the longitudinal muscularis mucosae in the presence of propranolol (3 muM). The contractile responses were completely inhibited by phentolamine (3 muM). Tone in the muscularis mucosae induced by carbachol (3 muM) in the presence of phentolamine (10 muM) was inhibited by catecholamines, in a concentration-dependent manner, an effect that was competitively antagonized by propranolol.7 In the submucous plexus-longitudinal muscularis mucosae preparation of the guinea-pig oesophagus there are three types of adrenoceptor, inhibitory prejunctional alpha-adrenoceptors, excitatory postjunctional alpha-adrenoceptors and inhibitory postjunctional beta-adrenoceptors, and cholinergic neurotransmission is inhibited by catecholamines acting at both prejunctional alpha- and postjunctional beta-adrenoceptors.

Animals↗

Diminished purinergic modulation of the vascular adrenergic neurotransmission in spontaneously hypertensive rats.

The inhibitory effects of adenosine and ATP on the pressor response of the perfused mesenteric vascular bed to perivascular adrenergic nerve stimulation were compared between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKR). Both adenosine and ATP inhibited the neurogenic vasoconstriction in a dose-dependent manner in WKR, in which the inhibitory effect of adenosine was approximately eight times greater than that of ATP on the basis of 50% inhibitory doses (ID50). In the same preparation isolated from SHR, the inhibitory effects of both adenosine and ATP were significatly smaller than that in WKR. The ID50 values in the SHR for both agonists were approximately six times those found in WKR. These compounds also inhibited the pressor response to norepinephrine (0.3 microgram/ml) infusion, but the degrees of inhibition were markedly less than those with the neurogenic pressor response, and were not significantly different between WKR and SHR. These results suggest that presynaptic inhibition of vascular adrenergic neurotransmission by purine compounds is reduced in SHR.

Adenosine↗

Cholinergic and adrenergic innervations of the muscularis mucosae in guinea-pig esophagus.

Transmural stimulation of the isolated muscularis mucosae from guinea-pig esophagus induced contraction, which was completely inhibited by the pretreatment with atropine (o.1 microM) or tetrodotoxin (0.1 microM). In the presence of atropine, muscularis mucosae which contracted with histamine 2 microM slightly relaxed by transmural stimulation in 8 out of 20 preparations. The relaxation was inhibited by an addition of guanethidine (10 microM) or propranolol (2 microM). The vagal stimulation or an addition of nicotine also induced contractions of muscularis mucosae which were blocked by hexamethonium (20-50 microM), tetrodotoxin (0.1 microM) or atropine (0.1 microM). Using the formaldehydeinduced fluorescence technique, a few catecholamine-containing nerve fibres were observed in muscularis mucosae or in the wall of small blood vessels of guinea-pig esophagus. From these results, it is suggested that muscularis mucosae in guinea-pig esophagus is innervated mostly with excitatory cholinergic nerves, and sparsely with inhibitory adrenergic nerves, but not with non-adrenergic and non-cholinergic nerves.

Animals↗

Antagonistic effect of compound 48/80 on the inhibitory actions of morphine and methionine-enkephalin on electrically-induced contractions of the guinea-pig ileum.

1 The effect of compound 48/80 was studied on the twitch-like contractions of the longitudinal muscle of guinea-pig ileum induced by electrical stimulation of intramural cholinergic nerves. 2 Compound 48/80 alone, at concentrations up to 30 microgram/ml, had no effect on the twitch contractions. The contraction to exogenously applied acetylcholine was slightly depressed by the compound. 3 At 100 microgram/ml, compound 48/80 caused a weak but long-lasting increase in tone and irregular contractile activity in the ileum, part of which was reduced but not completely abolished by pretreatment with chlorpheniramine (1 muM) or by repeated applications of compound 48/80. 4 The inhibitory effects of morphine and methionine-enkephalin on the twitches were antagonized by the presence of compound 48/80 (3 to 30 microgram/ml), possibly in a competitive manner. The antagonism was not affected by pretreatment with the antihistaminics, chlorpheniramine and/or metiamide. 5 The inhibitory effects of noradrenaline and adrenaline on the twitches were slightly but significantly increased by the presence of compound 48/80 (10 or 30 microgram/ml), whereas that of ATP was not modified. 6 Thesese results indicate that compound 48/80 acts as a selective and competitive antagonist at opiate receptors located in the intramural cholinergic nerves of guinea-pig ileum.

Adenine Nucleotides↗

Some possibilities for prostaglandin mediation in the contractile response to ATP of the guinea-pig digestive tract.

Several contractile responses of longitudinal muscles of the guinea-pig digestive tract to exogenously applied ATP (10-300 micrometer), including "rebound" contractions, were inhibited by indomethacin (3-20 micrometer) or polyphloretin phosphate (10-100 microgram/ml). Relaxations to ATP in stomach and large intestinal muscles were increased by these drugs. Prostaglandin release might therefore contribute to the contractile responses of the guinea-pig digestive tract to ATP.

Adenosine Triphosphate↗

Mediation of prostaglandin E2 in the biphasic response to ATP of the isolated tracheal muscle of guinea-pigs.

ATP, at a dose higher than 0-1 mug m1(-1), showed a biphasic action consisting of an initial increase followed by a gradual decrease of muscle tension in the isolated tracheal strip-chains of guinea-pigs. The pattern of this biphasic response to ATP varied with the level of basal tone of the preparation at the moment of application of ATP. A smiliar biphasic action was obtained by prostaglandin (PG) E2 among the various active substances studied including acetylcholine, histamine, catecholamines and various types of PG. Indomethacin (0-1 mug m1(-1) and aspirin (30 mug m1(-1)) completely abolished the ATP-induced inhibitory response observed in the presence of histamine (10 muM). Polyphloretin phosphate (100 mug m1(-1)) also significantly depressed the inhibitory response to ATP or PGE2. It is concluded that the response to ATP of the preparation is mediated by PGE2 released via the stimulation of its biosynthesis.

Adenosine Triphosphate↗

Coeliac axis-oriented approach in surgery for advanced gastric cancer.

To achieve the systemic curative lymph node dissection in gastrectomy for advanced gastric cancer, coeliac axis-oriented approach was proposed. Mobilization of the spleen as well as the tail and body of the pancreas from the left retroperitoneum and Kocher's maneuver lifting up the hepatoduodenal ligament and head of pancreas from the right retroperitoneum permits the observation of the coeliac axis under direct vision and enables the para-aortic node dissection with ease. This approach was applied to 131 cases with advanced gastric cancer with neither mortality nor notable complication.

Aorta, Abdominal↗

Comparison of motor reactivity of the human colon cold-stored in different preservative solutions to carbachol and noradrenaline in vitro.

We have compared the reactivity to carbachol and noradrenaline of circular smooth muscle isolated from the human colon which was cold-stored at 4 degrees C in three different preservative solutions: Krebs bicarbonate solution (KBS), phosphate buffer solution (PBS) or minimum essential medium (MEM). Concentration-dependent contractions in response to carbachol were reduced in terms of both their sensitivity (pEC50) and reactivity (Emax), depending on the period of cold storage. The reduction was more marked when the tissue was cold-stored in either MEM or KBS than in PBS. Similar reduction of the relaxation response to noradrenaline was also observed after cold storage. It is concluded that the cold storage of surgically resected human colon in PBS for two to three days best preserved smooth muscle functions for pharmacological examinations.

Adult↗

Assessment of apoptosis in oesophageal carcinoma preoperatively treated by chemotherapy and radiotherapy.

Apoptosis, programmed cell death, was immunohistochemically determined in 55 samples of oesophageal squamous cell carcinoma using the BM1 Mab. Sections from patients not treated (group 1, n = 12) or preoperatively treated by chemotherapy (group 2, n = 11), radiation (group 3, n = 13) or both (group 4, n = 8), and 11 additional cases of high-grade dysplasia or early cancer were examined. Most of the apoptotic cells were BM1-positive and checked by TUNEL proved to be nick end positive. They accounted for 7 (11%), 19 (29%), 21 (32%) and 26 (38%) cells per field in those 4 groups respectively. Chemotherapy and/or radiation significantly increased the number of apoptotic cells as compared to controls (p = 0.029 and p = 0.029, respectively). To assess the implications of the oncogene expression in the apoptotic pathway, additional section stained with bcl2 and p53 were negative for bcl2 and were positive for p53 in 16 samples (37%). Overall, positive cases for p53 mutation showed a significantly decreased incidence of apoptotic cells (p = 0.03). These results suggest that in situ assessment of apoptotic response better correlates to the apoptosis induced by radiation than that by chemotherapy, that abnormalities of the p53 protein decrease the apoptotic response in oesophageal carcinoma, and that immunohistochemical analysis of p53 protein helps to determine the sensitivity to these anticancer agents.

Adult↗