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Biomedical subjects

H Moritoki

Publications and source records attributed to H Moritoki.

53 records · Page 3Linked to original sources
PubMed1979

Possible involvement of prostaglandins in the action of ATP on guinea-pig uterus.

ATP and other adenine derivatives, such as AMP and adenosine, at concentrations above 10(-6) M induced dose-dependent contractions of guinea-pig uterine strips. Treatment of the strips with nonsteroidal anti-inflammatory drugs, such as indomethacin, aspirin and phenylbutazone, at concentrations of 10(-6) to 10(-4) M irreversibly inhibited the contractions, without affecting those caused by acetylcholine and bradykinin. Arachidonic acid (10(-8)-10(-6) g/ml) and prostaglandins (E1, E2 and F2 alpha, 10(-9)-10(-7) g/ml) restored the inhibited uterine response to ATP, but the inhibition was reinstated on washing out of the arachidonic acid or prostaglandins. Furthermore, the prostaglandin antagonists polyphloretin phosphate (3 x 10(-5)-3 x 10(-4) g/ml) and SC 19220 (10(-6)-3 X 10(-5) M) selectively suppressed the action of ATP. In addition to the prostaglandin antagonists, 2,2'-pyridylisatogen, reported to be an ATP antagonist, at concentrations of 10(-6) to 3 x 10(-5) M selectively inhibited the response of uterine strips to ATP. These results suggest the involvement of prostaglandins in the actions of ATP and other adenine derivatives on guinea-pig uterine tissue and provide further evidence for ATP-stimulated prostaglandin formation in smooth muscle.

Adenine Nucleotides↗
PubMed1978

Effects of cholinesterase inhibitors on the spasmogenic action of acetate esters on rat uterus.

Acetate esters, such as phenyl acetate and aspirin, induced atropine-sensitive contractions of isolated uterus only when choline was present. These contractions were selectively and reversibly inhibited by carbamate-type cholinesterase inhibitors, such as neostigmine and eserine, and quaternary ammonium compounds, such as tetraethylammonium and decamethonium. After treatment with organophosphorus cholinesterase inhibitors, such as di-isopropyl fluorophosphate and tetraethyl pyrophosphate, the uterus failed to respond to the acetate esters, even when high concentrations of choline were present. The inhibition of the response of the uterus by organophosphates was effectively removed by pyridine-2-aldoxime methiodide. Pretreatment of the uterus with neostigmine or simultaneous addition of high concentrations of quaternary ammonium compounds prevented the inhibition by organophosphates. The inhibition produced by neostigmine was also reduced by simultaneous addition of quaternary ammonium compounds. These findings suggest that some esterase having an anionic site and an esteratic site, probably cholinesterase, may mediate in the uterine contractions induced by acetate esters in the presence of choline, and that inhibition by organophosphates, carbamates and quaternary ammonium compounds of cholinesterase activity in the preparation may impede the initiation of contractions by the acetate esters in the presence of choline.

Acetates↗
PubMed1978

Potentiation by dipyridamole of the inhibition of guinea-pig ileum twitch response caused by adenine derivatives.

The inhibition actions of adenosine and adenine nucleotides, such as ATP, AMP and cyclic AMP, on contractions of guinea-pig from ileum induced by transmural stimulation were potentiated by dipyridamole, whereas those of inosine, morphine and tetrodotoxin were not affected. Tritium activity, accumulated during incubation of the ileal segments with [3H]adenosine, was reduced by dipyridamole. The adenosine added was degraded to inosine and then hypoxanthine during incubation, with the ileal segments, thereby restoring the twitch response of the ileal segments. In the presence of dipyridamole, the degradation of adenosine and the recovery of the twitch response was retarded. Thus, dipyridamole may potentiate the inhibitory actions of adenosine and adenine nucleotides on the twitch response of the ileum by inhibiting both the accumulation and the degradation of adenosine.

Adenine Nucleotides↗
PubMed1977

Aspects of the spasmogenic effects of acetate esters on ileal smooth muscle.

Acetate esters, such as aspirin methylester, aspirin and resorcinol monoacetate, induced contractions of guinea-pig ileum. Their actions were selectively antagonized by atropine, but were not affected by ganglion blocking agents, conduction blockers, aging with cooling, anoxia or antihistaminics. On the other hand, N-acetates, such as acetanilide and p-acetaminophenol, and no contractile action on the ileum. These acetate esters thus seemed to have a cholinergic action, and not a direct action on muscle or other known specific receptors for endogenous active substances. The contractions induced by the acetate esters were selectively potentiated by low concentrations of choline, whereas those induced by acetylcholine, nicotine, 5-hydroxytryptamine and histamine were not. However, N-acetates did not induce the contractions even in the presence of choline. Organophosphorus cholinesterase inhibitors, such as diisopropyl fluorophosphate and paraoxon, selectively and irreversibly inhibited the actions of aspirin and N,O-diacetyl-p-aminophenol with or without choline. From these results, it is concluded that the acetate esters with or without choline act through the cholinergic system. However, their actions cannot be explained in terms of known mechanisms, such as acetylcholine release, cholinesterase inhibition or a direct muscarinic action. Therefore, the acetate esters, including phenyl acetate which was supposed to be a releaser of acetylcholine, seem to have a hitherto undescribed type of cholinergic action whose mechanism is unknown. It seems that organophosphate-sensitive esterase(s) in the preparation may be essential for initiation of the actions of the acetate esters with or without choline, but the mechanism of the effect of choline is unknown.

Acetates↗
PubMed1976

Effects of methylxanthines and imidazole on the contractions of guinea-pig ileum induced by transmural stimulation.

Methylxanthines (10(-5) to 10(-3)M) were found to increase the amplitude of contractions of guinea-pig ileum induced by transmural stimulation but to inhibit those induced by acetylcholine or histamine. The order of the abilities of methylxanthines to augment the contractile responses was theobromine greater than caffeine greater than theophylline. When the contractions were completely suppressed by reduction of the calcium content in the medium or by addition of cyclic AMP, methylxanthines restored the responses effectively, just as does addition of calcium. Methylxanthines also accelerated the release of acetylcholine from the ileum associated with stimulation. Imidazole (3 X 10(-5) to 10(-3) M) had an essentially similar effect to methylxanthines in potentiating the contractile responses and in augmenting the release of acetylcholine. The present results indicate that the potentiating effects of methylxanthines and imidazole are due to an action on the nerve terminals, not on the postsynaptic membranes or contractile elements. Therefore, it si concluded that theit potentiating actions are due to facilitation of the movement of calcium in the nerve terminals on excitation, resulting in increased release of acetylcholine, and are not due to the effect of cyclic AMP formed as a result of their inhibitory actions on phosphodiesterase.

Animals↗
PubMedDate not supplied

Possible association of decrease of ATP-induced vascular relaxation with reduction of cyclic GMP during aging.

The effect of aging on the ATP-induced relaxation of rat thoracic aorta was examined. Haemoglobin, methylene blue and NG-nitro L-arginine, and removal of the endothelium inhibited or reversed the relaxation induced by ATP. The relaxant response of the aorta to ATP was greatest in the preparations from 4-week-old rats. As the age of rats increased to 45 and 105 weeks, the concentration-response curve for ATP was shifted to the right with reduction of maximal relaxation. ATP elevated cyclic GMP levels. This action was endothelium-dependent and inhibited by methylene blue, haemoglobin and NG-nitro L-arginine. With an increase in age of the rats from 4 weeks to 45 weeks, ATP-stimulated cyclic GMP production was attenuated, and in the aorta from 105-week-old rats cyclic GMP level was no longer elevated by ATP. In contrast to the age-associated marked change in cyclic GMP levels, cyclic AMP production was not affected by aging. It is suggested that age-related changes in ATP-induced relaxation and cyclic GMP formation occur mainly at the level of the vascular smooth muscle. Alterations in soluble guanylate cyclase, at step(s) distal to the guanylate cyclase, or in cyclic GMP-phosphodiesterase might contribute.

Adenosine Triphosphate↗
PubMedDate not supplied

Role of endotoxin in L-arginine-induced relaxation of rat thoracic aorta mediated by muscle-derived nitric oxide.

The contribution of endotoxin to the L-arginine-induced relaxation of the endothelium-denuded rat thoracic aorta, which appears to be mediated by nitric oxide synthase in the vascular smooth muscle, was investigated. Special attention was paid to the time course of the phenomenon and its dependence on the concentration of endotoxin. In the absence of endotoxin, L-arginine induced scarcely any relaxation of the arteries. Treatment of the arteries with endotoxin initiated relaxation in response to 10 microM L-arginine with lag periods of 2-4 hours. The degree of relaxation increased on repeated applications of L-arginine, to reach a consistent level after several hours. Increase in the concentration of endotoxin shortened the lag period, enhanced the degree of relaxation and lowered the threshold concentration of L-arginine required to relax the arteries. In endotoxin-primed arteries, L-arginine, at concentrations necessary to induce relaxation, stimulated the cyclic GMP production. Prophylactic application of actinomycin D or dexamethasone, which inhibits the induction of nitric oxide synthase, prevented the induction by endotoxin of the L-arginine-induced relaxation and cyclic GMP formation. Polymyxin B, which inhibits the action of endotoxin, also prevented the development of the endotoxin-sensitized relaxation and the cyclic GMP formation induced by L-arginine. When the Krebs solution was prepared using deionized water, the amount of endotoxin in the reservoir was above the level required to initiate the L-arginine-induced relaxation and cyclic GMP formation. These results suggest that endotoxin triggered the time-dependent development of the L-arginine-induced relaxation by expressing nitric oxide synthase in the vascular smooth muscle.

Amino Acid Oxidoreductases↗