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Biomedical subjects

F Hata

Publications and source records attributed to F Hata.

At least 91 records · Page 5Linked to original sources
PubMed1993

Modulation of acetylcholine release from the myenteric plexus of guinea-pig ileum by 5-lipoxygenase metabolites of arachidonic acid.

Eicosatetraenoic acid, an inhibitor of 5- and 12-lipoxygenase, and AA861, a selective inhibitor of 5-lipoxygenase, dose dependently inhibited acetylcholine release from the myenteric plexus of guinea-pig ileum induced by electrical field stimulation. Metabolites of arachidonic acid produced by the 5-lipoxygenase pathway, such as 5-hydroxyeicosatetraenoic acid (5-HETE), leukotriene C4, D4 and E4, reversed the inhibitory effect of AA861. Among them, leukotriene D4 was the most potent, having an EC50 value of about 3 nM. The present study shows for the first time that 5-lipoxygenase metabolites may have a modulatory effect on acetylcholine release in the myenteric plexus of guinea-pig ileum.

Acetylcholine↗
PubMed1993

Role of prostacyclin in acetylcholine release from myenteric plexus of guinea-pig ileum.

The roles of metabolites of arachidonic acid in spontaneous and agonist-induced acetylcholine release from a longitudinal muscle preparation with myenteric plexus of guinea-pig ileum were studied. Indomethacin significantly decreased both spontaneous acetylcholine release and its release induced by nicotine and substance P. We had found that prostaglandin E2 (PGE2) partly reversed this inhibition. We now found that a stable prostacyclin analog, OP-41483 at 100 nM, completely reversed the inhibition of acetylcholine release by indomethacin. On the other hand, PGD2, PGF2 alpha and ONO-11113, a thromboxane A2 analog, did not have any significant effect on the inhibition by indomethacin. OP-41483 had no effect on acetylcholine release induced by nicotine or substance P in the absence of indomethacin. To confirm the modulatory role of endogenous prostaglandins on acetylcholine release, we also studied the release of 6-keto-PGF1 alpha, a metabolite of prostacyclin, and PGE2 from longitudinal muscle preparations. The preparations released appreciable amounts of 6-keto-PGF1 alpha continuously during the experiments. Indomethacin inhibited release, while nicotine did not affect it so significantly. Our results suggest that endogenous prostacyclin modulates acetylcholine release from cholinergic nerve terminals in the myenteric plexus of guinea-pig ileum.

Acetylcholine↗
PubMed1993

Mediators of nonadrenergic, noncholinergic inhibition in the proximal, middle and distal regions of rat colon.

1. The mediators of non-adrenergic non-cholinergic (NANC) relaxation of the longitudinal muscle of rat proximal, middle and distal colon were examined in vitro. 2. Electrical transmural stimulation (TMS) of proximal, middle and distal segments of rat colon induced NANC relaxations which were inhibited by tetrodotoxin (1 microM), but not by atropine (1 microM) or guanethidine (4 microM). 3. In the proximal colon, L-nitro-arginine (N5-nitroamidino-L-2,5-diaminopentanoic acid) inhibited the TMS-induced NANC relaxation and L-arginine (1 mM) reversed this inhibition. Nitric oxide (0.3-10 microM) induced relaxation of the proximal segment. 4. NANC relaxation of the proximal segments was still evident after desensitization to vasoactive intestinal peptide (VIP). A VIP antagonist (VIP 10-28, 10 microM) had no effect on the TMS-induced NANC relaxation, which was also resistant to alpha-chymotrypsin (2 units ml-1) and a substance P antagonist ([D-Pro2, D-Trp7,9]substance P, 1 microM). 5. In the middle colon, L-nitro-arginine did not inhibit the TMS-induced NANC relaxation in 6 of 9 preparations tested and partially inhibited the relaxation in the other 3 preparations. L-Arginine did not reverse the partial inhibition. 6. Complete desensitization to VIP was not achieved in the middle colon. The VIP antagonist had no effect on the TMS-induced NANC relaxation. After alpha-chymotrypsin treatment of the segment, desensitization of the segments to substance P, or in the presence of the substance P antagonist, the TMS-induced NANC relaxation was augmented. 7. In the distal colon, L-nitro-arginine did not have any significant effect on the TMS-induced relaxation and nitric oxide did not induce relaxation. The VIP antagonist significantly inhibited TMS-induced NANC relaxation. Alpa-Chymotrypsin-treatment of the distal segments resulted in significant inhibition of NANC relaxation. No desensitization to substance P was achieved. Treatment with the substance P antagonist had no effect. 8. These results suggest that nitric oxide is the mediator of the NANC inhibitory response in the proximal region of rat colon; in the middle colon, substance P acts as an excitatory neurotransmitter, antagonizing the NANC relaxation caused by the mediator of the response, which is still uncertain. Our results suggest that that VIP is the most likely candidate as a NANC transmitter in the distal colon.

Animals↗
PubMed1993

Dissociation of cyclic GMP level from relaxation of the distal, but not the proximal colon of rats.

The role of cyclic GMP (cGMP) in nonadrenergic, noncholinergic (NANC) relaxation of the longitudinal muscle of rat proximal and distal colon was examined. Electrical field stimulation (EFS) of preparations of longitudinal muscle from the proximal region significantly increased the cGMP content. Nitro-L-arginine inhibited this increase, and L-arginine reversed the inhibitory effect of nitro-L-arginine. Exogenously added nitric oxide (NO) and atrial natriuretic peptide (ANP) also increased the cGMP content of preparations of the proximal colon and induced muscle relaxation. From these and our previous findings suggesting an essential role of NO in NANC inhibition in the proximal colon, we conclude that the mechanism of NANC inhibition in the proximal region of rat colon involves NO and a cGMP generating system. In contrast, although exogenously added NO and ANP increased the cGMP content in the distal colon to the same extent as in the proximal colon, they did not induce any muscle relaxation. Vasoactive intestinal peptide (VIP), the most likely candidate as a NANC neurotransmitter in rat distal colon, did not increase the cGMP content in this region. Furthermore, no participation of NO in the NANC inhibitory response was observed in the distal region, but EFS increased the cGMP content significantly. Thus we conclude that relaxation of longitudinal smooth muscle in the distal portion of rat colon is not associated with a change in the cGMP content.

Animals↗
PubMed1992

Key roles of nitric oxide and cyclic GMP in nonadrenergic and noncholinergic inhibition in rat ileum.

Nonadrenergic and noncholinergic (NANC) inhibitory responses in circular and longitudinal muscles of the rat ileum were studied separately in vitro. Localized distension with a small balloon caused relaxation of the circular muscle on the anal side of the distended region. Nitro-arginine inhibited the relaxation and L-arginine counteracted the effect of nitro-arginine. Treatment of the preparation with superoxide dismutase (SOD) and methylene blue resulted in enhancement and inhibition, respectively, of the relaxation induced by distension. Nitric oxide caused relaxation of the circular muscle in a dose-dependent manner. 8-Bromo cyclic GMP (cGMP) caused relaxation of the circular muscle. Electrical transmural stimulation caused relaxation followed by a rebound contraction of the longitudinal muscle. Nitro-arginine inhibited the relaxation and L-arginine counteracted this inhibition. Similar results to those in the circular muscle were obtained in the longitudinal muscle with SOD, methylene blue, nitric oxide and 8-bromo cGMP. Electrical field stimulation increased the cGMP content of the longitudinal muscle preparation. Nitric oxide also increased the cGMP content of smooth muscle cells obtained from circular and longitudinal muscles of rat ileum. Preincubation of smooth muscle cells with methylene blue inhibited the effect of nitric oxide on the cGMP content. These results suggest a key role of cGMP in NANC inhibitory responses in rat ileum. The factors mediating the responses are discussed.

Animals↗
PubMed1992

Role of PGE2 in neurotransmission from pre- to post-ganglionic hypogastric nerves of guinea pigs.

The hypogastric nerve to guinea pig vas deferens was stimulated pre- or post-ganglionically by adjusting the position of the suction electrode. Both stimulations induced a biphasic contraction consisting of a rapid transient phase and a delayed tonic phase. Indomethacin partially inhibited the contraction induced by pre-ganglionic stimulation, but did not inhibit that induced by post-ganglionic stimulation. Prostaglandin (PG) E2 counteracted the inhibitory effect of indomethacin. Mepacrine also inhibited the contraction induced by pre-ganglionic stimulation. Arachidonic acid and PGE2 both reversed the inhibition. The PGE2-receptor antagonist SC-19220 inhibited the contraction induced by pre-ganglionic, but not post-ganglionic nerve stimulation. These results suggested that endogenous PGE2 is important in neurotransmission in the pelvic ganglion of guinea pigs.

Animals↗
PubMed1992

Role of cyclic AMP in prostaglandin-induced modulation of acetylcholine release from the myenteric plexus of guinea pig ileum.

Prostaglandins (PGs) have modulatory effects on spontaneous and nicotine-induced release of acetylcholine (ACh) from the myenteric plexus of guinea pig ileum. To determine whether cyclic AMP is involved in the mechanisms of these effects, we studied ACh release under conditions that inhibit PG synthesis. Indomethacin (IND), a cyclooxygenase inhibitor, inhibited ACh release concentration-dependently. The effect of the maximally inhibitory concentration of IND (2.8 microM) on nicotine-induced ACh release were reversed concentration-dependently by PGE2, forskolin, 3-isobutyl-1-methylxanthine (IBMX) and 8-bromo cyclic AMP. These compounds caused concentration-dependent reversal of the inhibition of spontaneous ACh release by IND, but their concentrations for restoration of spontaneous release were higher than those for restoration of nicotine-induced release. The effects of PGE2 and forskolin or IBMX were not additive in reversing the inhibition of nicotine-induced ACh release by IND. Neither forskolin nor 8-bromo cyclic AMP alone had any significant effect on either release. These results showed that increase in the level of cyclic AMP in myenteric cholinergic neurons restored ACh release from the tissue whose PG level had been lowered by IND and indicated that endogenous PGs may modulate the level of intraneuronal cyclic AMP.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Selective inhibitory effects of calcium channel antagonists on the two components of the neurogenic response of guinea pig vas deferens.

The effects of L-type calcium channel antagonists and omega-conotoxin on the contractile responses of guinea pig vas deferens were examined in vitro. Electrical stimulation of the postganglionic hypogastric nerve induced biphasic contraction consisting of rapid phasic and delayed tonic components. L-type calcium channel antagonists, such as diltiazem, verapamil and nicardipine, mainly inhibited the delayed tonic component, whereas omega-conotoxin mainly inhibited the rapid phasic component. Stimulations in the presence of prazosin and alpha, beta-methylene ATP induced rapid transient and delayed contraction, respectively, which were inhibited by omega-conotoxin and L-type calcium channel antagonists, respectively. Short-term stimulation with five pulses induced a small fast phasic contraction. This contraction, which could be desensitized by alpha, beta-methylene ATP, was inhibited by omega-conotoxin, but not by L-type calcium channel antagonists. At the concentrations used in the present study, none of the calcium channel antagonists inhibited the contractions induced by exogenously added ATP or norepinephrine. These findings suggest that L-type calcium channel antagonists and omega-conotoxin inhibit the neurotransmissions mediated by norepinephrine and ATP, respectively, from the postganglionic nerve to the vas deferens of the guinea pig. Inhibition of the voltage-dependent calcium channel is discussed in relation to the mechanism of cotransmission in this preparation.

Adenosine Triphosphate↗
PubMed1991

Prostaglandin E2 selectively affects purinergic transmission in guinea pig vas deferens.

The effect of prostaglandin E2 (PGE2) on the contractile response of the guinea pig vas deferens was examined. Postganglionic hypogastric nerve stimulation for 7 sec at 20 Hz induced a biphasic contractile response, consisting of fast phasic and delayed tonic components. Prostaglandin E2 delayed the onset and increased the maximum contractile responses. Stimulation in the presence of prazosin induced only a fast phasic contraction. Treatment with PGE2, in the presence of prazosin, delayed the onset of this response and increased its maximum. The delayed contraction, observed on stimulation in the presence of alpha,beta-methylene adenosine triphosphate (ATP), was enhanced moderately and concentration-dependently by PGE2. Short-term stimulation with 5 pulses induced a small fast phasic contraction. This contraction, which could be desensitized by alpha,beta-methylene ATP, was inhibited by PGE2 but not by prazosin. Prostaglandin E2 significantly enhanced the transient phasic contraction, induced by addition of exogenous ATP to the organ bath and had a similar but somewhat smaller effect on the tonic contraction induced by the addition of exogenous norepinephrine (NE). These findings suggest that PGE2 selectively delayed neurotransmission, mediated by ATP and enhanced contractions of the smooth muscle of guinea pig vas deferens, elicited by ATP or NE.

Adenosine Triphosphate↗
PubMed1990

Essential role of nitric oxide in descending inhibition in the rat proximal colon.

Possible mediators of descending inhibition in the rat proximal colon were studied. Localized distension with a small balloon caused relaxation of the circular muscle on the anal side of the distended region. This relaxation was still observed after the colonic segment had been desensitized to ATP, neurotensin and vasoactive intestinal peptide, so these compounds seem unlikely to mediate descending inhibition. Nitro-arginine inhibited the relaxation induced by the distension, and L-arginine counteracted the effect of nitro-arginine. Nitric oxide, isoamylnitrate and sodium nitroprusside caused relaxation. These results strongly suggest an essential role of nitric oxide in descending relaxation in the rat proximal colon.

Adenosine Triphosphate↗
PubMed1990

Effects of indomethacin and prostaglandin E2 on amylase secretion by rat parotid tissue.

Indomethacin increased the secretion by low concentrations of isoproterenol (IPR, 30-100 nM) and decreased the secretion by a high concentration of IPR (1 microM). Indomethacin also had opposite effects on the secretions induced by low and high concentrations of norepinephrine (NE). PGE2 did not affect the secretions induced by IPR and NE, but it reversed the stimulatory and inhibitory effects of indomethacin. These findings suggest that PG has a role in modulating the amylase secretory response of the rat parotid gland.

Amylases↗
PubMed1990

Differences in control of descending inhibition in the proximal and distal regions of rat colon.

1. Descending inhibition in the proximal and distal portions of rat colon was studied separately, in vitro. 2. In the proximal colon, localized distension with a small balloon caused three types of response (contraction; relaxation; relaxation, then contraction) of the circular muscle on the anal side of the distended region. 3. Distension caused descending relaxation of circular muscle in all segments of the proximal colon, although for this prostaglandin F2 alpha (PGF 2 alpha) was necessary in some segments to increase muscle tone. 4. Atropine and guanethidine did not inhibit this descending relaxation, but tetrodotoxin did. 5. Hexamethonium inhibited the descending relaxation in 14 of 17 preparations of proximal colon tested, but not in the others. 6. In the distal colon, distension consistently caused an increase in the tone of the circular muscles. Descending relaxation was observed only after development of higher tone. Atropine and guanethidine did not inhibit the relaxation, but tetrodotoxin did. 7. Hexamethonium did not inhibit the descending relaxation in most of the preparations of distal colon examined. 8. AF64A, an inhibitor of choline uptake, inhibited the response mediated by cholinergic neurons in vitro to electrical transmural stimulation of the longitudinal muscle of proximal colon. 9. Treatment of colonic preparations with AF64A in vitro resulted in inhibition of descending relaxation in those of proximal, but not those of distal, colon. 10. The participation of intrinsic cholinergic neurones in the descending neuronal pathway is strongly suggested by the results in the proximal colon, but less so in the distal colon. 11. The tone and spontaneous contractile activity of colonic circular muscles are discussed in relation to their neuronal control.

Animals↗
PubMed1990

Cooperation of ATP and norepinephrine in inducing contractile responses in guinea pig vas deferens.

Stimulation of the hypogastric nerve to the guinea pig vas deferens induced biphasic contraction consisting of a rapid transient phase (mediated by ATP) and a delayed tonic phase (mediated by norepinephrine, NE), whereas stimulations in the presence of selective antagonists caused each contractile phase separately. Stimulation in the absence of antagonist induced a larger rapid transient contraction than that induced by stimulation in the presence of alpha 1-antagonist. Results obtained in separate or simultaneous additions of exogenous ATP and NE showed synergism in the rapid transient contraction. These findings indicate that NE assisted ATP in inducing the hypogastric nerve-mediated contractile response in guinea pig vas deferens, but not vice versa.

Adenosine Triphosphate↗
PubMed1989

Fructose-related glycation.

We investigated in vitro the effect of the polyol pathway on the formation of advanced Maillard reaction products which have fluorescence and cross-links. Bovine serum albumin supplemented with various concentrations of glucose, fructose or sorbitol was incubated for 14 days. The fluorescence intensity was higher after incubation with fructose than after incubation with glucose. However, no significant increase in fluorescence intensity was found after incubation with sorbitol. These results suggest that in the polyol pathway fructose plays an important role in the formation of advanced Maillard products.

Fructose↗
PubMed1989

Re-evaluation of the stimulatory effect of norepinephrine on the secretion of amylase in the parotid gland of the rat.

The effect of the neurotransmitter norepinephrine(NE) in stimulating the secretion of amylase from the parotid gland of rats was studied by use of selective alpha- and beta-adrenergic antagonists. Its secretory response, mediated through beta-adrenoceptors, was slight during a short period of incubation, but rapidly increased after incubation for 10 min, showing a supersensitization phenomenon. Norepinephrine alone did not induce this phenomenon, but it induced the phenomenon in the presence of the alpha-adrenergic antagonist phentolamine or the alpha 1-antagonist prazosin. Isoproterenol-induced supersensitization was prevented by methoxamine. While, the accumulation of cyclic AMP in the tissue during incubation with isoproterenol and NE was not significantly affected by the presence of methoxamine and phentolamine, respectively. Phorbol dibutyrate did not inhibit the secretion induced by NE in the presence of phentolamine. These findings indicate that stimuli, mediated through alpha- and beta-adrenoceptors, induced secretion of amylase in parotid gland of the rat but that the alpha-effect inhibited the beta-effect when both stimuli were applied simultaneously and that the overall response of the tissue to NE resulted from the interaction of the two adrenoceptors.

Amylases↗
PubMed1989

Age- and diabetes-accelerated glycation in the human aorta.

The extent of glycation in pieces of human aorta was estimated by determining the content of furosine, which is derived from fructose-lysine through acid hydrolysis. Glycation of human aorta was found to increase with advancing age. A significant positive correlation was found between the degree of atherosclerosis and the furosine level in the aorta in subjects over 60 years of age. Furthermore, the furosine level in the aortae of diabetic patients was significantly higher than that in normal subjects of the same age. These results suggest not only that glycation in the aorta may increase with aging and with the development of arteriosclerosis, but also that diabetes may be related as well to premature aging as to arteriosclerosis.

Adult↗