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Y Misu

Publications and source records attributed to Y Misu.

At least 55 records · Page 3Linked to original sources
PubMed1995

L-DOPA systems for blood pressure regulation in the lower brainstem.

We have explored probable neurotransmitter roles of L-3,4-dihydroxyphenylalanine (L-DOPA) in baroreceptor reflex and blood pressure regulation in depressor sites of the nucleus tractus solitarii (NTS) and the caudal ventrolateral medulla (CVLM), and in pressor sites of the rostral ventrolateral medulla (RVLM) in anesthetized rats. During microdialysis of these three areas, the basal L-DOPA release is in part tetrodotoxin (TTX)-sensitive and Ca2(+)-dependent, high K+ Ca2(+)-dependently releases dL-DOPA. L-DOPA microinjected (10-300 ng) dose-dependently produces postsynaptic depressor responses in the NTS and CVLM and pressor responses in the RVLM, and a recognition site for L-DOPA functions tonically to activate depressor neurons in the NTS and CVLM and pressor neurons in the RVLM. It is highly probable that L-DOPA is a neurotransmitter of the baroreceptor afferents terminating in the NTS, which is based on further findings such as (1) antagonism by a competitive L-DOPA antagonist against depressor responses to aortic nerve stimulation, (2) TTX-sensitive L-DOPA release by aortic nerve stimulation, (3) abolition of baroreceptor-stimulated L-DOPA release by bilateral sino-aortic denervation and (4) decreases in tyrosine hydroxylase (TH)- and L-DOPA-immunoreactivities without modifications of dopamine- and DBH-immunoreactivities in the left NTS and ganglion nodosum 7 days after ipsilateral aortic nerve denervation peripheral to the ganglion. In the NTS, GABA tonically functions to inhibit via GABAA receptors L-DOPA release and depressor responses to L-DOPA, whereas L-DOPA induces GABA release. Impaired TTX-sensitive neuronal activity to release L-DOPA in the NTS and enhanced TTX-sensitive neuronal activity including a decrease in decarboxylation of L-DOPA to dopamine and an increase in sensitivity of the recognition site to L-DOPA in the RVLM are relevant to the maintenance of hypertension in spontaneously hypertensive rats. Decreases in the contents of L-DOPA in the right CVLM 10 days after electrical lesion of the ipsilateral NTS suggest a 'L-DOPAergic' and monosynaptic relay from the NTS to the CVLM. L-DOPA seems to play major roles as a neurotransmitter for baroreceptor reflex and blood pressure regulation in the lower brainstem of rats.

Animals↗
PubMed1995

Opioid mu- and kappa-receptor mediate phospholipase C activation through Gi1 in Xenopus oocytes.

In the Xenopus oocytes expressing mu- or kappa-opioid receptors, agonist-induced currents were observed only when the oocyte was coinjected with Gi1 alpha RNA and pretreated with K-252a, a potent inhibitor of protein kinases. The evoked currents were abolished by intracellular injection of EGTA or inositol 1,4,5-trisphosphate and the current-voltage relationship revealed that they are mediated through typical calcium-dependent chloride channels. These findings suggest that the mu- and kappa-receptors mediate phospholipase C activation through Gi1 alpha, and that these receptor mechanisms including downstream signalings might be inhibited by phosphorylation in vivo in the Xenopus oocyte.

Animals↗
PubMed1995

Protein kinase C inhibitor potentiates the agonist-induced GTPase activity in COS cell membranes expressing delta-opioid receptor.

In COS-7 cell membranes expressing cloned delta-opioid receptor, [D-Ser2, Leu5]enkephalin-Thr6, an opioid delta-agonist, showed no significant stimulation of high-affinity GTPase, while this agonist binding showed a guanine nucleotide sensitivity. Significant stimulation of GTPase activity by this agonist was observed only when the cells were pretreated with 0.1 microM calphostin C, a protein kinase C inhibitor, and when this inhibitor was further added to the reaction mixture at 1 microM. These findings suggest that protein kinase C is involved in the heterologous desensitization of delta-opioid receptor in the cells.

Analgesics↗
PubMed1995

Altered tonic L-3,4-dihydroxyphenylalanine systems in the nucleus tractus solitarii and the rostral ventrolateral medulla of spontaneously hypertensive rats.

We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter in the central nervous system [Y. Misu et al. (1995) Adv. Pharmac. 32, 427-459]. L-DOPA as a probable neurotransmitter for the primary baroreceptor afferents tonically functions to mediate cardiodepressor control in the nucleus tractus solitarii and also tonically functions to mediate cardiopressor control in the rostral ventrolateral medulla of rats. We further attempted to clarify whether a transmitter-like L-DOPA system is altered in these areas of adult spontaneously hypertensive rats. By microdialysis in the left nucleus tractus solitarii area, the basal L-DOPA release was lower in spontaneously hypertensive rats than that in Wistar-Kyoto rats. This release was partially reduced by tetrodotoxin (1 microM) to the same absolute levels in the two strains. Tonic neuronal L-DOPA release is impaired in this nucleus of spontaneously hypertensive rats. This impairment is not secondarily due to decrease in formation or increase in decarboxylation of L-DOPA, since tyrosine hydroxylase activity was increased in spontaneously hypertensive rats, compared to Wistar-Kyoto rats, while no difference of L-aromatic amino acid decarboxylase activity was seen in the caudal dorsomedial medulla including the nucleus. L-DOPA (10-300 ng) microinjected into the nucleus produced dose-dependent hypotension and bradycardia. A maximum depressor response of spontaneously hypertensive rats to L-DOPA at higher doses was slightly greater than that of Wistar-Kyoto rats. On the other hand, in the left rostral ventrolateral medulla, the basal L-DOPA release was higher in spontaneously hypertensive rats than that in Wistar-Kyoto rats. This release was also partially reduced by tetrodotoxin to the same absolute levels in the two strains. Tonic neuronal L-DOPA release is enhanced in spontaneously hypertensive rats. This enhancement seems to include partially a decrease in decarboxylation of L-DOPA, since L-aromatic amino acid decarboxylase activity was decreased in spontaneously hypertensive rats compared to Wistar-Kyoto rats, while no difference in tyrosine hydroxylase activity was seen. L-DOPA (10-600 ng) produced dose-dependent hypertension and tachycardia. Importantly, a pressor response of spontaneously hypertensive rats to L-DOPA at lower doses was slightly greater than that of Wistar-Kyoto rats. L-DOPA seems to play a transmitter-like role in blood pressure regulation at levels of the nucleus tractus solitarii and rostral ventrolateral medulla in rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Supersensitization of neurochemical responses by L-DOPA and dopamine receptor agonists in the striatum of experimental Parkinson's disease model rats.

We studied the mechanisms of dopamine receptor agonist- and L-DOPA-mediated supersensitization in experimental Parkinson's disease model rats, by measuring in vivo acetylcholine (ACh) release, GTPase activities, and mRNA expression in the striatum of 6-hydroxydopamine-treated rats. D1 agonist (SKF38393) and D2/D3 agonists (bromocriptine and quinpirole) showed more potent stimulation or inhibitions on ACh release in the model rat than in the control. However, quinpirole-evoked stimulation of GTPase activity was enhance in the model rats, compared to the control, while there was no significant enhancement of the bromocriptine-evoked stimulation. On the other hand, L-DOPA at 0.3-10 pM showed a biphasic action including significant inhibition on the GTPase activity in the lesioned striatal membranes, but not in the control. In the RNAase protection assay, neither D1, D2, Gi1 alpha, GoA alpha nor Gs alpha mRNA expression in the model was significantly different from the control. These findings suggest that there is supersensitization of D1 and D2/D3 receptors in the experimental Parkinson's disease model, while the upregulation of their receptors or GTP-binding proteins (G-proteins) to be coupled to their receptors is unlikely involved in major parts of such mechanisms. In addition, the present report provides the first evidence that L-DOPA mediates neurochemical responses in the plasma membranes, possibly through its receptor.

Acetylcholine↗
PubMed1995

Pancreatic enzyme activity after a pylorus-preserving pancreaticoduodenectomy reconstructed with pancreaticogastrostomy.

This study was initiated to clarify whether the main hydrolytic enzymes of the pancreas are activated or inactivated when secreted into the stomach of patients who had undergone a pylorus-preserving pancreaticoduodenectomy (PPPD) and were given a pancreaticogastrostomy (PG) for the reconstruction. Seventeen such patients, 15 cancer patients and two pancreatic patients, who underwent PPPD-PG reconstruction were postoperatively followed up for 3 or more years to investigate the influence of the gastric acid on the p-type amylase and lipase activity. Results revealed that when the pH was < 3.0, both the p-type amylase and the lipase secretion remained inactivated, but when the pH was > 3.1, the activity of both enzymes increased proportionately. The pancreatic enzyme activity in the small intestine was also investigated in seven patients, six cancer cases and one case of pancreatitis, given a PPPD-PG reconstruction, and it was found that the pancreatic enzyme activity in the small intestine increased after milk loading. Further, the fecal pancreatic enzyme activity was investigated in 17 patients given a PPPD-PG reconstruction. Results reveal that the fecal p-type amylase, lipase, and chymotrypsin activity amounted to 21, 27, and 31% of the respective values seen in 10 healthy volunteers. However, the fecal pancreatic enzyme activity levels did not differ significantly from the levels seen in 20 pancreaticoduodenectomy patients given a pancreaticojejunostomy reconstruction. In conclusion, it was found that the main hydrolytic enzymes of the pancreas are activated when the gastric acidity is over pH 3.1, which normally occurs after ingestion of a meal.

Amylases↗
PubMed1995

Altered basal release and depressor effect of L-DOPA in the nucleus tractus solitarii of spontaneously hypertensive rats.

1. L-DOPA as a probable neurotransmitter of baroreceptor afferents functions as a tonic to mediate cardiodepressor control in the nucleus tractus solitarii (NTS). We attempted to clarify further whether a transmitter-like L-DOPA system is altered in NTS of adult spontaneously hypertensive rats (SHR). 2. By microdialysis of left NTS area, the basal L-DOPA release was lower in SHR than in Wistar-Kyoto (WKY) rats. This release was partially inhibited by tetrodotoxin (TTX, 1 mu mol/L) to a similar degree in both strains. TTX-sensitive L-DOPA release was lower in SHR than in WKY. 3. L-DOPA (10-300 ng) and L-glutamate (3-100 ng) microinjected into left NTS produced dose-dependent hypotension and bradycardia. No difference of responses to L-glutamate was seen in either strain. However, depressor but not bradycardic responses to L-DOPA at higher doses were slightly greater in SHR than in WKY. 4. In caudal dorsomedial medulla including NTS, tyrosine hydroxylase activity was increased in SHR compared to WKY, while there was no difference in either strain of L-aromatic amino acid decarboxylase activity. 5. Impaired tonic neuronal activity to release L-DOPA in NTS may be involved in the maintenance of hypertension in SHR. An increase in sensitivity of a recognition site for L-DOPA seems to occur as a compensatory mechanism for impairment of the neuronal activity.

Animals↗
PubMed1995

Altered basal release and pressor effect of L-DOPA in the rostral ventrolateral medulla of spontaneously hypertensive rats.

1. Transmitter-like L-DOPA functions as a tonic to produce postsynaptic cardiopressor responses in the rostral ventrolateral medulla (RVLM) of rats. We attempted to clarify whether a transmitter-like L-DOPA system is altered in the RVLM of spontaneously hypertensive rats (SHR) to maintain the hypertension. 2. By microdialysis of left RVLM area, the basal L-DOPA release was higher in SHR than in Wistar-Kyoto (WKY) rats. This release was partially inhibited by tetrodotoxin (TTX, 1 mu mol/L) to a similar degree in both strains. TTX-sensitive L-DOPA release was higher in SHR than in WKY. 3. L-DOPA (10-600 ng) and L-glutamate (10-300 ng) microinjected into left RVLM produced dose-dependent hypertension and tachycardia. Pressor but not tachycardiac responses to L-DOPA at lower doses were slightly greater in SHR than in WKY, whereas no difference to L-glutamate was observed in either strain. 4. In RVLM regions, there was no difference of tyrosine hydroxylase activity in SHR or WKY; however, L-aromatic amino acid decarboxylase activity was lower in SHR than in WKY. 5. Enhanced presynaptic neuronal L-DOPA release, including a decrease in decarboxylation and sensitization of postsynaptic pressor sites to L-DOPA in RVLM, may be involved in the maintenance of hypertension in SHR.

Animals↗
PubMed1995

Altered L-DOPA systems for blood pressure regulation in the lower brainstem of spontaneously hypertensive rats.

Recent findings have enhanced our understanding of the roles played by the L-DOPA system in the baroreceptor reflex and in blood pressure regulation in the lower brainstem. L-DOPA is probably a neurotransmitter of primary baroreceptor afferents terminating in depressor sites of the nucleus tractus solitarii (NTS). It also seems to be a neurotransmitter in depressor sites of the caudal ventrolateral medulla (CVLM) and in pressor sites of the rostral ventrolateral medulla (RVLM) of normotensive Wistar rats. We have explored whether or not presynaptic and postsynaptic functions of the L-DOPA system in these areas are altered to maintain hypertension in adult spontaneously hypertensive rats, as compared with age-matched Wistar Kyoto rats. In this review article, we survey the roles of the L-DOPA system in the baroreceptor reflex and in blood pressure regulation in the rat lower brainstem.

Animals↗
PubMed1995

Protein kinase C involvement in homologous desensitization of delta-opioid receptor coupled to Gi1-phospholipase C activation in Xenopus oocytes.

We have developed the coexpression system of both delta-opioid receptor (DOR1) and M2-muscarinic receptor (M2) which mediate agonist-evoked currents due to common post-receptor mechanisms including Gi1 and phospholipase C (PLC) activation in Xenopus oocytes reconstituted with Gi1 alpha. The DOR1-currents by 100 nM D-Ser2-leu-enkephalin-Thr6 (DSLET) were selectively desensitized by 10 nM phorbol 12-myristate 13-acetate (PMA). The PMA-desensitization of DSLET-currents was abolished in the presence of calphostin C, a protein kinase C inhibitor, or reversed by an intracellular injection of calcineurin, a protein phosphatase 2B. When a higher concentration (3 microM) of DSLET was used, DSLET-currents were rapidly desensitized by repeated challenges of DSLET itself. However, repeated challenges of 10 microM ACh caused no influence on such DSLET- or M2-currents. The desensitization of DSLET-currents was selectively reversed by protein kinase C inhibitors. Similar results were also obtained with various delta-opioid agonists. These results suggest that protein kinase C is involved in the homologous desensitization of delta-opioid receptors.

Animals↗
PubMed1994

Protein kinase inhibitor potentiates opioid delta-receptor currents in Xenopus oocytes.

In Xenopus oocytes injected with RNA coding for the delta-opioid receptor a small chloride current was evoked by [D-Ala2,Ser5]leucine-enkephaline-Thr6 (DSLET), a delta 2-opioid agonist. The evoked currents were rapidly reduced upon repeated challenges of DSLET. When Gil alpha RNA was co-injected into the oocyte, the evoked currents were increased 3.8-fold and became constant after at least three repeated challenges. In oocytes injected with RNAs coding for delta-receptor and Gil alpha, pretreatment with K-252a, a potent inhibitor of protein kinases, further potentiated the delta-receptor-mediated current responses, compared with those without the inhibitor. These results suggest that signalling involving the delta-opioid receptor is inactivated through in vivo phosphorylation in the Xenopus oocyte.

Analgesics↗
PubMed1994

6-OHDA-induced lesion of the nigrostriatal dopaminergic neurons potentiates the inhibitory effect of 7-OHDPAT, a selective D3 agonist, on acetylcholine release during striatal microdialysis in conscious rats.

Using striatal microdialysis, we attempted to clarify whether or not locally infused 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT), a selective D3 agonist, modulates the basal acetylcholine (ACh) release in conscious rats sham-operated and lesioned with 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. In the sham-operated rats, 7-OHDPAT at 1 microM decreased ACh release by 19% of control. In the 6-OHDA-lesioned rats, 7-OHDPAT (0.1-10 microM) decreased ACh release in a concentration-dependent manner. The decrease of 37% of control was seen at 1 microM 2 weeks after the lesion. The 7-OHDPAT (1 microM)-induced decrease was completely antagonized by 1 microM (-)-sulpiride, a D2 and D3 antagonist, while (-)-sulpiride at 1 microM alone failed to alter ACh release. There may exist intrastriatal D3 receptors to inhibit ACh release, and supersensitization is evident in a 6-OHDA-lesioned rat Parkinson's model.

Acetylcholine↗
PubMed1994

Species and age-dependent differences of functional coupling between opioid delta-receptor and G-proteins and possible involvement of protein kinase C in striatal membranes.

[D-Ser2,Leu5]-enkephalin-Thr6 (DSLET) and [D-Pen2,5]-enkephalin (DPDPE), both delta-agonists, stimulated the high affinity GTPase in the rat striatal membranes in a naltrindole-reversible manner. Similar stimulation was also observed in the striatal membrane preparations of 16-week-old guinea pigs, while not in those preparations of 4-week-old ones. When calphostin C, a protein kinase C inhibitor, was added to the reaction mixture, DSLET showed a marked stimulation in this activity in 4-week guinea pig striatal membranes. There was no effect of KT5720, a cyclic AMP-dependent protein kinase inhibitor, on such delta-opioid-mediated responses. These findings suggest that protein kinase C is locally involved in the functional uncoupling of delta-receptors to G-proteins in the striatum of young guinea pigs.

Aging↗
PubMed1994

Supersensitivity of quinpirole-evoked GTPase activation without changes in gene expression of D2 and Gi protein in the striatum of hemi-dopaminergic lesioned rats.

Quinpirole with D2 agonist activity showed a two-fold increase in the GTPase activity in the 6-hydroxydopamine-lesioned side of the striatum, compared with that in the control side. However, neither qualitative nor quantitative changes were observed in the gene expression of two alternative splicing products derived from dopamine D2 receptor gene or of Gil alpha, in the RNAase protection assay. These results suggest that D2 receptor-mediated supersensitization does not come from the D2 receptor upregulation.

Animals↗
PubMed1994

Supersensitization of intrastriatal dopamine receptors involved in opposite regulation of acetylcholine release in Parkinson's model rats.

Using striatal microdialysis, we studied effects of SKF 38393, a D1 agonist, and quinpirole, a D2 agonist, on the acetylcholine (ACh) release from the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rats by local infusion into the striatum. The present experiments clearly demonstrated evidence for the existence of intrastriatal D1 and D2 receptors regulating ACh release and for supersensitization of the striatal stimulatory D1 and inhibitory D2 receptor mechanisms in 6-OHDA lesioned rats.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Non-effective dose of exogenously applied L-dopa itself stereoselectively potentiates postsynaptic D2 receptor-mediated locomotor activities of conscious rats.

We attempted to clarify whether or not under inhibition of central dopa decarboxylase non-effective i.p. doses of L-dopa potentiate D2 receptor-mediated locomotor activities without conversion to dopamine in normal and i.v.t. 6-hydroxydopamine-treated rats. In normal rats, only the highest dose of quinpirole, a selective D2 agonist, at ranges used (0.01-1 mg/kg, s.c.) slightly increased the total counts of locomotor activities for 140 min after injection. A simultaneously injected non-effective dose of L-DOPA (30 mg/kg) potentiated locomotor activities by quinpirole (0.1 and 1 mg/kg). L-dopa potentiated quinpirole (1 mg/kg)-induced locomotor activities 90 to 140 min after the injection with marked increase in basal release of L-DOPA without increase in dopamine release simultaneously monitored during striatal microdialysis, compared to quinpirole alone. D-dopa (30 mg/kg) produced no potentiation. In 6-hydroxydopamine-treated rats, a non-effective dose of L-dopa (10 mg/kg) also potentiated quinpirole (0.3 mg/kg)-induced locomotor activities. L-dopa acting on a recognition site for itself stereoselectively potentiates postsynaptic D2 receptor-mediated locomotor activities of rats.

Animals↗
PubMed1994

Endogenously released L-dopa itself tonically functions to potentiate postsynaptic D2 receptor-mediated locomotor activities of conscious rats.

A non-effective dose of exogenously applied L-dopa itself stereoselectively potentiates postsynaptic D2 receptor-mediated locomotor activities of rats. We further attempted to clarify whether or not endogenously released L-dopa tonically functions to potentiate activities of these receptors, simultaneously monitoring locomotor activities and basal release of L-dopa and dopamine during striatal microdialysis in conscious rats. Quinpirole (1 mg/kg, s.c.) alone, a selective D2 agonist, increased locomotor activities and decreased basal L-dopa and dopamine release 20-140 min after injection. Pretreatment with alpha-methyl-p-tyrosine (3 mg/kg, i.p.), a tyrosine hydroxylase inhibitor, decreased locomotor activities and further decreased L-dopa release without modification of dopamine release, compared to quinpirole alone, whereas 3-hydroxybenzylhydrazine (100 mg/kg, i.p.), a central dopa decarboxylase inhibitor, further increased locomotor activities and markedly increased L-dopa release without modification of dopamine release. Endogenously released L-dopa itself functions tonically to potentiate activities of postsynaptic D2 receptors relevant to locomotor movement of rats.

Animals↗