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Biomedical subjects

E Munekata

Publications and source records attributed to E Munekata.

At least 73 records · Page 4Linked to original sources
PubMed1989

[Ala6]gastrin-releasing peptide-10: an analogue with dissociated biological activities.

COOH-terminal decapeptide of gastrin-releasing peptide (GRP-10) is a bombesin-like peptide, which has bioactivities to stimulate gastrin, insulin, and glucagon secretion. We have synthesized an analogue of GRP-10 that inhibits GRP-10's stimulation of insulin secretion both in vivo and in vitro and glucagon secretion in vivo, while potentiating the stimulation of gastrin secretion. The amino acid sequence of this peptide is H-Gly-Asn-Trp-Ala-Ala-Gly-His-Leu-Met-NH2 ([Ala6]GRP-10). Because the stimulation of insulin and gastrin secretion by GRP-10 has been ascribed to a direct effect on B- and G-cells, these findings suggest that there are two subtypes of receptors for bombesin-like peptides in mammalian tissues.

Animals↗
PubMed1989

Effects of neuromedin B on insulin and glucagon release from the isolated perfused rat pancreas.

The effect of neuromedin B (NMB) on insulin and glucagon release was studied in isolated perfused rat pancreas. Infusion of NMB (10 nM, 100 nM and 1 microM) did not affect the insulin release under the perusate conditions of 5.5 mM glucose plus 10 mM arginine and 11 mM glucose plus 10 mM arginine, although 10 nM NMB tended to slightly suppress it under the perfusate condition of 5.5 mM glucose alone. The degree of stimulation of insulin release provoked by the addition of 5.5 mM glucose to the perfusate was not affected by the presence of 10 nM NMB. The glucagon release was slightly stimulated by the infusion of 100 nM and 1 microM NMB but not by 10 nM NMB under the perfusate condition of 5.5 mM glucose plus 10 mM arginine. The effect of C-terminal decapeptide of gastrin releasing peptide (GRP-10) was also examined and similar results were obtained; 10 nM and 100 nM GRP-10 did not affect insulin release and 100 nM GRP-10 stimulated glucagon release under the perfusate condition of 5.5 mM glucose plus 10 mM arginine. The present results concerning glucagon release are consistent with the previous results obtained with isolated perfused canine and porcine pancreas. However, the results regarding insulin release are not. Species differences in insulin release are also evident with other neuropeptides such as substance P and the mechanism of such differences remains for be clarified.

Animals↗
PubMed1988

Effects of synthetic biologically active peptides on giant neurones identified in the left buccal ganglion of an African giant snail (Achatina fulica Férussac).

1. The effects of synthetic biologically active peptides, including Met-enkephalin, substance P, oxytocin, Arg-vasopressin, proctolin and FMRFamide, on the following four buccal neurones were examined: d-LBAN (dorsal-left buccal anterior neurone), d-LBMN (dorsal-left buccal medial neurone), d-LBCN (dorsal-left buccal central neurone) and d-LBPN (dorsal-left buccal posterior neurone). These peptides were examined at 10(-4) M. 2. Oxytocin excited d-LBAN and slightly excited d-LBCN, while this inhibited d-LBMN. Arg-vasopressin excited slightly d-LBAN and d-LBCN, but this had some times no effect. FMRFamide inhibited d-LBAN, and slightly inhibited d-LBCN. 3. No direct synaptic connection from the two ventral cerebral giant neurones, v-LCDN and v-RCDN, to the four buccal giant neurones was found, though the two cerebral neurones innervate the cerebro-buccal connectives.

Animals↗
PubMed1988

Further study of effects of synthetic peptides on identifiable giant neurones of an African giant snail (Achatina fulica Férussac).

1. Effects of the following peptides at 10(-4) M on identifiable giant neurones of Achatina fulica Férussac were examined: physalaemin, eledoisin, bradykinin, neurokinin A, neurokinin B, neuromedin B, gastrin releasing peptide decapeptide (neuromedin C), gastrin releasing peptide (14-27), cholecystokinin tetrapeptide, cholecystokinin octapeptide, thyrotropin releasing hormone, Arg-vasotocin, gamma-melanocyte stimulating hormone. 2. The six neurones tested were as follows: PON (periodically oscillating neurone), TAN (tonically autoactive neurone), RAPN (right anterior pallial neurone), d-RPLN (dorsal-right parietal large neurone), VIN (visceral intermittently firing neurone) and d-VLN (dorsal-visceral large neurone). 3. Of the peptides examined, only Arg-vasotocin at 10(-4) M produced the excitatory effects on PON, VIN and d-VLN. Physalaemin showed slight inhibitory effects on TAN; this substance was sometimes almost ineffective on the neurone. 4. The other peptides examined were completely ineffective on all of the neurones tested.

Animals↗
PubMed1988

Effects of neuromedin B, gastrin-releasing peptide-10 and their fragment peptides on secretion of gastrointestinal and pancreatic hormones in dogs.

The effects of neuromedin B (NMB), gastrin-releasing peptide (GRP)-10 and their C-terminal fragment peptides on the pancreatic and gastrointestinal hormone release were studied in dogs. Intravenous bolus injections of NMB and GRP-10 (4.5 nmol/kg) into conscious dogs elicited a sharp and statistically significant rise in plasma gastrin and insulin levels, but only GRP-10 brought on a significant rise in the plasma glucagon and enteroglucagon levels. The degree of stimulation of gastrin and insulin secretion by NMB and GRP-10 was dose-dependent. With a dose of 4.5 nmol/kg, the minimum size of C-terminal fragment peptides of NMB and GRP-10 to stimulate gastrin secretion was NMB and GRP-10, respectively. Both NMB and GRP-10 (0.1-100 nmol/l) stimulated insulin release from the isolated canine pancreas. The glucagon release was stimulated by 10 and 100 nmol/l GRP-10 and was not stimulated by the same doses of NMB. The somatostatin release was not influenced by either peptide. It is concluded that 1) NMB and GRP-10 can stimulate gastrin and pancreatic hormone secretion, and the latter effect may be mainly due to a direct action on the islet cells; 2) the stimulatory effect of GRP-10 is stronger than that of NMB. The difference in the minimal active fragment between NMB and GRP-10 suggests that the amino acid of position 3 - NMB (Leu) and GRP-10 (His) - may play an important role in their biological activity.

Amino Acid Sequence↗
PubMed1987

Behavioural effects of intrathecally injected tachykinins in rats with peripheral nerve transection.

The effect of unilateral sciatic nerve transection on behavioural responses produced by intrathecal administration of substance P (SP), neurokinin A, eledoisin and physalaemin was investigated in the rat. The injection of SP (3 nmol/rat) into the subarachnoid space was followed by reciprocal scratching, biting and licking of the fore- and hind-limbs. There was no observable difference in the behavioural response to SP between rats with nerve transection and sham operated rats at 5 days after operation. Whereas at 10, 20, and 30 days after nerve transection the response to SP was significantly increased as compared with sham operated rats. This phenomenon was also observed with neurokinin A (1.5, 3.0 and 6.0 nmol/rat), eledoisin (0.05 and 0.10 nmol/rat) and physalaemin (0.05 and 0.10 nmol/rat) at 10 days after operation. Ipsilateral depletion of SP from the lumbar (L4-L6) spinal cord was observed at 5, 10, 20, and 30 days after the unilateral transection of the sciatic nerve. These results suggest that sciatic nerve transection may produce an increased response to tachykinins through an enhanced sensitivity of tachykinin receptors in the lumbar cord.

Animals↗
PubMed1987

Behavioural assessment as substance P antagonists in mice.

A series of eleven undeca- and four hexapeptide antagonists of substance P (SP) have been assayed by the SP-induced behavioural test in mice. When 2 nmol of [D-Arg1, D-Pro, D-Trp, Leu]-SP (SP 1-11 I) was intrathecally injected together with SP (0.1 nmol), SP-induced response which consists of scratching, biting and licking was markedly inhibited. [D-Trp, Leu]-SP 6-11 (SP 6-11 I) given in a dose of 2 nmol was also inhibited the SP-induced response to the same degree as SP 1-11 I. Some of SP 1-11 or SP 6-11 analogues substituted with fluorine in positions 7 and/or 8 maintained the antagonistic effect of SP 1-11 I or SP 6-11 I, though the others were weaker. Intrathecal administration of SP 1-11 I and SP 6-11 I resulted in long-lasting antinociceptive effects as measured by the tail-flick test. Fluorine-containing SP analogues were less potent than the above two analogues in producing antinociception. These results suggest that the antagonistic effect of SP analogues on the SP-induced nociceptive response do not necessarily relate to antinociceptive activity at the spinal cord level.

Analgesia↗
PubMed1987

Effects of synthetic peptides on giant neurons identified in the ganglia of an African giant snail (Achatina fulica Férussac)--II.

Thirteen synthetic biologically-active peptides, which were classified into the peptides proposed as neurotransmitters in mammals and invertebrates and neural venom peptides, were investigated for their effects on the following six identifiable giant neurons of an African giant snail (Achatina fulica Férussac): RAPN (right anterior pallial neuron), INN (intestinal nerve neuron), RPeNLN (right pedal nerve large neuron), LPeNLN (left pedal nerve large neuron), d-LPeLN (dorsal-left pedal large neuron) and d-LPeCN (dorsal-left pedal constantly firing neuron). Oxytocin and proctolin at 10(-4)M excited the RAPN membrane potential, whereas FMRFamide at the same concentration inhibited the same neuron. FMRFamide at 10(-4)M markedly inhibited the d-LPeLN membrane potential, sometimes produced inhibition of RPeNLN and LPeNLN, showed varied effects (excitatory or inhibitory) on INN, and had no effect on d-LPeCN. The other peptides examined had almost no effect on any of the neurons tested.

Animals↗
PubMed1987

Effects of synthetic peptides on giant neurones identified in the ganglia of an African giant snail (Achatina fulica Férussac). IV.

1. The previous papers (Ku et al., 1986; Kim et al., 1987; Yongsiri et al., 1987) reported the effects of the synthetic peptides, i.e. Met-enkephalin, substance P, neurotensin, oxytocin, Arg-vasopressin, proctolin, FMRFamide, ranatensin C etc., on about 20 identifiable giant neurones of an African giant snail (Achatina fulica Férussac). 2. In the present study, the effects of the same peptides on the following Achatina neurones, other than those of the previous papers, were investigated: v-RPLN, v-LPSN, v-VNAN, v-VLN, r-VMN, l-VMN, v-l-VOrN and d-RCDN. 3. Of the neurones tested here, v-RPLN (ventral-right parietal large neurone) was excited slightly by Met-enkephalin, excited markedly by oxytocin, and inhibited by FMRFamide, at 10(-4) M. 4. Of these effects, those of oxytocin and FMRFamide were undoubtedly the direct effects on the neurone tested, whereas those of Met-enkephalin were probably due to the synaptic activations. 5. Another neurone, v-LPSN (ventral-left parietal large neurone), was affected by oxytocin and ranatensin C at 10(-4) M. The two substances sometimes showed similar simple excitatory effects, in other cases biphasic (excitation followed by inhibition) effects, and in a few cases almost no effect. 6. The rest of the neurones tested were not sensitive at all to any of the peptides examined.

Animals↗
PubMed1987

Stimulation of dog gastropancreatic hormone release by neuromedin B and its analogues.

The effects on gastrin, insulin, and glucagon release of neuromedin B (NMB), the C-fragment decapeptide of gastrin-releasing peptide-10 (GRP-10), seven analogues replacing amino acid positions 3, 6, and 9, and two C-terminal desamide analogues were examined in conscious dogs using intravenous bolus injection of these peptides study the structure-activity relationship of two bombesin-related peptides identified in mammals. The replacement from valine of position 6 of GRP-10 to threonine effectively reduced the stimulatory potency of these hormone secretions. Removal of the C-terminal amide of NMB and GRP-10 resulted in an almost complete loss of their stimulatory effect on gastrin secretion. [Leu3]GRP-10 elicited the most potent stimulatory activity on three hormone secretions among the analogues including NMB and GRP-10. These results indicate that valine in position 6 of GRP-10 and C-terminal amide of two peptides play an important role in the bioactivities of bombesin family peptides.

Amino Acid Sequence↗
PubMed1986

The contractile activities of neurokinin A, B and related peptides on smooth muscles.

The contractile activities of neurokinin A (NKA), neurokinin B (NKB) and related peptides on the guinea-pig ileum, rat vas deferens and rat duodenum were compared to the activity of substance P (SP). The potencies of NKA and NKB on the guinea-pig ileum (SP-P tissue) were nearly the same as that of SP. NKA was approximately 250-400 times more potent than SP on the rat vas deferens (EC50 = 59.5 nM; SP, EC50 = 1500 nM) and rat duodenum (EC50 = 1.8 nM; SP, EC50 = 674 nM) (SP-E tissues). NKB also showed high contracting activity on the rat duodenum (EC50 = 3.1 nM) but was 10 fold less active than NKA on the rat vas deferens. These results suggest that neurokinin peptides are possible endogenous agonists for the SP-E tissues. The contractile potency of NKA and NKB remained nearly complete after removal of N-terminal tripeptide portions, i.e., His-Lys-Thr and Asp-Met-His from the native peptides, respectively. However, the removal of the Asp residue from both NKA7 and NKB7 decreased activity until it was similar to that of SP.

Amino Acid Sequence↗
PubMed1986

Inhibitory effect of taurine on wet-dog shakes produced by [D-Ala2,Met5] enkephalinamide with reference to effects on hippocampal epileptic discharges.

The effects of taurine on wet-dog shakes produced by [D-Ala2,Met5]enkephalinamide (DAME) were investigated in rats. Wet-dog shakes and epileptic discharges in the hippocampus were produced by intraventricular administration of 50 micrograms of DAME. Pretreatment with 10 microliter of taurine, given intraventricularly in a dose of 0.95 mumol, inhibited wet-dog shakes and epileptic discharges in the hippocampus. While the same dose of gamma-aminobutyric acid (GABA) also inhibited the wet-dog shakes, the same dose of L-leucine did not suppress them. These observations indicate that the inhibition of DAME-induced wet-dog shakes by taurine is associated with the suppression of seizure activities in the hippocampus. The possibility that taurine possesses an antagonistic action on opioid peptides is discussed.

Animals↗
PubMed1986

Stoichiometry of actin and phalloidin binding: one molecule of the toxin dominates two actin subunits.

Sonication of F-actin in the absence of added ATP in the solvent induces denaturation of the actin. When phalloidin is added to actin at the molar ratio of 1:2, the denaturation is completely inhibited. More directly, pelleting experiments have indicated that the binding of phalloidin to actin subunits is saturated at the same molar ratio. The protection of F-actin from heat denaturation or depolymerization with 0.6 M KI is also complete with one molecule of the toxin over two actin subunits. Therefore, it is concluded that the binding ratio of phalloidin and the actin subunit is not 1:1 but 1:2.

Actins↗
PubMed1986

Immunoreactivity of a synthetic pentadecapeptide corresponding to the N-terminal region of the scrapie prion protein.

A pentadecapeptide with an amino acid sequence corresponding to the amino-terminal region of the scrapie prion protein was synthesized. Immunization of a rabbit with the peptide conjugated with ovalbumin induced specific antibodies. The antibodies reacted with all three of the major polypeptides in a proteinase K-treated fraction obtained from brains of mice infected with the Obihiro strain of scrapie agent. Some peptides in the proteinase-untreated fraction also shared antigenicity with the three major polypeptides. Specific polypeptides were also detected by the antiserum in a fraction prepared from spleens, but only two of the three major polypeptides were found and the amounts of the polypeptides were less than in brain.

Animals↗
PubMed1985

Effects of substance P and substance P-(6-11) on hormone release from isolated perfused pancreas: their opposite actions on rat and canine islets.

The effects of substance P (SP) and SP-(6-11) (SP6-11) on hormone secretion from the isolated perfused pancreas were compared in rats and dogs under the same conditions. In the rat, SP inhibited insulin secretion in a dose-dependent manner in a concentration range of 0.1-10 nM. Glucagon secretion was inhibited at a minimal dose of 10 nM SP. No significant effect on somatostatin secretion was obtained. SP6-11 exhibited the identical inhibitory potency as SP on both insulin and glucagon release from the rat pancreas. In the canine pancreas, by contrast, 1 and 10 nM SP and SP6-11, respectively, potentiated the release of insulin, glucagon, and somatostatin. Potentiation by SP6-11 was less than that by SP. These results demonstrate species differences in the effects of SP and SP6-11 on the release of pancreatic hormones.

Animals↗
PubMed1985

The distribution of corticotrophin-releasing factor immunoreactivity in various ovine tissues.

The presence of CRF in various ovine tissues has been quantified by a radioimmunoassay using an antibody raised against ovine CRF synthesized in vitro. Acetic acid extracts of ovine hypothalamus, cerebral cortex, cerebellum, pituitary and a number of visceral organs assayed in serial dilutions gave inhibition curves parallel to those of synthetic CRF. The highest concentration of CRF immunoreactivity (CRF-I) was found in the pituitary (84.6 +/- 8.77 ng/g wet weight) and the second highest in the hypothalamus (79.1 +/- 2.77 ng/g wet weight). CRF-I in the cerebral cortex and visceral organs (stomach, duodenum, jejunum, ileum, pancreas and liver) was about 60 and 30% of that in the hypothalamus, respectively. Chromatography of extracted CRF-I from these tissues on Bio-Gel P-10, equilibrated and eluted with 0.1 M acetic acid, revealed a single immunoreactive peak corresponding to synthetic ovine CRF. These findings indicate that CRF is generally distributed throughout ovine tissues including visceral organs, although its function remains to be clarified.

Adrenal Glands↗
PubMed1984

The excitatory action of the newly-discovered mammalian tachykinins, neurokinin alpha and neurokinin beta, on neurons of the isolated spinal cord of the newborn rat.

The actions of two new mammalian tachykinins, neurokinin alpha and neurokinin beta, were examined using the isolated spinal cords of newborn rats. Depolarizing responses of spinal motoneurons were recorded extracellularly from the lumbar ventral root during application of neurokinin alpha or neurokinin beta at concentrations ranging from 3 X 10(-8) M to 10(-6) M. The potencies of various tachykinins in depolarizing the motoneurons showed the following order: physalaemin greater than neurokinin beta divided by kassinin divided by substance P greater than neurokinin alpha. When the synaptic transmission in the spinal cord was blocked by tetrodotoxin, the depolarizing action of neurokinin alpha and neurokinin beta was markedly reduced but not completely abolished. The depolarizing action of neurokinin alpha and neurokinin beta was depressed by a substance P antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP. The possibility that neurokinin alpha and neurokinin beta act as neurotransmitters in the mammalian spinal cord is discussed.

Animals↗