Neuropeptide Y and its receptor antagonists. Use of an analog mixture-screening strategy.
Explore the source record for details and available documents.
Amino Acid Sequence↗
Biomedical subjects
K Tatemoto
Publications and source records attributed to K Tatemoto.
[Clinical and electrophysiological investigations of the influence of phenytoin natrium on tinnitus].
Anticonvulsant drugs like Carbamazepine and Phenytoin natrium (PHT) have been used for suppressing the tinnitus. In this paper, a clinical experience was reported, in that 100 patients with tinnitus were treated with intravenous administration of PHT, and the influence of PHT on auditory systems in the guinea pig investigated in detail electrophysiological examinations was also reported. The results are summarised as follows: 1. Clinical evaluation in the treatment of tinnitus (1) Of the 100 patients, more than 70% were well responded. (2) Pith match, loudness balance test correlated closely with the suppression of tinnitus. (3) Side effects were found in 5%, but there were all mild enough to be well tolerated. 2. Experimental evaluation in the guinea pig (1) In intravenous administration of PHT, latency and amplitude of each waveform peak in ABR were prolonged and decreased. As for the latency, waves III and IV were most prominently affected. The results may indicated that PHT works in the upper brain stem predominantly and effects also to the cochlear nucleus and cochlear nerve. (2) The amplitude of N1 in AP was depressed and its latency was slightly prolonged. These phenomena related closely with change of wave I in ABR. This may indicate that PHT can directly suppress the cochlear nerve. (3) Even at the dose that apparently influenced ABR and N1 in AP, no obvious change was observed on amplitudes in CM and EP, that may indicate PHT cannot affect on hair cells at this dose or it cannot proceed to the cochlea. (4) These changes were considered to be direct effect of PHT on auditory systems, since they were not correlated with change in the circulatory system. (5) In the perilymphatic perfusion of PHT, amplitudes in EP and CM were depressed slightly at the beginning of the perfusion. Changes in EP preceded those in CM. The results may indicate that PHT effects directly on the stria vascularis and secondarily on CM. (6) In this perfusion, no obvious change was found in AP. Nevertheless, the amplitude of N1 in AP increased over the initial level after the perfusion corresponding to the recovery of EP in some animals. The results may indicate that PHT cannot work directly on hair cells nor cochlear nerve and that the suppression of efferent inhibitory neurons can increase AP potentials. (7) PHT works on the large part of auditory pathway without cochlea, as a role of inhibitor. Considering antitinnitic effect of PHT, tinnitus bases on unusual excitement of the auditory pathway.
Adult↗
Novel peptide pancreastatin: its occurrence and codistribution with chromogranin A in the central nervous system of the pig.
The distribution of pancreastatin immunoreactivity was investigated in porcine brain, spinal cord, dorsal root ganglia, and pituitary. In the brain, immunoreactive cell bodies were present in many areas including the cortex, basal ganglia, hippocampus, thalamus, hypothalamus, mesencephalic reticular formation, cerebellum, and medulla oblongata. Immunoreactive fibres were most abundant in the globus pallidus, stria terminalis, entopeduncular nucleus, hippocampus, and in the substantia nigra. In the spinal cord, immunoreactive cells were found in laminae IV-IX. Immunoreactive fibres were concentrated in the dorsal horn. Pancreastatin immunoreactivity was localised to fibres and small cells (5-10% of the total) in the dorsal root ganglia. In the posterior pituitary, many immunoreactive fibres were present and in the anterior lobe subsets of gonadotrophs and thyrotrophs were pancreastatin-immunoreactive. The localisation of pancreastatin showed a parallel distribution with chromogranin A. Coexistence of pancreastatin with calcitonin gene-related peptide (CGRP) immunoreactivity in cell bodies in the spinal cord, including motoneurones, and with CGRP or galanin immunoreactivities in dorsal root ganglion cells was also noted. The differential pattern of pancreastatin immunostaining was reflected in the extractable levels of peptide with highest concentrations in the cortex (55.8 +/- 6.0 pmol/g wet weight, mean +/- S.E.M.), thalamus (60.0 +/- 5.0 pmol/g), hypothalamus (54.4 +/- 6.5 pmol/g), and anterior pituitary (2,714 +/- 380 pmol/g). Characterisation of pancreastatin immunoreactivity in the hypothalamus and pituitary by gel permeation and high-pressure liquid chromatography revealed multiple molecular forms, one of which was indistinguishable from natural porcine pancreastatin. The widespread distribution of pancreastatin immunoreactivity suggests this peptide may play a part in several neuroendocrine, autonomic, somatic, and sensory functions, and its colocalisation with chromogranin A is consistent with a precursor-product relationship.
Animals↗
Isolation and characterization of a tumor-derived human pancreastatin-related protein.
A protein with pancreastatin-like immunoreactivity has been isolated and purified from liver metastasis of a patient with insulinoma. NH2-terminal sequence analysis in conjunction with the use of antibodies specific for the C-terminal structure of pancreastatin identified this protein as a 186-amino acid residue protein corresponding to human chromogranin A-116-301. Using a sensitive radioimmunoassay it was found that serum from the patient with insulinoma contains two peptide species; one comigrates with the 186-amino acid residue pancreastatin and the other the 48-residue pancreastatin.
Amino Acid Sequence↗
Intracranial microinfusion of pancreastatin elevates blood glucose, free fatty acids, and corticosterone in rats.
Pancreastatin, a novel peptide recently isolated from porcine pancreas, significantly inhibits insulin and somatostatin release and augments glucagon release from the isolated perfused rat pancreas. This implies a role for endogenous pancreatic pancreastatin in the regulation of blood glucose and free fatty acids, the two major metabolic fuels. Since many peptides have similar biological effects when administered centrally and peripherally, the effects of centrally administered pancreastatin on blood glucose and free fatty acids were examined in 3 studies. Corticosterone was also measured in two of these studies. Intraventricular microinfusion of pancreastatin significantly elevated blood glucose, free fatty acid, and corticosterone concentrations in a dose-related manner. None of these effects was seen after subcutaneous injection of the same doses. Centrally administered pancreastatin appears to produce its effects on glucose and free fatty acids through actions in the brain, and either the brain, the median eminence, and/or pituitary for corticosterone.
Animals↗
Pancreastatin inhibits insulin release from Rin m 5F cells: reversion by pertussis toxin.
Pancreastatin inhibited carbachol- but not forskolin- or GIP-stimulated insulin release from Rin m 5F cells. The inhibition induced by pancreastatin was dose-dependent, with an ED50 value of 4 nM, and reached a maximum (50% of inhibition) at 10(-7) M peptide. Pretreatment of cells with pertussis toxin abolished the inhibitory effect of pancreastatin on carbachol-induced insulin release. We suggest that pancreastatin exerts a direct inhibitory control on insulin release through a pertussis toxin-sensitive cAMP-independent pathway.
Carbachol↗
Effect of natural peptide YY on pancreatic secretion and cholecystokinin release in conscious dogs.
The effects of natural peptide YY on pancreatic secretion under different stimulatory conditions and on fatty acid-induced cholecystokinin release were examined in five conscious dogs with pancreatic and gastric fistulas. Intravenous infusion of natural peptide YY at 1 and 0.2 microgram/kg/hr caused 60 and 40% inhibition of secretin- and cholecystokinin-stimulated secretion, respectively, and 40-50 and 20-40% inhibition of intraduodenal oleate stimulated secretion, respectively. A significant but transient decrease in the plasma cholecystokinin level was observed in response to peptide YY under oleate stimulation. The present study demonstrates that peptide YY has a potent inhibitory effect on both exogenously and endogenously stimulated pancreatic secretion and has a mild suppressive effect on fatty acid-induced cholecystokinin release suggesting that this peptide is an important colonic inhibitor of pancreatic secretion.
Animals↗
Effect of pancreastatin on pancreatic endocrine function in the conscious rat.
We have studied the effects of pancreastatin on insulin and glucagon secretions in vivo in the conscious rat. Rats were prepared with a gastric fistula and with both external jugular veins cannulated. We found that an i.v. infusion of pancreastatin (1 and 10 nmol/kg/h) inhibited the plasma insulin response and increased the plasma glucose response to the intragastric infusion of glucose in a dose-dependent manner. Furthermore, the infusion of pancreastatin increased the plasma glucagon response to the i.v. infusion of arginine in a dose-dependent manner, and it inhibited the plasma insulin response. However, such an infusion of pancreastatin had no effect on the basal plasma glucose level, nor did it have any effect on plasma insulin and glucagon concentrations. Thus, it is suggested that in the rat, the newly discovered pancreastatin is a regulator of islet cell function.
Animals↗
Inhibitory effect of pancreastatin on pancreatic exocrine secretion in the conscious rat.
The effect of newly discovered pancreastatin on pancreatic secretion stimulated by a diversion of bile-pancreatic juice (BPJ) from the intestine was examined in the conscious rat. Exogenous pancreastatin infusion (20, 100 and 200 pmol/kg.h) inhibited pancreatic protein and fluid outputs during BPJ diversion in a dose-dependent manner. Pancreastatin did not affect plasma cholecystokinin (CCK) concentrations. Pancreastatin (100 pmol/kg.h) inhibited CCK-stimulated pancreatic secretion, but did not inhibit secretin-stimulated pancreatic secretion. Pancreastatin alone, however, did not affect basal pancreatic secretion. In contrast, pancreastatin (10(-10)-10(-7)M) did not suppress CCK-stimulated amylase release from isolated rat pancreatic acini. These results indicate that pancreastatin has an inhibitory action on exocrine function of the pancreas. This action may not be mediated by direct mechanisms and nor via an inhibition of CCK release. It is suggested that pancreastatin may play a role in the regulation of the intestinal phase of exocrine pancreatic secretion.
Amylases↗
Isolation and characterization of bovine pancreastatin.
Bovine pancreastatin, a 47 amino acid residue peptide, was isolated from the pancreas and the pituitary gland using a chemical method which detects its C-terminal glycine amide structure. The complete amino acid sequence of the pancreatic peptide is 74% homologous to that of porcine pancreastatin and is identical to bovine chromogranin A-(248-294), as deduced from its cDNA sequence. The sequence of the first 28 amino-terminal residues of the pituitary peptide was determined to be identical to the corresponding sequence of the pancreatic peptide. Since the pituitary peptide also contains the C-terminal glycine amide, it is therefore likely to be identical in structure to the pancreatic peptide. Thus, we conclude that bovine chromogranin A is the precursor of bovine pancreastatin. Synthetic bovine pancreastatin inhibited pancreatic exocrine secretion in a similar manner to porcine pancreastatin.
Animals↗
Effect of pancreastatin on pancreatic endocrine and exocrine secretion.
Pancreastatin is a novel peptide that was recently purified from extracts of the porcine pancreas. The present study shows that pancreastatin (10(-9)-10(-8) M) can stimulate release of insulin from both the isolated perfused rat pancreas and from cultured rat islet cells in the presence of a low, non-insulinotropic concentration of glucose (4.2 mM). Pancreastatin (10(-9) M) can also inhibit release of insulin stimulated by a high concentration of glucose (16.7 mM). Pancreastatin, at 10(-8) M, can enhance glucose (8.3 mM) induced release of insulin in the static islet cell incubation. In addition, pancreastatin (10(-9)-10(-8) M) can inhibit, in a dose-dependent fashion, cholecystokinin (CCK)-8 stimulated release of amylase from dispersed guinea pig pancreatic acini. Pancreastatin alone, however, did not affect basal release of amylase. Our study shows that pancreastatin can exert a direct effect on both pancreatic endocrine and exocrine secretion.
Amylases↗
Effects of porcine pancreastatin on postprandial pancreatic exocrine secretion and endocrine functions in the conscious rat.
The inhibitory effect of a newly discovered polypeptide, pancreastatin, on postprandial pancreatic exocrine secretions and endocrine functions was examined in the conscious rat with a chronic external bile, pancreatic and gastric fistula. The infusion of 100 and 200 pmol/kg/h of pancreastatin significantly inhibited meal-stimulated pancreatic secretion of fluid and protein but not bicarbonate in a dose-dependent manner. The infusion of 100 and 200 pmol/kg/h of pancreastatin increased plasma pancreastatin concentrations (mean +/- SE) up to 133.5 +/- 15.9 and 209.8 +/- 14.5 pM, respectively. However, the same doses of pancreastatin failed to inhibit postprandial insulin and gastrin releases and did not affect blood glucose levels. It is suggested that pancreastatin may be an inhibitor of postprandial pancreatic exocrine secretion. However, the doses used in the present study may not have been high enough to affect endocrine functions.
Animals↗
Characterization of galanin receptors in the insulin-secreting cell line Rin m 5F: evidence for coupling with a pertussis toxin-sensitive guanosine triphosphate regulatory protein.
The present work characterizes galanin receptors in the insulin-secreting pancreatic beta-cell line Rin m 5F and documents their regulation by guanine nucleotides. Binding of [125I]galanin to cell membranes was found to be temperature dependent, rapid, saturable, reversible, and highly peptide specific. Optimal steady state conditions were achieved after a 60-min incubation at 15 C. The concentration dependence of galanin binding determined by adding increasing concentrations of [125I]galanin indicated that galanin receptors were saturated at 2-3 nM peptide. Scatchard analysis revealed a single class of receptors, with a Kd of 0.3 nM and a binding capacity of 82 fmol/mg protein. Guanyl 5'-yl imidodiphosphate dramatically enhanced the dissociation of bound [125I]galanin. Some guanine nucleotides inhibited [125I]galanin binding to membranes with the following order of potency: guanyl 5'-yl imidodiphosphate greater than GTP = GDP. Other nucleotides had no effect. The effect of the guanine nucleotides was Mg2+ dependent, but Na+ independent, although Mg2+ ions alone (5 mM) slightly enhanced [125I]galanin binding, and Na+ ions alone (100 mM) induced a 60% decrease in the binding. Finally, overnight treatment of Rin m 5F cells with pertussis toxin (0.4 microgram/ml) dramatically reduced [125I]galanin binding to cell membranes. This was related to a 4-fold decrease in receptor affinity, with no change in binding capacity. In conclusion, for the first time evidence of the existence of galanin receptors on functional pancreatic beta-cells is presented. Also, other findings support the fact that galanin receptors are functionally associated with a pertussis toxin-sensitive GTP-binding protein mediating guanine nucleotide control of galanin binding.
Adenylyl Cyclase Inhibitors↗
Effects of pancreastatin on insulin and pancreatic polypeptide secretion in the dog.
Porcine pancreastatin (1.19 nmol) was administered into the peripheral vein (i.v.) or the third cerebral ventricle (i.t.v.) of dogs and its effect on the secretion of insulin and pancreatic polypeptide (PP) studied. Neither means of administration had any effect on basal and glucose-induced insulin or PP secretion. However, i.v. pancreastatin did inhibit the i.v. CCK-8-induced insulin but not PP release. Pancreastatin may thus play a role in the regulation of insulin secretion in the canine pancreas.
Animals↗
Comparative effects of mammalian pancreastatins on the pancreatic exocrine secretion.
We have reported that porcine pancreastatin inhibits cholecystokinin (CCK)-stimulated pancreatic exocrine secretion in conscious rats. In the present study, the effects of mammalian pancreastatins on exocrine pancreatic functions in rats were compared using synthetic pancreastatins (porcine, bovine, human, and rat). Rats were prepared with cannulae draining pure pancreatic juice and bile separately and a duodenal cannula to return bile-pancreatic juice to the intestine and with a jugular vein cannula. After 90-min basal collection of pancreatic juice, CCK-8 (100 pmol/(kg.h] was infused for 3 h with or without pancreastatins (100 pmol/(kg.h]. All pancreastatins significantly inhibited protein output at an equivalent molar potency. These results suggest that mammalian pancreastatins have the same biological activity of a comparable magnitude and exert a similar biological action on the exocrine pancreas.
Amino Acid Sequence↗
[A case of congenital laryngeal web with subglottic stenosis].
A severe case of congenital laryngeal web with subglottic stenosis was reported. The patient had weak crying after birth and stridor was noticed from one month old. He had tracheostomy at two month old and the incision of the web was attempted under laryngomicrosurgery with CO2 LASER, although the attempt failed due to combined subglottic stenosis. The "trough method" was applied at the age of one year. The web was incised and subglottic granulation including the excessive cartilaginous tissue was removed through a laryngotracheal fissure. A piece of silicone membrane was inserted between the vocal cords preventing from adhesion and a silicone tube stent was also inserted into the subglottic space and trachea to keep the laryngotracheal space open widely. After one month and a half, the silicon membrane and silicon tube were removed and a silicon T-tube was inserted instead of the silicon tube. The anterior wall of the laryngotracheal space was closed using a hinge flap. The patient can vocalize and does not complain of dyspnea at present, one year after the removal of the T-tube.
Humans↗
[Facial bone fracture--statistical analysis and clinical aspects].
We experienced 102 cases of facial bone fracture during 16 months of 1986 to 1987. These cases were analyzed statistically concerning causes, age and locations of the fracture. These fractures have increased rapidly in number. The causes were classified into three types; occurrence during sport, traffic accident and fighting, which were equal in number. There were 85% males and 15% females in the patient cohort, which were concentrated at the ages of 10-20 years. A large part of the fractures was mostly consisted of maxillo-facial components (95%). These trends were similar to the previous report of our clinic (1972-1979). On the other hand, not only severe dysfunctioning cases but also complicated cases increased in number, so that the several clinical aspects were reported. Case 1: 17-year-old male presented with retraction of left cheek caused by Rugby foot ball, whose malar bone was dislocated backward and anticlockwise, was treated with oroantral reduction and with the intermaxillary packing of silicon blocks. Case 2: 10-year-old boy with complaint of double vision occurred by head blow to right eye. Pure type blowout fracture of the orbital floor was presented, which was reconstructed by silicon plate from the incision of the lower eyelid. Case 3: 59-year-old male presented with 6 month history of diplopia and retraction of left eye ball, had been under the conservative care by an eye doctor. X-ray examination showed the intraorbital soft tissue was blown out into the ethmoidal sinus. However the transethmoidal reduction was performed, the result was not satisfactory.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[A case of adenocarcinoma of the nasal cavity associated with syndrome of inappropriate secretion of antidiuretic hormone(SIADH)].
An inappropriate antidiuretic hormone secretion (SIADH) has been recognized as the cause of hypotonic hyponatremia, and the occurrence of this syndrome, accompanied by an ADH-producing adenocarcinoma in the nasal cavity, is reported. In February, 1987, a 50-year-old male, showing sights of delirium, disorientation, and irritability was admitted to the hospital. The patient was observed to be healthy, except for a neck lymphnode metastasis that was present up to the time of his hospitalization. The hyponatremia was incidentally found, although dehydration or intravascular volume depletion were not noted. These neuropsychiatric symptoms were considered to be associated with hyponatremia due to SIADH. He had had a partial maxillectomy, a neck dissection, and irradiation to the nose and nasal cavity 32 months earlier, and then underwent a surgical resection of the neck metastasis; he had a total of 10 other operations before the onset of the symptoms. Upon initial inspection, since neither an intracranial invasion nor a brain metastasis was found, we diagnosed that his symptoms were due to an autonomic disturbance caused by surgical and mental "stress". When he died of cardiac failure due to a mediastinal invasion 8 months after the onset of SIADH, tumor tissues was extirpated in an autopsy and was then cultured. In this manner, it was proved that the tumor cells had been producing ADH. This procedure clarified that the syndrome had resulted from an ADH-producing tumor of the nasal cavity.
Adenocarcinoma↗