Biomedical subjects

N Yanaihara

Publications and source records attributed to N Yanaihara.

At least 19 recordsLinked to original sources

PubMed1992

Vasodilator action of guinea pig vasoactive intestinal polypeptide (VIP): comparison with common mammalian VIP.

The vascular activity of guinea pig (gp) and common mammalian (p) VIP were compared in anesthetized guinea pigs and dogs. In the guinea pig, intravenous injections of gpVIP and pVIP increased pancreatic blood flow and reduced the systemic arterial pressure and pancreatic vascular resistance in a dose-related manner. There were no significant differences in the vasodilator actions of these two VIPs, indicating that the overall cardiovascular actions of gpVIP and pVIP are similar in guinea pigs. In the dog, gpVIP, when given intra-arterially, was less potent (about 1/4) than pVIP in its action on femoral blood flow, suggesting that the blood vessels of the dog hind leg are more sensitive to its own VIP than to gpVIP. Oxidation of pVIP and gpVIP with H2O2 greatly reduced their vasodilator effects on the femoral arterial blood flow. The vascular effects were restored to control levels by reduction of the oxidized peptides with mercaptoethanol, which suggests that methionine residues of gpVIP and pVIP are important in the vasodilator effect on the femoral arterial bed in dogs.

Animals↗

PubMed1992

Evidence for specific N-terminal galanin fragment binding sites in the rat brain.

The existence and widespread distribution of specific [125I]galanin-(1-15) fragment binding sites in the rat brain was demonstrated by using [125I]galanin-(1-15) as a radioligand in quantitative receptor autoradiographical studies. These binding sites were also present in several areas lacking or having very few [125I]galanin-(1-29) binding sites, such as the dorsal hippocampal formation, the neocortex and the neostriatum. [125I]Galanin-(1-15) binding sites showed a high selectivity for the fragment, since galanin-(1-15) could displace 80% of the binding whereas porcine galanin-(1-29) could only displace 30%. The binding was saturable with a Kd of 0.63 +/- 0.02 nM and a Bmax of 15.3 +/- 1.7 fmol/mg in sections from the dorsal hippocampal formation. Thus, a new type of galanin receptor selective for N-terminal galanin fragments may exist in the rat brain.

Animals↗

PubMed1992

[Structure-function studies of galanin].

Galanin is widely distributed in the central and peripheral nervous system and exerts a variety of physiological effects. This review briefly describes the chemical structure, tissue distribution, physiological effects, receptors and structure-function relationships of galanin. It is worth noting that the inhibitory effect of newly synthesized galanin (1-15)-ol on guinea pig ileum contractions was of the same magnitude as that of galanin. This observation gives us an important clue as to the discovery of antagonists of galanin for neural systems.

Amino Acid Sequence↗

PubMed1992

Cardiovascular and respiratory actions of pituitary adenylate cyclase-activating polypeptides.

Effects of pituitary adenylate cyclase-activating polypeptide (PACAP38) and PACAP27 on the cardiovascular and respiratory systems were examined and compared to those of vasoactive intestinal polypeptide (VIP) in anesthetized beagle dogs. Intravenous PACAP27 and PACAP38 produced a decrease in mean arterial blood pressure (MBP), and an increase in both femoral arterial blood flow (ABF) and in frequency of respiration (FR) with a dose-dependent relationship between 10 and 300 pmol/kg. PACAP27 produced a dose-dependent increase in heart rate (HR) between 10 and 300 pmol/kg while PACAP38 induced tachycardia which was not dose-dependent. Administration of 300 pmol/kg PACAP38 and PACAP27 produced extreme hypertension after transient hypotension. PACAP38 produced severe bradycardia after transient tachycardia. The cardiovascular actions of PACAP38 were persistent compared to those of PACAP27. Intravenous injection of 10-300 pmol/kg VIP brought about hypotension, tachycardia and an increase in ABF and FR with a dose-dependent relationship. VIP, at 2000 pmol/kg, did not produce the biphasic response obtained by a large dose of PACAP38. The present studies demonstrate that PACAP partially possesses VIP-like cardiovascular and respiratory actions and that the C-terminal 11 amino acid residues of PACAP38 are presumably responsible for a prolongation of its actions.

Adenylyl Cyclases↗

PubMed1992

Effects of thyrotropin releasing hormone and its analogues on unconsciousness following head injury in mice.

We examined the effects of thyrotropin releasing hormone (TRH) and its analogues (DN-1417: gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide citrate; MK-771: L-pyro-2-aminoadipyl-histidyl-thiazolidine-4-carboxamide; TSII-37: H-Lys-Gln-His-Pro-Gly-Ser-OH) on arousal in head injured mice, an animal model of unconsciousness. TRH, DN-1417, MK-771 and TSII-37 were injected 10 min before the head injury. TRH, DN-1417 and MK-771 caused dose-dependent decreases in the time required for recovery of the righting reflex time and in the time from the head injury to the onset of spontaneous movement. TSII-37 had no effect, when compared with the control group. In terms of the minimum effective dose, TRH and DN-1417 were of similar potency, but MK-771 was about 30-fold stronger than TRH. Measurement of the cross-reactivities of these TRH analogues by radiolabeled receptor assay suggest that the structure-binding relationship is proportional to the structure-activity relationship.

Animals↗

PubMed1992

Localization of gastrin-releasing peptide (GRP)-like immunoreactivity in the lysosomal compartment of the trigeminal ganglion cells of the rat.

Cellular and subcellular localizations of gastrin-releasing peptide-like immunoreactivity (GRP-LI) were examined in the perikarya of trigeminal ganglion cells. By immunolight microscopy using semi-thin sections, GRP-LI was observed in almost all the neuronal somata with various intensity as granular profiles distributing widely in the cytoplasm. By immunoelectron microscopy using ultrathin frozen sections and protein A-gold, GRP-LI was found predominantly in rounded or oval membrane-bound structures which were 300-800 nm in diameter and displayed various electron-density and heterogenous contents. Double-labeling immunoelectron microscopy using antibodies for GRP and cathepsin L, a well-characterized lysosomal proteinase, clearly demonstrated that these GRP-immunoreactive intracytoplasmic structures were lysosomes. In contrast, GRP-LI was detected only occasionally in the large granular vesicles (100-200 nm in diameter). These findings strongly suggest that considerable amount of GRP or GRP-like peptide is subject to intracellular degradation in the lysosome rather than to the regulatory secretion pathway, and this is the reason why no fibers immunoreactive for GRP have been detected in the peripheral sensory field.

Animals↗

PubMed1992

Immunohistochemical demonstration of galaninlike immunoreactive nerves in the human pancreas.

Galanin, the newly discovered 29 amino acid-residue peptide, has been shown to suppress glucose-induced insulin secretion in experimental animals, but its presence and physiological role in the human pancreas have not been established. In this study, the occurrence and distribution of galanin immunoreactivity in the human pancreas was investigated by immunohistochemistry. In addition, the possible coexistence of galanin and vasoactive intestinal peptide immunoreactivity in neural elements of the pancreas was examined. In the human pancreas, galanin immunoreactivity was localized in numerous nerve fibers around glandular acini, ductules and blood vessels, and in a few nerve fibers within islets. Nerve cells with galanin immunoreactivity were frequently noticed. Immunostainings for galanin and for vasoactive intestinal peptide on serial adjacent sections of intrapancreatic ganglia showed the coexistence of the two immunoreactivities in a large proportion (73.3%) of nerve cells. These observations may provide a morphological basis for the possible neurotransmitter or neuromodulator role of galanin in the human pancreas.

Galanin↗

PubMed1992

Immunocytochemical survey of haloperidol-induced immunoreactive changes of [Met]enkephalin-Arg6-Gly7-Leu8 in the rat forebrain.

It has already been demonstrated that chronic treatment with the dopamine receptor blocker, haloperidol, results in an increase of proenkephalin-A-derived peptides in the caudate-putamen (CP). To examine this phenomenon at the cellular level, we used immunocytochemistry to investigate the effects of haloperidol on [Met]enkephalin-Arg6-Gly7-Leu8 (MEAGL) immunoreactivity in the rat forebrain. After daily haloperidol (5 mg/kg, IP, for 6 days) or haloperidol decanoate (70 mg/kg, IM, given once or twice) treatment, immunoreactive neurons appeared diffusely in the whole CP and in the core part of the nucleus accumbens (Acb) and less frequently in the outer shell part of the Acb and the cell-dense layer of the tuberculum olfactorium (TuO). Increase of MEAGL-immunoreactive fibers in the CP, Acb, and TuO was also detected after these treatments, a particularly prominent increase being found in the striopallidal terminals in the globus pallidus and ventral pallidum. Haloperidol or haloperidol decanoate had no effect on MEAGL immunoreactivity in the cerebral cortex, amygdala, or hypothalamus. Reserpine treatment (5 mg/kg, IP, for 6 days) caused similar effects on the dorsal and ventral striopallidal system, and the direct injection of 6-hydroxydopamine (10 micrograms/5 microliters) into the CP led to the appearance of MEAGL-immunoreactive neurons in accordance with the depleted dopaminergic terminal area. These findings suggest that haloperidol influences enkephalinergic neurons region specifically and that in the dorsal and ventral striopallidal enkephalinergic system haloperidol increases MEAGL immunoreactivity in cell bodies, fibers, and terminals by blocking intrastriatal dopaminergic neurotransmission.

Animals↗

PubMed1992

A new brain glucosensor and its physiological significance.

The concentration of fibroblast growth factor (FGF), which is found in cerebrospinal fluid (CSF), markedly increases after the start of feeding. Food intake was dose-dependently suppressed by picomole doses of FGF and facilitated by anti-FGF antibody. This suppression was caused by activation of protein kinase C in glucose-sensitive neurons in the lateral hypothalamus. In situ hybridization by use of cDNA showed that acidic (a)FGF was produced in ependymal cells. The ependymal cells released aFGF by responding to glucose increase in CSF after feeding. Released aFGF diffused into the brain parenchyma and was taken by neurons. Passive avoidance was significantly more reliable after aFGF infusion into CSF. Clamping cerebral arteries in the gerbil induced ischemia, which damaged neurons in the CA1 layer of the hippocampus. Pretreatment with aFGF prevented this damage. Thus, aFGF is not only the most potent substance yet found for the suppression of feeding, but it is also extremely effective as a neurotrophic and memory facilitating substance.

Animals↗

PubMed1992

Structural requirements of peptide YY for biological activity at enteric sites.

Peptide YY (PYY) is a colonic hormone consisting of 36 amino acids that is a potent inhibitor of pancreatic exocrine, gastric acid, and insulin secretion. The objective of the present experiments was to characterize the structural requirements of PYY for inhibition of pancreatic exocrine, gastric acid, and insulin secretion, using conscious dogs prepared with gastric and pancreatic fistulas. Intravenous administration of PYY-(1-36), PYY-(3-36), or PYY-(4-36) (400 pmol.kg-1 x h-1) inhibited cholecystokinin-8-stimulated (25 pmol.kg-1 x h-1) pancreatic exocrine secretion (P < 0.05); however, PYY-(1-10), PYY-(1-20), PYY-(6-36), PYY-(10-36), PYY-(13-36), PYY-(24-36), and PYY-(27-36) did not inhibit pancreatic exocrine secretion. Intravenous administration of PYY-(1-36), PYY-(3-36), or PYY-(4-36) (200, 400, 800 pmol.kg-1 x h-1) inhibited pentagastrin (0.5 microgram.kg-1 x h-1)-stimulated gastric acid secretion (P < 0.05), as well as 2-deoxy-D-glucose-stimulated insulin release (75 mg/kg) in a dose-related manner. PYY-(6-36), PYY-(13-36), and [Leu31, Pro34] neuropeptide Y did not inhibit either gastric acid secretion or insulin release. In the gastric acid and insulin secretion bioassays, PYY-(1-36) was significantly more potent than PYY-(3-36) and PYY-(4-36); however, in the pancreatic exocrine secretion bioassay, the inhibitory effects of PYY-(3-36) and PYY-(1-36) did not differ significantly. PYY-(4-36) was less potent than PYY-(1-36) on pancreatic exocrine secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Purification and properties of steroid sulfatase from human placenta.

Steroid sulfatase was purified approximately 170-fold from normal human placental microsomes and properties of the enzyme were investigated. The major steps in the purification procedure included solubilization with Triton X-100, column chromatofocusing, and hydrophobic interaction chromatography on phenylsepharose CL-4B. The purified sulfatase showed a molecular weight of 500-600 kDa on HPLC gel filtration, whereas the enzyme migrated as a molecular mass of 73 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The isoelectric point of steroid sulfatase was estimated to be 6.7 by isoelectric focusing in polyacrylamide gel in the presence of 2% Triton X-100. The addition of phosphatidylcholine did not enhance the enzyme activity in the placental microsomes obtained from two patients with placental sulfatase deficiency (PSD) after solubilization and chromatofocusing. This result indicates that PSD is the result of a defect in the enzyme rather than a defect in the membrane-enzyme structure. Amino acid analysis revealed that the purified human placental sulfatase did not contain cysteine residue. The Km and Vmax values of the steroid sulfatase for dehydroepiandrosterone sulfate (DHA-S) were 7.8 microM and 0.56 nmol/min, while those for estrone sulfate (E1-S) were 50.6 microM and 0.33 nmol/min, respectively. The results of the kinetic study suggest the substrate specificity of the purified enzyme, but further studies should be done with different substrates and inhibitors.

Amino Acids↗

PubMed1992

Role of tachykinins in the control of pancreatic secretion and circulation.

Tachykinins (TK) are family of peptides including substance P (SP), substance K (SK) and neuromedin K (NK) that have been found in the nerves of the gastrointestinal tract and proposed to act as neurotransmitters to affect the motor, secretory and circulatory functions of the gut, but little is known about their action on the pancreas. In this study three series of tests were carried out to determine the action of SP, SK and NK on pancreatic secretion in conscious dogs and amylase release from the dispersed rat pancreatic acini and to correlate the alterations in pancreatic secretory and circulatory effects of TK in anesthetized dogs. SP, SK and NK infused i.v. in graded doses (0.12-1.0 microgram/kg per h) in conscious dogs stimulated pancreatic protein outputs reaching, respectively, 38% and 23% of the maximal response to CCK (40 pmol/kg per h). HCO3- outputs were also significantly increased but the highest response did not exceed about 5% of secretin (328 pmol/kg per h) maximum. Cholinergic blockade by atropine abolished the pancreatic responses to tachykinins. When added at various concentrations (10(-11)-10(-7) M) to the incubation medium of rat dispersed pancreatic acini, SK, SP and NK increased in concentration-dependent manner the release of amylase from the resting pancreatic acini and augmented the enzyme release induced by CCK-8 and by urecholine. In anesthetized dogs infused with a background dose of secretin (82 pmol/kg per h), addition of SP, SK and NK caused an immediate and dose-dependent increase in the pancreatic blood flow, oxygen consumption and pancreatic secretion accompanied by a dose-dependent decrease in arterial blood pressure. This study shows that TK are potent pancreatic circulatory stimulants and moderate secretagogues both in vivo and in vitro, acting, at least in part, via cholinergic pathway.

Amino Acid Sequence↗

PubMed1992

Production of immunoreactive corticotropin-releasing hormone in various neuroendocrine tumors.

The concentrations of immunoreactive (IR) corticotropin-releasing hormone (CRH) in 218 neuroendocrine tumors were determined by CRH radioimmunoassay. The tumors examined were 86 pancreatic endocrine tumors (PET), 22 neuroblastic tumors (NBT), 26 carcinoid tumors (CA), 24 pheochromocytomas (PHEO), 40 small cell lung carcinomas (SCLC) and 20 medullary thyroid carcinomas (MTC). IR-CRH was detectable in 21 neuroendocrine tumors (10 PET, four NBT, three CA, two PHEO and two SCLC) at levels of 10-2,700 ng/g wet weight (9.6%). The 21 patients with these CRH-producing tumors showed no clinical symptoms suggestive of Cushing's syndrome. The levels of plasma IR-CRH extracted by immunoaffinity chromatography were < 7.5 pg/ml in five normal subjects and a patient with a neuroblastic tumor containing 55 ng/g wet weight IR-CRH, but in a patient with a thymic carcinoid tumor containing 1,000 ng/g wet weight IR-CRH, the plasma level was elevated to 180 pg/ml. This patient did not have Cushing's syndrome nor an elevated plasma adrenocorticotropic hormone (ACTH) level. The concentrations of nine peptides (growth hormone-releasing hormone, somatostatin, ACTH, calcitonin, gastrin-releasing peptide, glucagon, vasoactive intestinal peptide, neuropeptide tyrosine and pancreatic polypeptide) were determined in extracts of the 21 IR-CRH-producing tumors. Some of these peptides were frequently found to be produced concomitantly with CRH. The results indicate IR-CRH to be produced by various neuroendocrine tumors, but Cushing's syndrome, due to the CRH, to be very rare. The results also show that CRH-producing tumors produce multiple hormones.

Adenoma, Islet Cell↗

PubMed1991

Distribution of somatostatin- and neuropeptide Y-immunoreactive nerve fibers in the porcine female reproductive system.

The localization and distribution of somatostatin and neuropeptide Y were studied in the porcine female reproductive system with the indirect immunofluorescence technique. Somatostatin-immunoreactive nerve fibers were observed in different parts of the ovary and in the muscular membrane of the uterus as well as in the mesosalphinx. Somatostatin-immunoreactive neurons were detected in the inferior mesenteric ganglion. Neuropeptide Y immunoreactivity was present in a large number of nerve fibers distributed in different regions of the uterus, oviduct and ovary. The present results suggest that the porcine female genital organs receive innervation by somatostatin- and neuropeptide Y-containing nerve fibers, but their exact functional role remains to be established.

Animals↗

PubMed1991

Effects of porcine galanin on the mesenteric microcirculation and arteriolar smooth muscle in the rat.

The actions of porcine galanin on the mesenteric circulation at the arteriolar level and on the isolated mesenteric small artery were studied in the rat. Male Wistar rats were anesthetized then laparotomized. Microscopic observation of the mesenteric microvascular area was made with a video camera and changes in arteriolar diameter were measured continuously with a width analyzer. Galanin (0.03-300 pmol), given intra-arterially into the mesenteric arteriole, caused an intermittent interruption of blood flow within 40 s and finally stopped the blood flow within a few minutes. The diameter of arterioles was not changed or was slightly widened. Galanin also relaxed the preconstricted small mesenteric artery in an endothelium-independent manner. Furthermore, the relaxing action of galanin was not antagonized by glibenclamide, indicating that activation of ATP-sensitive K+ channels was not involved. The present results suggest that galanin plays a modulatory role in the mesenteric circulation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1991

Met5-enkephalin-Arg6-Gly7-Leu8-immunoreactive nerve fibers in the major salivary glands of the rat: evidence for both sympathetic and parasympathetic origin.

The localization of the proenkephalin A-derived octapeptide, Met5-enkephalin-Arg6-Gly7-Leu8 (MEAGL), was studied in the major salivary glands of Sprague-Dawley and Wistar rats with the indirect immunofluorescence method. MEAGL-immunoreactive nerve fibers were found around the acini, along intra- and interlobular salivary ducts and in close contact with blood vessels. In the parotid and submandibular glands tyrosine hydroxylase (TH) immunoreactivity was observed in nerve fibers around the acini, in association with intra- and interlobular salivary ducts and around blood vessels, while in the sublingual gland TH-immunoreactive nerve fibers were only seen around blood vessels. Parasympathetic neurons in submandibular ganglia contained MEAGL immunoreactivity. Moderate TH immunoreactivity was seen in some neurons of the submandibular ganglia. A subpopulation of sympathetic principal neurons in the superior cervical ganglion were immunoreactive for both MEAGL and TH. In the trigeminal ganglion, no MEAGL-immunoreactive sensory neurons or nerve fibers were observed. Superior cervical ganglionectomies resulted in a complete disappearance of TH-immunoreactive nerve fibers, while MEAGL-immunoreactive nerve fibers were still present in the glands. The presence of MEAGL immunoreactivity in neurons of both sympathetic superior cervical ganglia and parasympathetic submandibular ganglia and the results of superior cervical ganglionectomies suggest, that MEAGL-immunoreactive nerve fibers in the major salivary glands of the rat have both sympathetic and parasympathetic origin.

Animals↗

PubMed1991

Immunohistochemical localization of [Met5]enkephalin and [Met5]enkephalin-Arg6-Gly7-Leu8 in sympathetic and parasympathetic neurons and nerve fibers projecting to the rat submandibular gland.

The localization of [Met5]enkephalin, [Met5]enkephalin-Arg6-Gly7-Leu8, vasoactive intestinal polypeptide and tyrosine hydroxylase immunoreactivities was studied in the submandibular gland of adult Sprague-Dawley and Wistar rats using the indirect immunofluorescence technique. Immunoreactivities for [Met5]enkephalin and [Met5]enkephalin-Arg6-Gly7-Leu8, a proenkephalin A-derived octapeptide, showed identical distributions. A large number of enkephalin-immunoreactive nerve fibers were detected around secretory acini, along intercalated ducts, convoluted granular tubules, intra- and interlobular ducts, as well as in close contact with blood vessels. The submandibular ganglia contained several enkephalin-immunoreactive neurons and nerve fibers. In the superior cervical ganglion numerous enkephalin-immunoreactive neurons and nerve fibers were also detected. Immunohistochemical co-localization studies indicated that [Met5]enkephalin and [Met5]enkephalin-Arg6-Gly7-Leu8 immunoreactivities co-exist with vasoactive intestinal polypeptide in a subpopulation of neurons of the rat submandibular ganglia, in nerve trunks along the salivary ducts of the gland, and in nerve fibers around the acini. Uni- or bilateral superior cervical ganglionectomies for 1-4 weeks resulted in a complete disappearance of tyrosine hydroxylase immunoreactivity in the glandular parenchyma, while moderate tyrosine hydroxylase immunoreactivity was seen in some neurons of the submandibular ganglia. Abundant [Met5]enkephalin-Arg6-Gly7-Leu8-immunoreactive nerve fibers were still seen around the acini and blood vessels, as well as close to salivary ducts. These operations did not affect the [Met5]enkephalin-Arg6-Gly7-Leu8-immunoreactive neurons in the submandibular ganglia. Many principal neurons in the superior cervical ganglion contained both [Met5]enkephalin-Arg6-Gly7-Leu8 and tyrosine hydroxylase immunoreactivity. Nerve ligation experiments indicated that [Met5]enkephalin-Arg6-Gly7-Leu8-immunoreactive sympathetic fibers project along the external carotid nerve. Accordingly, nerve fibers were found around the acini and blood vessels as well as in nerve trunks along the salivary ducts of the submandibular gland, showing co-localization of [Met5]enkephalin-Arg6-Gly7-Leu8 and tyrosine hydroxylase. Taken together, these observations suggest that the nerve fibers of the rat submandibular gland containing proenkephalin A-derived peptides are of both sympathetic and parasympathetic origin.

Animals↗

PubMed1991

Substance P-containing neurons innervating LHRH-containing neurons in the septo-preoptic area of rats.

Neuroanatomical attempts have been made to determine the synapses between luteinizing hormone-releasing hormone (LHRH)-containing neurons and substance P (SP)-containing neurons in the hypothalamus of female rats. Wheat germ agglutinin was injected into the septo-preoptic area (SPA) and found to be incorporated into certain SP-containing neurons within the arcuate nucleus and the ventrolateral portion of the anterior hypothalamus. Hence, we used a preembedding double immuno-staining technique in demonstrating LHRH and SP neurons in the SPA. In light-microscopic preparations LHRH was labeled with 3,3'-diaminobenzidine tetrahydrochloride (DAB) as chromogen while SP was labeled with silver-gold particles; brown LHRH cells appeared to be surrounded by black silver-gold dots. In electron-microscopic preparations, the labelings for LHRH and SP were made reversely; SP was localized with DAB chromogen, and SP-containing axonal terminals appeared to make synaptic contacts on silver-gold-labeled LHRH cell bodies and dendritic processes. The terminals contained numerous small clear vesicles and some large dense-cored vesicles, and the synaptic membrane specialization appeared to be symmetric and asymmetric. These findings indicate that certain SP neurons existing in the arcuate nucleus and the ventrolateral portion of the anterior hypothalamus may project fibers to make synaptic contact with LHRH neurons in the SPA in the rat.

Animals↗