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S Shioda

Publications and source records attributed to S Shioda.

At least 109 records · Page 6Linked to original sources
PubMed1997

Localization and gene expression of the receptor for pituitary adenylate cyclase-activating polypeptide in the rat brain.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a recently identified member of the secretin/vasoactive intestinal polypeptide (VIP) family. There are at least two types of receptor for PACAP: type I (PACAPR), which specifically binds PACAP; and type II (VIP/PACAPR), which binds both PACAP and VIP. The localization of PACAPR in the rat brain was determined by in situ hybridization and immunocytochemistry. We raised antisera against a synthetic peptide that corresponds to the carboxy-terminal cytoplasmic domain which is found in all subtypes of PACAPR in order to localize PACAPR-like immunoreactivity (PACAPR-LI) in the rat brain. In general, the distribution of PACAPR-LI correlated well with the distribution of PACAPR transcripts. Particularly strong PACAPR mRNA expression was detected in the olfactory bulb, hippocampus, cerebellum and hypothalamus and moderate labeling was detected in other scattered regions. At the cellular level, PACAPR-LI appeared to be concentrated predominantly in neuronal perikarya and dendrites. At the ultrastructural level, strong immunostaining for the PACAPR was found in plasma membranes, rough endoplasmic reticulum, cytoplasmic matrix, and at synapses. This study provides the basis for a better understanding of the functions of PACAP in the rat brain.

Animals↗
PubMed1997

Immunocytochemical localization of nicotinic acetylcholine receptor in the rat cerebellar cortex.

Although nicotinic acetylcholine receptors (nAChRs) have been reported to function in the cerebellar cortex, nicotinic acetylcholine receptor subtypes contributing to nicotinic currents in the cortex have not been well characterized at the subcellular level. This study deals with immunocytochemical localization of the nicotinic acetylcholine receptor alpha4 subunit using a monoclonal antibody against the alpha4 subunit. Alpha4-LI (alpha4-like immunoreactivity) was detected in the cell bodies of molecular, Purkinje cell and granular layers. In particular, the cell bodies of Purkinje cells were extensively immunostained. In Purkinje cells, alpha4-LI was found in perikarya mainly associated with rough endoplasmic reticulum, plasma membrane, and cytoplasmic matrix. At higher magnification, the immunoreaction product was densely localized along with somatic plasma membranes at the axo-somatic synapse and the plasma membranes at extrasynaptic regions of cell bodies. Alpha4-LI was also found in the axon terminals which form synapses with Purkinje cells. In the granular layer, somatic cell membranes of granular cells were immunostained. These morphological observations suggest that alpha4-containing nAChRs contribute nicotinic currents reported in Purkinje cells, and that presynaptic alpha4-containing nAChRs regulate the release of neurotransmitters on the axon terminals found near Purkinje cells.

Animals↗
PubMed1997

Nicotine increases cytosolic Ca2+ in vasopressin neurons.

Strong immunoreactivity for neuronal nicotinic acetylcholine receptor alpha4 subunit was detected in neurons of the supraoptic nucleus (SON). At the ultrastructural level, immunoreactivity for alpha4 was detected in the post-synaptic membranes as well as in the cytoplasmic matrices in the magnocellular neurons. Nicotine (1-10 microM) increased cytosolic Ca2+ concentrations ([Ca2+]i) in isolated arginine-vasopressin (AVP)-containing neurons in the rat SON. Nicotine (10 microM) was less potent in increasing [Ca2+]i in AVP-containing neurons than noradrenaline (1 microM), a known neurotransmitter in the SON. The nicotine-induced [Ca2+]i increase in AVP-containing neurons was markedly reduced when pre-treated with a protein kinase A (PKA) blocker, H89 (40 microM). These findings suggest that nicotine, a known neurotransmitter in the SON, activates AVP-containing neurons via nicotinic acetylcholine receptor which is linked to stimulation of cAMP-PKA-regulated Ca2+ signaling pathway.

Animals↗
PubMed1997

Isolation and structural characterization of pituitary adenylate cyclase activating polypeptide (PACAP)-like peptide from the brain of a teleost, stargazer, Uranoscopus japonicus.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel neuropeptide consisting of 38-residue (PACAP 1-38) and a truncated form with 27 residues (PACAP 1-27) that plays several roles in tetrapods. We isolated a highly purified PACAP-like peptide from the brain of a teleost, the stargazer, by extracting of acetone-dried powder with acetic acid followed by high-performance liquid chromatography (HPLC) on gel-filtration, cation-exchange, and reverse-phase columns. Purification was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting analysis using an anti-PACAP 1-27 antiserum. The PACAP-like peptide thus obtained had a molecular mass of 4,623, determined by mass spectrometry, and its amino acid sequence showed 89 and 87% identity with those of ovine and frog PACAPs, respectively. These results indicate that a PACAP-like peptide, which is a highly homologous with tetrapod PACAP, is present in the teleost brain.

Amino Acid Sequence↗
PubMed1996

Direct projections form catecholaminergic neurons in the caudal ventrolateral medulla to vasopressin-containing neurons in the supraoptic nucleus: a triple-labeling electron microscope study in the rat.

Direct projections form the A1 catecholaminergic cell group in the caudal ventrolateral medulla (CVLM) to arginine-vasopressin-containing (AVP-containing) neurosecretory neurons in the hypothalamic supraoptic nucleus (SON) were examined electron microscopically in the rat by a triple-labeling technique in which an anterograde tract-tracing method of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was combined with immunocytochemistry for tyrosine hydroxylase (TH) and that for AVP. In the SON, TH-like immunoreactive axon terminals which were labeled with WGA-HRP injected in the CVLM were in synaptic contact with neuronal profiles with AVP-like immunoreactivity. The results indicate that AVP-containing neurons in the SON receive monosynaptic catecholaminergic synaptic input from the CVLM.

Animals↗
PubMed1996

Transport of pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier and the prevention of ischemia-induced death of hippocampal neurons.

PACAP is a member of the secretin/glucagon/VIP family of peptides and demonstrates neurotrophic and neuroprotective effects at very low concentrations. We have previously shown that PACAP crosses the BBB to a modest degree by way of a saturable transport system. PACAP is transported across the BBB as an intact peptide to enter the parenchymal space of the brain. We tested the possibility that this modest rate of transport would be sufficient to produce the low levels of PACAP needed in the brain to exert a neuroprotective effect against ischemia. We found that PACAP given intravenously could indeed prevent the death of CA1 hippocampal neurons, even if the administration of PACAP was delayed for 24 h after the ischemic event. We suggest that iv PACAP could be neuroprotective after stroke, cardiac arrest, and hypotensive episodes.

Animals↗
PubMed1996

Current status of PACAP as a regulator of insulin secretion in pancreatic islets.

PACAP-27 and PACAP-38 as low as 10(-13) M stimulate insulin release from rat islets in a glucose-dependent manner. PACAP also glucose dependently increases cAMP and [Ca2+]i in rat islet beta cells. The [Ca2+]i and insulin secretory responses to PACAP exhibit a similar concentration-response relationship, exhibiting a peak at 10(-13) M. When the [Ca2+]i response is abolished by nitrendipine, a blocker of L-type Ca2+ channels, the insulin response is also inhibited. Insulinotropic peptides glucagon, GLP-1, and VIP also increase [Ca2+]i in beta cells, but only in the nanomolar concentration range. PACAP is 4 logs more potent that VIP, a peptide that exhibits 68% amino acid homology and shares the type II PACAP receptor with PACAP. Immunoreactivity for the type I PACAP receptor is demonstrated in rat islets. Furthermore, PACAP immunoreactivity is demonstrated in nerve fibers and islets in rat pancreas. Based on these findings, we can draw the following conclusions: (1) PACAP is localized in pancreatic nerve fibers and islets; (2) PACAP in the subpicomolar range stimulates insulin release from islets; (3) the stimulation of insulin release is mediated by the cAMP-dependent increase in [Ca2+]i in beta cells; (4) all the PACAP effects are glucose-dependent; (5) PACAP is the most potent insulinotropic hormone known, and (6) the type I PACAP receptor appears to mediate the action of PACAP in the subpicomolar range. Finally, we hypothesize that PACAP is a pancreatic peptide of both neural and islet origin and functions as an intrinsic potentiator of glucose-induced insulin secretion in pancreatic islets (FIG 6).

Animals↗
PubMed1996

Prevention of ischemia-induced death of hippocampal neurons by pituitary adenylate cyclase activating polypeptide.

Because neurons in the CA1 region of the hippocampus are vulnerable to forebrain ischemia, this model has been used for evaluating neuroprotective agents. We evaluated the 38-amino-acid variant of pituitary adenylate cyclase activating polypeptide (PACAP38), which had been previously shown to be neuroprotective in vitro against gp120-induced hippocampal neuronal death at concentrations as low as 0.1 pM. Ischemic death of rat CA1 neurons was prevented by infusing PACAP38 either intracerebroventricularly (1 pmol/h) or intravenously (16-160 pmol/h). Intravenous PACAP38 was effective even if the infusion was begun 24 h after ischemia. The results suggest that a concentration of PACAP38 in the brain which prevents the ischemic death of CA1 neurons can be reached by the systemic administration of a low dose of the peptide. The results are compatible with the previous reports that PACAP38 is transported from the circulation to the brain. Although the exact mechanisms remain to be determined, astrocytes in the CA1 subfield activated by ischemia appear to mediate the neuroprotection with PACAP38. These results are in contrast to those with other neuroprotective compounds and should be clinically important.

Animals↗
PubMed1996

The cDNA cloning of the hamster homologue of the human L6 gene.

The cDNA cloning and sequencing of a Syrian hamster gene that produces a surface antigen on cells transformed by the SV40 or BK virus are described. Sequence analysis showed that this gene is a member of the transmembrane 4 superfamily (TM4SF) and encodes the Syrian hamster counterpart of the human and the murine L6 antigens. The amino-acid sequences are highly conserved, being 71% identical among three species.

Amino Acid Sequence↗
PubMed1996

GABAergic synaptic innervation of catecholaminergic neurons in the area postrema of the rat.

Immunoelectron microscopy using the preembedding double immunostaining technique was applied to examine synaptic relationships between gamma-aminobutyric acid (GABA)-ergic neurons and catecholaminergic neurons in the area postrema of the rat. The catecholaminergic neuronal somata received only a few synapses from GABAergic axon terminals, whereas the catecholaminergic dendrites received many synapses from GABAergic axon terminals. Most of the synapses were symmetrical. GABAergic axon terminals could be found presynaptically to two catecholaminergic dendrites or both catecholaminergic and nonimmunoreactive dendrites. Conversely, a few catecholaminergic axon terminals were found presynaptically to GABAergic dendrites although such synapses were few. These findings suggest that in the area postrema, GABAergic neurons may modulate the functions of catecholaminergic neurons and may also be influenced by them.

Animals↗
PubMed1995

Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors: neuroendocrine and endocrine interaction.

The recent progress of research on the functions of pituitary adenylate cyclase activating polypeptide (PACAP), especially endocrine and neuroendocrine interactions, is described. Studies of the genes encoding the PACAP precursor and the type I PACAP receptor provide information on the control of PACAP gene expression and on the relationship between the structure of the receptor subtypes and the activation of various signal transduction pathways. The availability of specific antisera against PACAP and the type I PACAP receptor made it possible to examine their distributions in the brain and other tissues. Immunohistochemical studies and physiological studies with synthetic PACAP indicate that PACAP is a new type of hypophysiotropic hormone and also functions as a neurotransmitter, neuromodulator, and neurotrophic factor in the central nervous system. The abundance of PACAP and its type I receptors in the adrenal medulla and the results of studies with synthetic PACAP suggest that PACAP is a potent noncholinergic secretogue for catecholamines. PACAP and its receptors are also present in the pancreas and appear to play a regulatory role in insulin secretion at extremely low concentrations in a glucose-dependent manner. Immunohistochemical demonstration of PACAP and its receptors in the testicular spermatids at early stages suggests an important role of testicular PACAP in spermiogenesis. Together with its actions on pituitary gonadotropes, this suggests that it plays a key role in reproduction.

Amino Acid Sequence↗
PubMed1995

Immunocytochemical localization of nicotinic acetylcholine receptor in rat cerebral cortex.

Localization of nicotinic acetylcholine receptor (nAChR) alpha 4 subunits was investigated in rat cerebral cortex using a monoclonal antibody against alpha 4 subunits. The antibody depleted more than 70% of the [3H]methylcarbamylcholine choline binding activity of the solubilized membrane fraction. By light microscopy alpha 4-like immunoreactivity (alpha 4-LI) was found through layers II to VI. The immunostaining was the most prominent in cell bodies and apical dendrites of pyramidal cells in layer V. By electron microscopy most immunoreaction products were observed in the rough endoplasmic reticulum, cytoplasmic matrix and synaptic membranes. Alpha 4-LI was detected in the postsynaptic membranes of neuronal cell bodies and apical dendrites. These findings suggest that alpha 4-containing subtypes serve as one possibly the postsynaptic nAChR in rat cerebral cortex.

Animals↗
PubMed1995

Effect of hypophysectomy on pituitary adenylate cyclase-activating polypeptide gene expression in the rat testis.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the secretin/glucagon/vasoactive intestinal peptide (VIP) family. Our immunohistochemical and in situ hybridization histochemical studies indicated that PACAP-like immunoreactivity (PACAP-LI) and its mRNA were present in the germ cells in the rat testis. Because the testicular function is regulated by the pituitary gonadotropins, effect of hypophysectomy on the PACAP gene expression was investigated in the rat testis as an attempt to reveal the regulation of the testicular PACAP by the pituitary. The levels of testicular PACAP mRNA, which were determined by RNase protection assay, increased 2 weeks after hypophysectomy. In contrast, the levels of radioimmunoassayable PACAP decreased 2 weeks after the surgery. Immunohistochemistry showed that hypophysectomy did not change the distribution of PACAP-LI, although the number of immunopositive cells was markedly reduced after hypophysectomy. The replacement treatments of hypophysectomized animals with FSH or LH+FSH restored testicular PACAP mRNA to the levels in the control animals. On the other hand, all of these treatments (testosterone, LH, FSH, or LH+FSH) significantly increased radioimmunoassayable PACAP in the hypophysectomized rat testis. The results suggest that both testicular PACAP and its mRNA expression are regulated by the hypothalamic-pituitary-gonadal activity, and that FSH may play a major role in this regulation.

Adenylyl Cyclases↗
PubMed1995

The reciprocal synaptic relations between enkephalinergic neurons and catecholaminergic neurons in the area postrema.

A preembedding double immunostaining technique using antibodies against methionine-enkephalin and tyrosine hydroxylase was used to study synaptic relations between enkephalinergic and catecholaminergic neurons in the area postrema of the rat at the electron microscopic level. The large nuclei-containing cell bodies of the catecholaminergic neurons displayed well-developed Golgi apparatus. The catecholaminergic somata and dendrites received synapses from enkephalinergic axon terminals, and most of the synapses were symmetrical. Occasionally, the catecholaminergic axon terminals were also found to be presynaptic to the enkephalinergic dendrites. Because the enkephalinergic neurons have been reported to be involved in cardiovascular function and the catecholaminergic neurons involved in the vomiting behavior, the synapses observed in this study may provide morphological evidence of the relationship between the vomiting and cardiovascular functions that are triggered in the area postrema.

Animals↗
PubMed1994

Pituitary adenylate cyclase-activating polypeptide-like immunoreactivity in autonomic regulatory areas of the rat medulla oblongata.

Pituitary adenylate cyclase-activating polypeptide-like immunoreactivity (PACAP-LI) was mapped immunohistochemically in the rat medulla oblongata. We found the majority of perikarya with PACAP-LI in the visceral areas of the solitary nucleus, dorsal motor vagal nucleus, nucleus ambiguus, ventrolateral medulla, ventral medullary surface, and caudal raphe nuclei. Medium densities of labeled fibers were detected in the area postrema, solitary nucleus, dorsal vagal and raphe pallidus nuclei. Our morphological data support the hypothesis that PACAP is a central regulator of visceral functions.

Animals↗
PubMed1994

Oral malignant melanoma in Japan.

Clinical examination was performed on 20 cases of malignant melanoma in the oral region encountered at the First Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tokyo Medical and Dental University, during the 22-year period from 1970 to 1991. In addition, we reviewed 140 cases reported in the Japanese literature since the last major review in 1974. The results of our study revealed that the clinical course of malignant melanoma in the oral region is worse than oral squamous cell carcinoma and that treatment by radiotherapy is effective in prolonging the life of these patients. Clinically, the tumors were classified into five types: (1) pigmented nodular type; (2) nonpigmented nodular type; (3) pigmented macular type; (4) pigmented mixed type; and (5) nonpigmented mixed type. We suggest that oral malignant melanoma might be different from cutaneous malignant melanoma and that new criteria for diagnosis and therapy for oral disease should be considered.

Adult↗