[Opiate hypothesis of the origin of early childhood autism and sequelae for psychopharmacotherapy].
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Biomedical subjects
Publications and source records attributed to A Saria.
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Immunocytochemistry and a radioimmunoassay were used to investigate the existence and distributions of various regulatory peptide immunoreactivities (ir) in human submandibular and parotid glands. Numerous nerve fibers containing vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM), or neuropeptide tyrosine (NPY) and C-flanking peptide of NPY (CPON)-ir were found in close proximity to acini, ducts and blood vessels. Only a few calcitonin gene-related peptide (CGRP)- and substance P (SP)-ir nerve fibers could be demonstrated and were mainly localized around blood vessels and ducts. Galanin and the recently discovered peptides helospectin and pituitary adenylate cyclase activating peptide were unable to be detected in the salivary glands studied. Preliminary quantitative investigations of four human submandibular glands using radioimmunoassay showed that VIP-ir had the highest concentration, followed by NPY-ir and CGRP-ir; SP-concentrations were below the detection limit. The possible physiological significance of these peptides for salivary secretion is discussed.
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Sprague-Dawley rats were treated with bright light to induce retinal lesions and vasoactive intestinal polypeptide in the ventral tegmental area/substantia nigra was measured by radioimmunoassay. In Sprague-Dawley rats, but not in Brown Norway rats where light did not induce retinal lesions, significantly increased concentrations of vasoactive intestinal polypeptide were found 21 days after exposure with bright light. This increase declined to control values 60 days after the treatment. Our studies indicate that vasoactive intestinal polypeptide may be involved in visual neurotransmission and that the ventral tegmental area/substantia nigra may be connected to retinal input.
The first meeting of the European Neuropeptide Club was held in Igls (Austria) from Thursday to Saturday, January 23 to 26, 1991. Four sessions dealt with functional aspects of neuropeptides in the sensory, peripheral autonomic, gastrointestinal and central nervous systems. Recent results on drug developments towards peptide systems were also presented. This report summarizes 14 invited lectures and 25 oral communications. Additionally, 90 posters were presented, a number of them directly related to the topics presented by the invited speakers. Many posters supported or confirmed the findings mentioned in this report.
The effects of several heparin preparations on rat striatal neurokinin-1 receptor labelling were investigated. A low concentration of heparin dose-dependently stimulated [125I]Bolton-Hunter substance P ([125I]BH-SP) binding to rat striatal membranes. This effect was mainly due to an increase of the association velocity reflected by a decrease of the equilibrium dissociation rate constant. A higher heparin concentration inhibited specific [125I]BH-SP labelling by a negative allosteric mechanism as a result of an increase of the dissociation velocity.
Bilateral injection of endogenous tachykinins (substance P (SP), neurokinin A (NKA)) and selective neurokinin receptor ligands (senktide, [Sar9,Met(O2)11]SP, [MePhe7]NKB) into the substantia nigra reticulata increased striatal dopamine and serotonin metabolism. The increase in dopamine metabolism in the dorsal striatum at a low dose of the substances may be a direct effect on dopamine neurons in the substantia nigra reticulata via NK1 and NK3 receptors. The lack of effect at intermediate doses may be due to inhibitory mechanisms or desensitization. The changes after high doses in the dorsal and ventral striatum may be due to actions on dopaminergic neurons in the substantia nigra as well as in the ventral tegmental area, since there was considerable diffusion from the site of injection. An apparent rapid degradation of injected SP or NKA indicates that N-terminal SP fragments may participate in the SP response. The increased serotonin metabolism that occurs only at a high dose may involve all three neurokinin receptors.
The levels of various components of chromaffin granules were determined in rat adrenals after treatment with several stimulants. After reserpine the levels of calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and chromogranin B but not those of chromogranin A and secretogranin II were elevated. On the other hand, the mRNA of chromogranins A, B and secretogranin II were significantly increased. Treatment with oxotremorine or nicotine (multiple injections for 2 or 3 days) induced analogous changes for peptide and mRNA levels, however, the increases were smaller and for the mRNA less consistent. A single injection of oxotremorine or nicotine raised only the levels of CGRP and NPY and of the NPY mRNA whereas those of the chromogranins and their respective mRNAs remained unaltered. Amongst the membrane proteins only the levels of dopamine beta-hydroxylase are increased after prolonged stimulation, whereas those of cytochrome b-561, carboxypeptidase H and synaptin/synaptophysin (SYN) remain unaltered. Thus, the biosynthesis of chromaffin granules can be regulated in quite sophisticated patterns.
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The amygdaloid complex is an area with a high concentration of calcitonin gene-related peptide. In the present paper, immunohistochemical studies revealed a dense innervation of the central nucleus originating most probably from the bed nuclei of the stria terminalis. For determination of tissue concentrations of calcitonin gene-related peptidelike immunoreactivity, the amygdaloid complex was dissected into four parts. The distribution was found to be uneven with the highest concentration (1153.3 fmol/mg protein) in the portion including the nucleus amygdaloideus centralis. High performance liquid chromatographic analysis from an extract of amygdaloid tissue showed that 97% of the calcitonin gene-related peptidelike immunoreactivity measured by radioimmunoassay is authentic rat calcitonin gene-related peptide alpha or beta. Release of calcitonin gene-related peptidelike immunoreactivity was measured in superfused slices of amygdalae pooled from three rats. High potassium (60 mM) caused a significant release of calcitonin gene-related peptidelike immunoreactivity (from 0.88% of total tissue content to 1.91%) from the amygdaloid complex in vitro, which was blocked in calcium-free buffer. Pretreatment with haloperidol or clozapine caused a significant reduction of the 60 mM potassium-evoked release, compared with a saline treated control group (control 21.0 fmol; haloperidol 2.8 fmol; clozapine 8.8 fmol) and an increase of tissue levels after haloperidol treatment by 43%. These results demonstrate that calcitonin gene-related peptide is integrated in amygdaloid functions and possibly a target for actions of neuroleptic drugs.
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Sensory nerve stimulation by intragastric capsaicin (160 microM) prevents ethanol injury to the gastric mucosa and facilitates gastric mucosal blood flow (GMBF). The present study examined whether the capsaicin-induced increase in GMBF accounts for mucosal protection. Gastric perfusion of capsaicin (160 microM) in urethan-anesthetized rats did not change blood pressure but significantly enhanced GMBF as measured by hydrogen gas clearance. The same increase in GMBF was seen when capsaicin was administered together with an injurious concentration of ethanol (25%). GMBF was facilitated by capsaicin in a dose-related manner (10-640 microM), and the dose-dependent vasodilatation was significantly correlated with a dose-dependent reduction of gross damage to the mucosa. Histology showed that capsaicin prevented deep but not superficial mucosal damage. The vasodilator and protective effects of capsaicin resulted from stimulation of sensory neurons and propagation of nerve activity, since they were blocked after ablation of capsaicin-sensitive neurons or local intra-arterial infusion of tetrodotoxin. This and the finding of a limited access of intragastric capsaicin to the gastric wall indicates that the vasodilator and protective effects of capsaicin are mediated by a neural reflex. It is concluded that facilitation of GMBF is the major mechanism of sensory nerve-mediated prevention of gastric mucosal injury.
Various peptide immunoreactivities in the respiratory system have been reported, indicating complex physiological mechanisms. There is only little information on the upper respiratory system of man. The present study was carried out to demonstrate regulatory peptides in the nasal mucosa, larynx (vocal cords and ventricular folds) and soft palate of man using highly efficient immunocytochemical methods. In addition, some peptide immunoreactivities were measured by use of radioimmunoassay (RIA). Using indirect immunofluorescence and immunogold-silver staining (IGSS) with silver acetate autometallography, a series of peptides could be detected, including vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM), galanin, calcitonin gene-related peptide (CGRP), substance P, neuropeptide tyrosine (NPY), C-flanking peptide of NPY (CPON) and somatostatin. In addition, antibodies to protein gene-product (PGP) 9.5, neuron-specific enolase (NSE), S-100, PHE-5 and neurofilament proteins gave positive reactions in tissue sections. Using RIA, CGRP, substance P, and neurokinin A were measured. Our results demonstrate a complex network of regulatory peptide-containing nerve fibers and the possible existence of endocrine cells regulating various functions of the upper respiratory system, which need to be further investigated.
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