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Biomedical subjects

E Brodin

Publications and source records attributed to E Brodin.

At least 19 recordsLinked to original sources
PubMed1992

Thyrotropin-releasing hormone (TRH)-like immunoreactivity in the grey monkey (Macaca fascicularis) spinal cord and medulla oblongata with special emphasis on the bulbospinal tract.

The distribution of thyrotropin-releasing hormone (TRH)-like immunoreactivity (LI) has been studied in the grey monkey (Macaca fascicularis) spinal cord and medulla oblongata by the use of indirect immunofluorescence and the peroxidase-antiperoxidase (PAP) technique. Furthermore, double-labeling experiments were performed in order to study colocalization of 5-hydroxytryptamine (5-HT)- and substance P-LI. A dense innervation of TRH-immunoreactive (IR) varicose fibers was found in the ventral horn motor nuclei, in the region surrounding the central canal, in the intermediolateral cell column, and in the dorsal horn laminae II and III. In addition, cell bodies harboring TRH-LI were found in the dorsal horn laminae II-IV. In the ventral horn, many of the large cell bodies and their proximal dendrites were totally encapsulated by TRH-IR fibers. From double-labeled sections a high degree of coexistence could be established between TRH-/5-HT-LI, TRH-/substance P-LI, and 5-HT-/substance P-LI in fibers in the motor nuclei; as a consequence, a large proportion of these fibers should harbor TRH-/5-HT-/substance P-LI. A coexistence between TRH-/5-HT-LI could also be demonstrated in the intermediolateral cell column. However, no unequivocal coexistence could be found between TRH-/substance P-LI and 5-HT-/substance P-LI in this region. In the dorsal horn, no clear coexistence could be encountered for any of the above indicated combinations. Electron microscopic analysis of material from the lumbar lateral motor nucleus demonstrated TRH-IR terminals making synapses with large cell bodies and dendrites. In addition, contacts lacking synaptic specializations could also be verified. In the medulla oblongata, with the use of the PAP technique, a large number of cell bodies containing TRH-LI were encountered in the midline raphe nuclei and in nucleus reticularis lateralis. A similar distribution pattern could be found for 5-HT-LI, but no cell bodies containing substance P-LI could be seen in these regions. Chemical analysis of specimens from cervical, thoracic, and lumbar spinal cord revealed higher concentrations of TRH- and 5-HT-LI in the ventral quadrants, whereas substance P-LI dominated in the dorsal quadrants. Thus, the concentrations of TRH-, 5-HT-, and substance P-LI was in accordance with the observed regional variation in density of IR-fibers and varicosities found in the spinal cord. We have shown that TRH-LI has a distribution in the monkey spinal cord and medulla oblongata similar to that previously demonstrated in other species.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Amphetamine regulation of mesolimbic dopamine/cholecystokinin neurotransmission.

The effects of acute and repeated amphetamine administration on mesolimbic dopamine (DA) neurons was assessed by studying DA and cholecystokinin (CCK) release in the nucleus accumbens (Acc), as well as effects on mRNA genes regulating DA and CCK synthesis in ventral tegmental area (VTA) cells in rats. Amphetamine (1.5 mg/kg) markedly increased extracellular levels of DA in the medial Acc (assessed by in vivo microdialysis) in drug-naive animals, about twice the amount released in animals repeatedly administered the drug for the previous 7 days (twice daily). CCK overflow was found to mirror the DA responses in that the very transient elevation of CCK monitored in drug-naive animals was attenuated in those with prior amphetamine use. The attenuation of both DA and CCK overflow in the medial Acc was found to be associated with a decrease in the number of CCK mRNA-positive VTA neurons (assessed by in situ hybridization histochemistry). Although the number of cells expressing CCK mRNA were decreased, the gene expression in those positive CCK and tyrosine hydroxylase mRNA cells in the VTA was significantly increased. The CCK mRNA neurons in the VTA were positively identified as those projecting to the medial Acc by the local perfusion of Fluoro-gold retrograde tracer via microdialysis probes located in the Acc.

Amphetamine↗
PubMed1992

Cholecystokinin is released from a crossed corticostriatal pathway.

The release of striatal cholecystokinin, glutamate, aspartate and dopamine was studied in vivo with microdialysis in decorticated rats, with or without callosotomy. Unlesioned rats were also analysed. Unilateral decortication produced a unilateral decrease in K(+)-stimulated extracellular striatal glutamate and aspartate levels, without decreasing cholecystokinin or dopamine levels. However, following decortication plus callosotomy, basal and K(+)-stimulated extracellular cholecystokinin and glutamate levels were significantly decreased in the striatum ipsilateral to side of decortication. Aspartate levels were bilaterally decreased. These results give evidence for the existence of crossed corticostriatal projections containing releasable cholecystokinin and glutamate.

Animals↗
PubMed1992

Short-term restraint stress and s.c. saline injection alter the tissue levels of substance P and cholecystokinin in the peri-aqueductal grey and limbic regions of rat brain.

Rats were exposed to short-term restraint (held by the tail for 1 min), injected s.c. with saline or subjected to the combination of these treatments. Fifteen and 30 min after these treatments the means serum corticosterone level was significantly increased by more than four times, compared to rats taken directly from their home cages, indicating a stress response. In the peri-aqueductal grey, the level of substance P-like immunoreactivity was increased by 45% (P < 0.01) and 65% (P < 0.01) 30 and 60 min after the combined treatment, respectively. Significant increases of the level of substance P-like immunoreactivity in the peri-aqueductal grey were also found after restraint only and after a s.c. saline injection. Similar, but less marked, changes in the level of cholecystokinin-like immunoreactivity in the PAG were also seen. In the accumbens a significantly decreased level of substance P-like immunoreactivity was encountered at 15 and 30 min after treatment, while the levels of cholecystokinin- and neuropeptide Y-like immunoreactivity were not significantly changed. In other regions studied, no effects on peptide levels were seen. The changes in peptide levels had a time course similar to that of the increase in serum corticosterone. Also the successive removal of rats from a common cage was found to increase significantly the serum corticosterone and the substance P-like immunoreactivity in the peri-aqueductal grey in the animals that were taken late in sequence from the cage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Adenosine A1 receptors mediate inhibition of tachykinin release from perifused enteric nerve endings.

A perifused preparation of guinea pig myenteric nerve varicosities (synaptosomes) was used to determine the characteristics of evoked tachykinin release and the inhibition of such release by adenosine analogues. Release of substance P-like immunoreactivity (SP-LI) and neurokinin A-like immunoreactivity (NKA-LI) was evoked by elevated extracellular [K+] in a reversible and repeatable manner. This release was completely abolished in the absence of extracellular Ca2+. Perifusion in the presence of 5'-N-ethylcarboxamidoadenosine (NECA), a nonselective A1/A2 adenosine receptor agonist, decreased K(+)-evoked release of SP-LI and NKA-LI compared with that in the absence of the nucleoside. Similar decrements in peptide release were obtained with N6-cyclopentyl adenosine (CPA), a selective A1 agonist, and 2-[p-(2-carboxyethyl)]phenethylamino-5'-N-ethyl-carboxamidoadenosi ne (CGS 21680), a selective A2 agonist. Response to all nucleosides was graded. Potency order of adenosine analogues was CPA greater than NECA much greater than CGS 21680. Inhibition due to the nucleosides was diminished in the presence of the highly selective A1-receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) while perifusion in the presence of DPCPX alone did not alter evoked release of either peptide. These findings provide direct measurements of inhibitory effects of adenine nucleosides on the release, from enteric nerve endings, of endogenous neuromediators SP and NKA. The findings also directly demonstrate the presence of functional adenosine receptors of the A1 subtype on enteric nerve endings coupled negatively to release of tachykinins. The presence of A2 receptors on enteric nerve endings is neither supported nor excluded.

Adenosine↗
PubMed1992

Dorsal column stimulation induces release of serotonin and substance P in the cat dorsal horn.

The neurohumoral mechanisms behind the pain-suppressing effect of dorsal column stimulation (DCS) still remain obscure. Experimental observations have indicated an inhibitory role for serotonin and, under certain conditions, also for substance P (SP), on nociceptive transmission in the spinal cord. Furthermore, some observations suggest that these substances might be involved in the effect of DCS. The present series of experiments was undertaken to investigate whether serotonin and SP are released in the dorsal horn by DCS. Twenty-one adult cats, in some experiments anesthetized, in others decerebrated at the midcollicular level, were used. Microdialysis probes were implanted bilaterally in lumbar dorsal horns (L5-L7) and perfused with Krebs' solution. Dialysates were analyzed for serotonin by high-performance liquid chromatography or for SP by radioimmunoassay. DCS was applied at the thoracolumbar junction with current parameters similar to those used clinically in humans. DCS induced a significant release of serotonin in the dorsal horn of decerebrated animals (173 +/- 83% increase; mean +/- standard error; n = 4; P less than 0.01), whereas the levels of the metabolite 5-hydroxyindoleacetic acid were not significantly influenced. In contrast, no release of SP could be recorded in response to DCS in the decerebrated preparation, although peripheral nociceptive stimulation (pinch) and noxious electric dorsal root stimulation induced an elevation of the SP levels. However, in intact animals DCS provoked a marked SP release in the dorsal horn (190 +/- 92% increase; n = 7; P less than 0.01). The release of serotonin and SP after DCS may indicate that these substances participate in the mediation of the pain alleviating effect of DCS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Diversity in tachykinin-like peptides in the insect brain.

When testing a large number of antisera against tachykinins of various vertebrates and one insect (the cockroach Leucophaea maderae) we found three distinct populations of tachykinin-immunoreactive neurons in the blowfly: (1) one recognized by antisera against substance P, (2) another by antisera against the frog peptide kassinin and (3) a third with antisera raised against the cockroach peptide Leucokinin I. As a comparison tests on the cockroach Leucophaea showed that only antisera against neurokinin A (NKA) and leucokinin I gave immunostaining, RIA and immunocytochemical displacement tests demonstrated that the each of the three listed types of antisera was specific for the corresponding antigenic peptide and showed virtually no cross reactivity with the other tachykinin peptides. By immunocytochemistry we have mapped the three populations of tachykinin-immunoreactive neurons in the blowfly CNS. Two constitute unique sets of interneurons that were previously not detected with other antisera, the third, recognized by antisera against substance P, is a subpopulation of the FMRFamide immunoreactive neurons. The leucokinin immunoreactive material in the blowfly seems to be chemically different from that in Leucophaea and also the sets of neurons immunolabeled in the two insect species are to some extent different. The preliminary results presented here indicate the presence of multiple forms of tachykinin-like peptides in the blowfly and that these are distinct from those in the cockroach. From the immunocytochemistry it appears that the insect tachykinins may be involved in a variety of regulatory functions in the CNS and in some cases possibly act as neurohormones.

Amino Acid Sequence↗
PubMed1991

Enhanced in vivo release of substance P in the nucleus tractus solitarii during hypoxia in the rabbit: role of peripheral input.

In the adult, pentobarbitone-anaesthetized rabbit, the in vivo release of substance P-like immunoreactivity was measured in the nucleus tractus solitarii using microdialysis and radioimmunoassay. Increased 160 +/- 16%) extracellular concentrations of substance P-like immunoreactivity were observed during hypoxic provocations of 9% O2 in N2 which also resulted in an increase in phrenic nerve activity. In bilateral carotid sinus nerve-denervated animals no enhanced release of substance P was seen in response to hypoxic challenges (105 +/- 6%) and the phrenic nerve activity was not significantly affected. Perfusion of the nucleus tractus solitarii region with the dopamine agonist, apomorphine (10(-5) M) resulted in a significant decrease in the extracellular level of substance P. These results provide further evidence that substance P is involved in the mediation of the hypoxic drive inputs from the peripheral chemoreceptors. The interactions of apomorphine with substance P release might also suggest a presynaptic modulation of substance Pergic neurons by dopamine in the nucleus tractus solitarii.

Animals↗
PubMed1991

Chronic treatment with SCH-23390, a selective dopamine D1 receptor blocker decreases preprotachykinin-A mRNA levels in nucleus tractus solitarii of the rabbit: role in respiratory control.

Acute intravenous administration of the selective D1 receptor blocker SCH-23390 resulted in an enhanced respiratory motor output as evidenced by the phrenic nerve activity, whereas local perfusion into the region of nucleus tractus solitarii had no effect. The increase in phrenic nerve activity was accompanied by a concomitant increase in the release of substance P in the region of nucleus tractus solitarii as measured by in vivo microdialysis technique. Chronic administration of SCH-23390 via subcutaneously implanted Alzet mini osmotic pumps, significantly decreased the level of preprotachykinin-A mRNA in the region of respiratory relay neurons in nucleus tractus solitarii but was without effect in the ventral medullary surface structure, wherein the central chemoreceptors are thought to be located. A smaller, but significant decrease was also seen in the striatum. The results suggest that chronic treatment with SCH-23390 leads to a disinhibition of an inhibitory dopaminergic input to the neurons in nucleus tractus solitarii from a suprapontine level, which may account for a subsequent inhibition of tachykinin-containing neurons in the nucleus tractus solitarii, the relay station for respiratory reflexes.

Animals↗
PubMed1991

Distribution of cholecystokinin mRNA and peptides in the human brain.

Expression of preprocholecystokinin mRNA was studied in regions of post mortem human brain using RNA blot analysis (Northern blot) and in situ hybridization. Northern blot analysis using a cDNA probe showed high levels of an approximately 0.8 kb preprocholecystokinin mRNA in all regions of neocortex examined. Lower levels of preprocholecystokinin mRNA were detected in amygdaloid body and thalamus. In situ hybridization analysis using the same cDNA probe revealed numerous weakly labelled neurons in different areas of human neocortex and less numerous neurons in hippocampus and amygdaloid body. High-performance liquid-chromatography and gel-chromatography combined with radioimmunoassay of cholecystokinin-like immunoreactivity from human cerebral cortex and caudate nucleus revealed two major forms, one coeluting with sulphated cholecystokinin-8 and the other coeluting with sulphated cholecystokinin-58. Two minor components coeluting with cholecystokinin-4 and cholecystokinin-5 were also detected. The finding of cholecystokinin-like immunoreactivity corresponding to cholecystokinin-8 and cholecystokinin-58 in caudate nucleus where no preprocholecystokinin mRNA was found, indicates the presence of these peptides in afferent nerve terminals.

Blotting, Northern↗
PubMed1991

Repeated electroconvulsive shock increases tachykinin and cholecystokinin mRNA expression in ventral periaqueductal gray.

The effect of repeated electroconvulsive shock (five shocks during 10 days) on preprocholecystokinin and preprotachykinin-A messenger RNA expression was studied in the mesencephalic periaqueductal gray and adjacent areas of rat using in situ hybridization histochemistry with specific oligonucleotide probes. An increased number of preprocholecystokinin and preprotachykinin-A messenger RNA hybridization positive neurons (+30% and +47%, respectively) in the Edinger-Westphal nucleus was observed following repeated electroconvulsive shock. In addition, both preprocholecystokinin and preprotachykinin-A messenger RNA expression, measured as grain density over single neurons, was significantly increased (+37% and +45%, respectively). The results indicate that cholecystokinin- and substance P-containing neurons in the Edinger-Westphal nucleus are activated by repeated electroconvulsive shock, which may be related to the antidepressant and analgesic effects of electroconvulsive shock treatment.

Animals↗
PubMed1991

The effect of selective serotonergic neurotoxin treatment on tachykinin levels in the rat ventral spinal cord.

The levels of 5-hydroxytryptamine and tachykinin neuropeptides substance P, neurokinin A, neurokinin B and neuropeptide K were measured in the spinal cord of rats treated by intraventricular injection of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine. The spinal cord levels of 5-hydroxytryptamine as measured by high performance liquid chromatography with electrochemical detection decreased by more than 90% in the ventral and dorsal cord compared to controls. The levels of substance P as measured by radioimmunoassay were significantly reduced (66%, P less than 0.01) in the ventral lumbar cord only. In this region, neurokinin A, neurokinin B and neuropeptide K levels were determined by combined high performance liquid chromatography and radioimmunoassay. The neurotoxin treatment also caused a significant reduction of neurokinin A (72% reduction, P less than 0.01) and a non-significant reduction of neuropeptide K, but virtually no change in the neurokinin B level. Immunohistochemical studies of the ventral lumbar cord of sham-operated animals showed immunoreactivity for 5-hydroxytryptamine as well as for substance P and neurokinin A in nerve fibres around motor neurons. In neurotoxin-treated rats this region was devoid of immunohistochemically detectable substance P- and neurokinin A-positive fibres and showed very sparse or no 5-hydroxytryptamine immunoreactivity. We conclude that among the tachykinins both neurokinin A and substance P, but probably not neurokinin B, co-exist with 5-hydroxytryptamine in nerve terminals in the rat ventral spinal cord.

5,7-Dihydroxytryptamine↗
PubMed1990

In vivo release of serotonin in cat dorsal vagal complex and cervical ventral horn induced by electrical stimulation of the medullary raphe nuclei.

Extracellular levels of serotonin (5-hydroxytryptamine; 5-HT) were monitored by microdialysis in the dorsal vagal complex (DVC) and the ventral horn of the spinal cord at the level of the phrenic motor nucleus in decerebrated cats. A selective serotonin uptake inhibitor, alaproclate (10(-4) M) was included in the dialysis probe perfusion fluid to increase basal and stimulated levels of 5-HT. Electrical stimulation (30 Hz, 10 V, 0.5 ms) in the nucleus raphe obscurus, containing neurons projecting to the DVC and to the ventral horn, induced a 2-3-fold increase of the 5-HT release in both these regions. After termination of the stimulation, the release gradually decreased during the following 60 min. Substance P, which coexists with 5-HT in descending neurons, did not significantly affect the 5-HT release when it was added (100 microM) to the probe perfusion fluid. The present findings are in accordance with the hypothesis that prolonged release of 5-HT is responsible for the previously demonstrated long-lasting facilitation of phrenic activity following raphe obscurus stimulation.

Animals↗
PubMed1990

N-terminally extended substance P is released together with substance P from rat spinal cord.

The release of different forms of substance P-like immunoreactivity (SP-LI) from superfused slices of rat spinal cord was studied. The released SP-LI was characterized by reverse-phase high-performance liquid chromatography and radioimmunoassay with two antisera directed to the C- and N-terminal parts of SP, respectively. The SP-LI detected in the superfusates with the C-terminally directed antiserum was found to consist of (undeca) SP, SP-sulfoxide and a late eluting component which was not detectable with the N-terminally directed antiserum. This component was also found in neutral extracts of the spinal cord. Upon trypsin digestion, it produced SP-LI detectable with both C- and N-terminally directed antiserum which also coeluted with SP. From these results we conclude that this form of SP-LI most likely corresponds to an N-terminally extended form of SP. An increase of the potassium concentration in the superfusion fluid from 5 to 50 mM evoked an increased overflow of both SP and the N-terminally extended SP. The present results indicate that N-terminally extended SP is released by a calcium-dependent mechanism together with SP from terminals in the spinal cord in response to potassium stimulation.

Animals↗
PubMed1990

Neuropeptides in brain: effects of microwave irradiation and decapitation.

Substance P (SP)-, neurokinin A (NKA)-, neurotensin (NT)-, neuropeptide Y (NPY)- and vasoactive intestinal polypeptide (VIP)-like immunoreactivity (Ll) were measured and characterized by specific radioimmunoassays (RIA) and reverse phase high performance liquid chromatography (HPLC) in extracts of rat brain. Concentrations of SP-Ll, NKA-Ll and NT-Ll in brains of decapitated animals were 59, 49 and 64 percent lower compared to those found in animals sacrificed by focused microwave irradiation (MW). In contrast, no difference in brain NPY-Ll and VIP-Ll levels was found between animals killed by MW and decapitation. HPLC chromatograms of SP-, NKA-, NT- and NPY-Ll showed the same immunoreactive components in extracts of brains from both groups of animals. Thus, no additional immunoreactive components were formed by MW compared to those found after decapitation. The present findings may reflect an MW-induced inhibition of peptidase activity or, perhaps, a more efficient extraction of certain neuropeptides following MW treatment. The results imply that the traditional methods of sacrifice may result in the measurement of spuriously low tissue concentrations of some peptides, e.g. tachykinins, in brain.

Animals↗
PubMed1990

Neuropeptide K is present in human cerebrospinal fluid.

Neurokinin A-like immunoreactivity (NKA-LI) in human cerebrospinal fluid (CSF) was determined by radioimmuno assay (RIA) combined with high performance liquid chromatography (HPLC). The major immunoreactive component did not coelute with NKA, but coeluted with neuropeptide K (NPK), which contains the NKA sequence in its C-terminus. Trypsin treatment of this component from human CSF and of synthetic NPK, produced a substance which coeluted with NKA in the HPLC system. When the NKA-LI was oxidized with hydrogen peroxide and rechromatographed, the immunoreactivity coeluted with NPK sulfoxide. The results indicate that the main part of the NKA-LI in CSF is identical with NPK. The mean concentration of NPK measured in CSF from 6 healthy subjects by HPLC-RIA was 23 +/- 11 (SD) pmol/L.

Chromatography, High Pressure Liquid↗