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M Palkovits

Publications and source records attributed to M Palkovits.

481 records · Page 27Linked to original sources

Distribution of norepinephrine and dopamine in cerebral cortical areas of the rat.

Concentrations of norepinephrine and dopamine were determined using enzyme isotope assay in 27 microdissected cerebral cortical areas of the rat. A detailed map is presented for microdissection of rat cerebral cortex. Norepinephrine was found in low but still measurable quantities throughout the cortex. Differences between cortical areas are also low. Relatively highest levels were demonstrated in the pyriform, insular and entorhinal cortices. The distribution of dopamine was found to be uneven with a maximal regional difference of 1:24. Concentration of dopamine was in all areas lower than that of norepinephrine. The highest dopamine concentration (2,4 ng/mg protein) was measured in the rostral pyriform cortex but other mesocortical (cingulate, frontal, insular and entorhinal) dopaminergic areas also contained relatively high amounts. Except for the caudal occipital and caudal entorhinal cortices all regions studied contained measurable quantities of dopamine. Its low concentration relative to norepinephrine (below 15%) suggests that in the cortical areas studied dopamine is present as the precursor of norepinephrine.

Animals↗

Light and electron microscopic studies on the medial forebrain bundle in rat: III. Degenerated nerve elements in the medial hypothalamic nuclei following surgical transections of the medial forebrain bundle.

Transections of the rat medial forebrain bundle at various levels and the separation of the medial and lateral hypothalamus were performed to study with light and electron microscopy axonal and terminal degeneration in the arcuate, ventromedial and dorsomedial nuclei and in the median eminence. Fibres entering the MFB from various directions participate in the innervation of the arcuate nucleus. The bulk of extrahypothalamic fibres terminating in the median eminence derive from the lower brain stem and reach their target through the MFB. Preoptic originating and transient fibres also terminate in the median eminence. Following parasagittal separation of the medial and lateral hypothalamus massive degeneration was found in both layers of the median eminence. This is likely to be due to interruption of the supraoptic-hypophyseal tract but axons of intrinsic MFB-neurons might also contribute to the innervation of the median eminence.

Animals↗

Adrenergic projections from the lower brainstem to the hypothalamic paraventricular nucleus, the lateral hypothalamic area and the central nucleus of the amygdala in rats.

Fine networks of phenylethanolamine N-methyltransferase (PNMT)-immunoreactive fibers are found in the hypothalamic paraventricular nucleus--mainly in the anterior, dorsal and dorso-medial parvicellular subdivisions, the lateral hypothalamus (dorsal, lateral and ventral to the fornix) and in the central amygdaloid nucleus. Coronal hemisections of the brainstem through the rostral level of the medulla oblongata show that most hypothalamic and amygdaloid PNMT fibers arise from the medullary adrenergic cell groups. Fourteen, but not 10 days after total hemisections, PNMT fibers disappeared almost completely from the hypothalamus and amygdala, ipsilateral to the knife cuts. A small decrease was also observed in the ventral, lateral hypothalamus on the contralateral side. Partial depletion of PNMT-immunoreactivity in the hypothalamus and the amygdala after medial or lateral brainstem hemisections indicates that ascending PNMT-immunoreactive fibers pass through mainly the lateral portion of the medulla, but some fibers also in its medial portion. Midsagittal transection of the diencephalon slightly reduced PNMT immunostaining in the paraventricular nucleus and the lateral hypothalamus bilaterally. The results show that the ascending PNMT system essentially is ipsilateral, but probably with a small crossing-over component, both at the diencephalic and lower brainstem level.

Adrenergic Fibers↗

Vesicular monoamine transporters in the rat stomach.

Cellular distribution of vesicular monoamine transporters (VMATs), known to regulate vesicular storage and release of biogenic amines (i.e., catecholamines, serotonin, histamine, etc.), have been studied in the rat stomach using in situ hybridization histochemistry (ISHH) and immunohistochemical (IHC) techniques. 35S-UTP labeled riboprobes showed that mRNAs of both VMATs are expressed in the gastric mucosa. A combination of ISHH and IHC verified that most of the parietal cells (among other epithelial cells) express mRNA of the peripheral type transporter (VMAT1) while enterochromaffin-like cells (ECL) of the fundic mucosa express mRNA of the central type (VMAT2). In addition, with double fluorescent IHC we detected VMAT1 protein in serotoninergic enterochromaffin cells (EC) of the stomach and in gastrin producing G cells of the antral mucosa. Similarly to the fundus, VMAT2 protein was present in ECL cells and in the enteric plexus. Surprisingly, serotonin- and/or histamine-containing cells in the connective tissue compartments of the stomach (i.e., lamina propria and submucosa), immunoreactive for a mast cell specific antigen, displayed neither VMATI nor VMAT2 immunoreactivity. Distribution of VMATs in the rat stomach support our previous observations on aminergic properties of two important gastrointestinal (GI) epithelial cell populations primarily known for other specific secretory products, i.e. dopaminergic properties of acid producing parietal cells and histaminergic properties of gastrin producing G cells. These data emphasize the existence of a non-neuronal, intrinsic aminergic system in the GI tract.

Animals↗

Susceptibility of dopamine D5 receptor targeted mice to cysteamine.

BACKGROUND: Recently we demonstrated that gastric mucosa of rats can synthesize, store and release dopamine. Out of five different subtypes, mRNA of D5 (=D1b) dopamine receptor is very abundant in the gastric epithelium. D1 receptor selective dopamine agonists have been shown to protect against experimental gastro-duodenal lesions. AIMS: To test the hypothesis that protective effects of dopamine involve D5 receptors, mucosal lesions were induced in D5 receptor deficient (KO) and wild-type (WT) mice using cysteamine. Morphology and gastric acid secretion of D5 KO mice were also studied. METHODS: Single doses of 600 mg/kg, 300 mg/kg cysteamine or vehicle were administered subcutaneously to fasted animals. After 24 h, number and severity of gastro-duodenal lesions were analyzed. Basal and histamine-induced maximal gastric acid output were measured by a stomach-sac wash-through method. RESULTS: All the KOs in the 600 mg/kg cysteamine group died within 4 h showing symptoms of toxicity while three out of four WTs survived (P<0.05). Mortality after 300 mg/kg cysteamine was significantly higher in KOs versus the WTs: 6/14 versus 2/11, P<0.05. Gastric lesion-index was also significantly higher in KOs (median, middle quartile): four (3-9) versus 0 (0-0), P<0.05. Duodenal lesions did not develop from this single dose of cysteamine in either genotype. Basal and histamine-induced maximal gastric acid output were comparable in the two genotypes. CONCLUSIONS: This study demonstrates that loss of D5 receptor causes mucosal vulnerability and increased toxicity of cysteamine in genetically manipulated mice. Thus, D5 receptor subtype is indeed likely to be involved in protective effects of dopamine in the stomach.

Animals↗

Neonatal monosodium glutamate treatment abolishes both delta opioid receptor-induced and alpha-2 adrenoceptor-mediated gastroprotection in the lower brainstem in rats.

Neonatal monosodium glutamate treatment reduced immunoreactive beta-endorphin content in the mediobasal hypothalamus by 50% in adult, male Wistar rats as compared to hypertonic saline-treated littermates; there was also a moderate (approx. 25%) reduction in the rostral part of the nucleus of the solitary tract. In sham-treated adults the intracisternally injected alpha-2 adenoceptor stimulant clonidine (0.47 nmol/rat) and the delta opioid receptor type agonist (D-Ala(2), D-Leu(5))-enkephalin (0.8 nmol/rat) reduced acidified ethanol-induced mucosal lesions in the stomach by 84.1 and 77.5%, respectively, whereas the same doses were completely ineffective in rats treated neonatally by monosodium glutamate. The data taken together with the results of previous studies with the same substances in rats with retroarcuate knife cuts suggest that neuronal damage in the nucleus of the solitary tract region rather than in the arcuate nucleus is responsible for the changes seen in the pharmacological responsiveness.

Adrenergic alpha-Agonists↗

A dynorphinergic pathway of Leu-enkephalin production in rat substantia nigra.

The amino acid sequence of the opioid peptide Leu-enkephalin is found within several larger peptides, which are generated from the precursors proenkephalin and prodynorphin. Proenkephalin contains four copies of the sequence of Met-enkephalin, a single copy of the sequence of Leu-enkephalin and one copy each of two extended Met-enkephalin sequences. Proenkephalin contains three peptides--alpha-neo-endorphin, dynorphin A and dynorphin B--the N-terminal sequences of which are identical to that of Leu-enkephalin. There is good evidence that the large amounts of Leu-enkephalin found in the adrenal medulla are generated from the precursor proenkephalin, but as yet prodynorphin has not been shown to be processed to yield Leu-enkephalin. We show here that the relatively high levels of Leu-enkephalin found in the rat substantia nigra are supplied by striatonigral axons and generated from the precursor prodynorphin.

Animals↗

Role of catecholamines and vasopressin in cardiovascular responses to bilateral dorsolateral transection of the medulla oblongata in the rat.

The role of sympathetic and other pressor systems in the development of fulminant hypertension induced by baroreceptor deafferentation is still unclear. We studied the effects of acute hypertension produced by bilateral dorsomedullary knife cuts lateral to the nucleus tractus solitarii (DMK-cut) on plasma norepinephrine (NE), epinephrine (E), and vasopressin (VP) in conscious, tail-artery-cannulated rats. In saline-pretreated (SAL) rats, DMK-cut caused a significant (p less than 0.001) rise in mean blood pressure (MAP, +68 +/- 3 mm Hg), heart rate (HR, +97 +/- 19 bpm), NE (+2.5 +/- 0.3 ng/ml), E (+2.7 +/- 0.4 ng/ml), and VP (+115 +/- 34 pg/ml) compared to sham-operated rats. Neither sympathetic blockade with chlorisondamine (CHLO, 10 mg/kg, s.c.) nor elimination of the pressor effects of VP by use of Brattleboro rats or the VP pressor antagonist resulted in a maximal MAP response significantly different from that in the SAL + DMK-cut group. However, CHLO-pretreatment of Brattleboro rats completely abolished the increase in MAP and HR. It is suggested that the bilateral DMK-cut causes acute hypertension, probably due to the abolition of baroreceptor reflexes by central interruption of neural connections of the nucleus tractus solitarii. It appears that both the increased sympathoadrenomedullary activity and VP release normally contribute to this hypertension; however, either one is sufficient to sustain the elevated blood pressure.

Animals↗

Neurotransmitters and neuropeptides in the baroreceptor reflex arc: connections between the nucleus of the solitary tract and the ventrolateral medulla oblongata in the rat.

The primary baroreceptor area (nucleus of the solitary tract-NTS) is anatomically interconnected with the rostral ("vasomotor area") and the caudal ("vasodepressor area") ventrolateral medulla by a well-defined arc of neuronal pathways. The chemical character and the direction of these pathways have been investigated with immunohistochemical and neurochemical techniques in intact and brainstem-operated rats. The transection of the neuronal arc resulted in an accumulation of tyrosine hydroxylase immunoreactivity in a small group of cells in the NTS adjacent to the area postrema, ipsilateral to the knife cut. Decreased angiotensinogen mRNA and atrial natriuretic peptide concentrations were measured in the ventrolateral medulla after the cut, and an accumulation of angiotensin II-immunoreactivity was found in neuronal perikarya in the ipsilateral NTS. Intracranial vagotomy caused marked depletions in glutamate levels in the subcommissural portion of the NTS and in the caudal ventrolateral medulla but nowhere else in the brainstem investigated including the rostral ventrolateral medulla.

Angiotensin II↗

Adenylate cyclase-cyclic AMP-phosphodiesterase system in microdissected brain areas of normotensive and spontaneously hypertensive rats.

The topographical distribution of the adenylate-cyclase-cyclic adenosine monophosphate-phosphodiesterase system was investigated in specific brain areas of rats, and compared with spontaneously hypertensive rats. In normotensive animals, brain cyclic adenosine monophosphate levels were quite uniform (between 7.14 and 13.04 pmol/mg protein) with highest concentrations in catecholamine-containing cell groups. In contrast, the distribution of basal adenylate cyclase and phosphodiesterase activity is not uniform. The unstimulated adenylate cyclase activity was very low in the striatum and catecholamine-containing cell groups in the medulla oblongata (A1C1-cell groups) and very high in the central gray matter and the cerebellum, where the lowest phosphodiesterase activities were measured. In spontaneously hypertensive rats, altered cyclic adenosine monophosphate levels were found in 17 of 36 brain areas investigated in comparison to those of normotensive rats. Increased concentrations were found in regions which are known to participate in the central regulation of blood pressure (nucleus of the solitary tract, A1C1 catecholaminergic cell groups in the ventrolateral medulla oblongata, locus coeruleus) and in the periaqueductal central gray matter, the hippocampus and the cingulate cortex. Lower levels were measured only in hypothalamic nuclei, especially in the paraventricular and dorsomedial nucleus. No significant differences in basal adenylate cyclase activity were found in spontaneously hypertensive rats compared with Wistar-Kyoto control rats, while phosphodiesterase activity was generally higher in spontaneously hypertensive rats, most significantly in the medulla oblongata. Present data show that characterization of the adenylate cyclase-cyclic adenosine monophosphate-phosphodiesterase system helps to localize structural and/or functional differences between the spontaneously hypertensive rat and its normotensive control rat and indicate that more than one functional system is affected in spontaneous hypertension.

3',5'-Cyclic-AMP Phosphodiesterases↗