Distribution of calcitonin gene-related peptide in the central nervous system of the rat by immunocytochemistry and in situ hybridization histochemistry.
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Animals↗
Biomedical subjects
G Skofitsch
Publications and source records attributed to G Skofitsch.
Immunohistochemical localization of calcitonin gene-related peptide in the rat eye. Response to capsaicin pretreatment.
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Animals↗
Pharmacological effects of capsaicin treatment on innervation of the rat kidney with calcitonin gene-related peptide.
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Animals↗
Calcitonin gene-related peptide in the amygdaloid complex of the rat: immunohistochemical and quantitative distribution, and drug effects on calcium dependent, potassium-evoked in vitro release.
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.
Amygdala↗
Substance P afferents regulate ACTH-corticosterone release.
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Adrenocorticotropic Hormone↗
Region-specific noradrenaline depletion by neonatal DSP-4: functional consequences and effect on a coexisting neurotransmitter.
Noradrenaline (NA) depletion following neonatal treatment of rats with DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzyl-amine) was not accompanied by any changes in neuropeptide tyrosine (NPY) levels. After 85-95% NA depletion in the spinal cord of DSP-4-treated rats, the reaction time in the tail withdrawal test was shorter than in the controls but the endogenous activation of the sympathetic nervous system in the baroreceptor reflex remained unchanged. These results suggest that the NA neurons in the spinal cord have an inhibitory function the processing of incoming sensory information.
Animals↗
Calcitonin gene-related peptide in the rat kidney: occurrence, sensitivity to capsaicin, and stimulation of adenylate cyclase.
The occurrence, effects and sensitivity to capsaicin and stimulation of adenylate cyclase of calcitonin gene-related peptide (CGRP) in the rat kidney have been investigated. CGRP-like immunoreactivity was higher in the medulla than in the papilla and the cortex. Capsaicin pretreatment significantly reduced CGRP-like immunoreactivity in the medulla and papilla while a small reduction was found in the cortex. CGRP-immunoreactive nerve fibres were observed surrounding blood vessels and occasionally in the vicinity of renal tubules and between the collecting ducts in the papilla. Some CGRP-immunoreactive fibres were also seen in kidneys from capsaicin-pretreated rats. Infusion of capsaicin (1 microM) through the renal artery of isolated and perfused rat kidney increased the CGRP-like immunoreactivity outflow from the venous effluent. This effect exhibited desensitization at the second challenge with the drug. Infusion of either capsaicin (1 microM) or CGRP (1 microM) reduced the increase of perfusion pressure induced by norepinephrine in isolated perfused rat kidney. Plasma protein extravasation was studied in the various regions of the rat kidney following infusion of capsaicin. No significant change was observed in the medulla, papilla or cortex after capsaicin administration. Adenylate cyclase activity was studied in membrane preparations from cortex, medulla and papilla of rat kidney. Cortical and medullary adenylate cyclase was stimulated in a concentration-dependent manner by salmon calcitonin, rat calcitonin and rat CGRP. Salmon calcitonin in these two areas showed half-maximal effective concentration approximately 1000 times lower and maximal stimulation only slightly higher than those of rat calcitonin and rat CGRP. However, in the papilla, only rat CGRP was able to induce a 60% increase of enzyme activity (half-maximal effective concentration, 19 +/- 1.6 nM). It is concluded that CGRP contained in capsaicin-sensitive sensory nerve may exert a local function in discrete areas of the rat kidney.
Adenylyl Cyclases↗
Galanin and vasopressin coexist in the rat hypothalamo-neurohypophyseal system.
Using indirect immunofluorescence methods and antisera raised against galanin (GAL) and vasopressin (VP), we have demonstrated both peptides coexisting in the very same cell bodies in the supraoptic and magnocellular paraventricular nuclei and the magnocellular accessory cells of the lateral hypothalamic area. Furthermore, dehydration and salt loading, which is known to cause release and depletion of VP and oxytocin from the neurohypophysis, also caused a marked reduction of GAL-like immunoreactivity in the posterior lobe of the pituitary but had no effect on hypothalamic GAL immunoreactivity. Systemically administered GAL caused a brief small increase in blood pressure with no effect on heart rate. A thousandfold molar concentration of GAL, compared of VP, was required to induce comparable effects on blood pressure. GAL itself had no modulatory effect on VP-induced pressor response. Systemically administered GAL resulted in mild diuresis whereas VP caused complete and sustained inhibition of diuresis. GAL had no effect on VP-induced anti-diuresis effects. The significance of the coexistence and corelease of GAL and VP remains to be elucidated.
Animals↗
Species-related differences in the capsaicin-sensitive innervation of the rat and guinea-pig ureter.
1. Comparison of the tissue content of calcitonin gene-related peptide (CGRP)-immunoreactivity (IR) and tachykinin (TK)-IR in the rat and guinea-pig ureter showed that in the rat tissue levels of CGRP-IR were 33-fold higher than those of TK-IR. In the guinea-pig ureter, both peptides were present in nearly the same concentration. 2. The in-vitro release of neuropeptides from guinea-pig and rat ureters was investigated using capsaicin as a stimulus for afferent neurons. Capsaicin induced the simultaneous release of CGRP-IR and TK-IR from the guinea-pig ureter while in the rat only the release of CGRP-IR was detectable. 3. It is known that TK potently stimulate and CGRP inhibits ureteric smooth muscle contractions. When the effect of capsaicin on ureteric motility was investigated in guinea-pig and rat, only in the guinea-pig ureter a stimulatory action ascribable to capsaicin-induced TK release was observed thus supplementing the results obtained by radioimmunoassay. 4. The results show that considerable species differences exist concerning the ratio of CGRP and TK which is stored and released from ureteric afferent nerve terminals. As a consequence, different functional responses are obtained in both species upon stimulation of these neurons by capsaicin. In the rat ureter, the capsaicin-sensitive innervation seems to be only inhibitory while in the guinea-pig stimulatory and inhibitory transmitters are released. The physiological significance of the simultaneous release of transmitters with opposing effects needs further investigation.
Animals↗
Atrial natriuretic peptide in the central nervous system of the rat.
1. Studies of the presence of atrial natriuretic peptide immunoreactivity and receptor binding sites in the central nervous system have revealed unusual sites of interest. 2. As a result, numerous studies have appeared that indicate that brain atrial natriuretic peptide is implicated in the regulation of blood pressure, fluid and sodium balance, cerebral blood flow, brain microcirculation, blood-brain barrier function, and cerebrospinal fluid production. 3. Alteration of the atrial natriuretic peptide system in the brain could have important implications in hypertensive disease and disorders of water balance in the central nervous system.
Animals↗
Abolition of vagino-cervical stimulation-induced analgesia by capsaicin administered to neonatal, but not adult rats.
We have previously reported that vagino-cervical mechanical stimulation (VS or probing) produces analgesia in rats. Neonatal treatment with capsaicin (CAP) has been shown to reduce the concentrations of several neuropeptides in dorsal root ganglia, spinal cord, and autonomic ganglia, via a neurotoxic effect. In the present study, we report that CAP administered in the neonatal period abolishes the analgesic effect of probing in adulthood. In addition, we report that the ability of VS to potentiate the lordosis response to manual stimulation of the flanks is abolished by neonatal CAP treatment. By contrast, rats treated as adults with CAP show the typical VS-produced effects of analgesia and potentiation of the lordosis response. Our results suggest that neonatal, but not adult, CAP treatment depletes a neuropeptide(s) that mediates the analgesia and lordosis-inducing effects of VS.
Age Factors↗
Distribution of immunoreactive melanin-concentrating hormone in the central nervous system of the rat.
The distribution of melanin-concentrating hormone-like immunoreactivity (MCH-LI) in 41 microdissected brain and spinal cord regions was determined using radioimmunoassay with antibodies to salmon MCH. The highest concentration of MCH-LI was detected just ventral to the zona incerta (subzona incerta) (2923.2 fmol/mg protein). Very high concentrations of MCH-LI (greater than 1000 fmol/mg protein) were detected also in the nucleus of the diagonal band, medial forebrain bundle, posterior hypothalamic nucleus and medial mammillary nucleus. High concentrations of the peptide (between 500-1000 fmol/mg protein) were measured in 11 brain regions, including bed nucleus of stria terminalis, paraventricular nucleus, anterior hypothalamic nucleus, median eminence, parabrachial nucleus. Moderate concentrations of MCH-LI (between 250-500 fmol/mg protein) were measured in 16 brain regions, such as frontal cortex, central amygdaloid nucleus, medial septum, periventricular nucleus (preoptic) and nucleus of the solitary tract. Low concentrations of MCH-LI (less than 250 fmol/mg protein) were measured in 9 brain regions such as cortical areas, hippocampus, caudate nucleus and substantia nigra. Cervical spinal cord and neurointermediate lobe of the pituitary gland contain low concentrations of the peptide.
Animals↗
Distribution of immunoreactive atrial natriuretic peptides in the central nervous system of the rat.
The distribution of immunoreactive (ir) atrial natriuretic peptides (ANPs) in 47 microdissected brain and spinal cord regions of the rat was determined by radioimmunoassay. The highest concentrations of ir-ANPs exist in the paraventricular nucleus and median preoptic nucleus (580.9 and 558.0 fmol/mg protein, respectively). High concentrations of ir-ANP (greater than 300 fmol/mg protein) are present in the interpeduncular nucleus, preoptic and hypothalamic periventricular nuclei, median eminence and organum vasculosum of the lamina terminalis. Moderate concentrations of ir-ANPs (between 100 and 300 fmol/mg protein) are found in 16 brain regions such as the bed nucleus of the stria terminalis, nucleus of the diagonal band, most of the hypothalamic nuclei, central gray, locus coeruleus and parabrachial nuclei. Low levels of ir-ANPs (less than 100 fmol/mg protein) exist in 22 brain regions including cortical areas, amygdala, caudate nucleus, nucleus accumbens, hippocampus, supraoptic nucleus, subfornical organ, medial mammillary nucleus, substantia nigra, dorsal raphe nucleus, cerebellum, nucleus of the solitary tract and others. Cervical spinal cord and neurointermediate lobe of pituitary gland contain low levels of ir-ANPs.
Animals↗
Immunocytochemical localization of atrial natriuretic factor, galanin and calcitonin gene-related peptide within the rat interpeduncular nucleus.
The immunocytochemical localization of atrial natriuretic factor (ANF), galanin (GAL), and calcitonin gene-related peptide (CGRP) in specific subnuclei of the interpeduncular nucleus (IPN) was determined by immunocytochemistry in rats with and without intraventricular colchicine injection. ANF-positive processes were present within the ovoid regions of the rostral subnucleus, the dorsal lateral subnuclei, and were densely concentrated along the medial aspects of the lateral subnuclei in the caudal half of the IPN. GAL-positive processes were concentrated within the lateral subnuclei, in a narrow band extending over the central and intermediate subnuclei, and within the central subnuclei. GAL-positive cell bodies were present in a narrow band ventral to the rostral subnucleus, and in the ventrolateral corners of the caudal IPN. CGRP-positive processes were primarily localized within the dorsal lateral subnuclei and dorsal aspects of the lateral subnuclei. The presence of ANF, GAL and CGRP peptides within the IPN in patterns similar to previously described localizations of substance P, vasoactive intestinal peptide, serotonin and Leu-enkephalin provides a morphologic basis for modulation of complex physiological actions yet to be elucidated.
Animals↗
Melanin-concentrating hormone: unique peptide neuronal system in the rat brain and pituitary gland.
A unique neuronal system was detected in the rat central nervous system by immunohistochemistry and radioimmunoassay with antibodies to salmon melanin-concentrating hormone (MCH). MCH-like immunoreactive (MCH-LI) cell bodies were confined to the hypothalamus. MCH-LI fibers were found throughout the brain but were most prevalent in hypothalamus, mesencephalon, and pons-medulla regions. High concentrations of MCH-LI were measured in the hypothalamic medial forebrain bundle (MFB), posterior hypothalamic nucleus, and nucleus of the diagonal band. Reversed-phase high-performance liquid chromatography of MFB extracts from rat brain indicate that MCH-like peptide from the rat has a different retention time than that of the salmon MCH. An osmotic stimulus (2% NaCl as drinking water for 120 hr) caused a marked increase in MCH-LI concentrations in the lateral hypothalamus and neurointermediate lobe. The present studies establish the presence of MCH-like peptide in the rat brain. The MCH-LI neuronal system is well situated to coordinate complex functions such as regulation of water intake.
Animals↗
Cardiovascular effects of calcitonin gene-related peptide in the pithed rat: comparison with substance P.
Recently it has been shown that calcitonin gene-related peptide (CGRP) and substance P (SP) are coexisting in central and peripheral nerve endings of sensory neurons. In the present study we compared the vasodepressor and plasma extravasating activity of CGRP with that of SP. Systemic administration of CGRP to pithed, vagotomized rats evoked a dose dependent, long lasting vasodilation accompanied by a parallel rise in heart rate. The tachycardic response to CGRP may indicate a direct positive chronotropic action on the heart since this effect could not be blocked by beta-adrenoceptor blockade. For any equimolar dose the hypotensive effect of CGRP was much larger than that of SP. Both, CGRP and SP, showed a more pronounced decrease in mean arterial blood pressure after elevation of basal blood pressure levels by constant infusion of either phenylephrine, arginine-vasopressin, or angiotensin II. After systemic administration in equimolar doses CGRP was much less effective in producing plasma extravasation than SP. In conclusion, at equimolar doses CGRP is 10 times more potent than SP in producing vasodilatation but it possesses less than a third of the potency of equimolar doses of SP in producing plasma extravasation.
Angiotensin II↗
Effect of chronic reserpine and desmethylimipramine treatment on CRF-like immunoreactivity of discrete brain areas of rat.
The corticotropin releasing factor-like immunoreactivity (CRF-LI) of discrete areas of rat brain were measured following reserpine (2 mg/kg i.p. for 3 days) or chronic desmethylimipramine (DMI) (20 mg/kg i.p. for 14 days) treatment. Reserpine caused a 40% and 36% reduction in the (CRF-LI) of the median eminence (ME) and posterior pituitary respectively, while DMI caused a 61% rise in CRF-LI of the posterior pituitary only. The results support the role of monoaminergic regulation of CRF release from the ME and further suggest an interaction between monoaminergic and CRF neurons in the posterior pituitary.
Animals↗
Suggestive evidence for a functional unit between mast cells and substance P fibers in the rat diaphragm and mesentery.
A close spatial relationship between serotonin-containing mast cells and substance P-containing nerves was shown by immunohistochemistry using a combination of antisera specific for serotonin and substance P. This supports earlier morphological results suggesting an innervation of mast cells and pharmacological studies which postulate an influence of substance P on the release of histamine from mast cells.
Animals↗