Capsaicin and potassium evoked substance P release from the nucleus tractus solitarius and spinal trigeminal nucleus in vitro.
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Animals↗
Biomedical subjects
D M Jacobowitz
Publications and source records attributed to D M Jacobowitz.
Effect of capsaicin administration to neonatal rats on the substance P content of discrete CNS regions.
Substance P (SP) levels were determined by radioimmunoassay in microdissected CNS regions of adult animals treated with capsaicin as neonates and of vehicle controls. Capsaicin treatment reduced the SP content of the spinal trigeminal nucleus and the dorsal horn of the spinal cord whereas it had no effect on the SP levels in the ventral horn of the spinal cord, the nucleus tractus solitarius or in midbrain and forebrain areas analyzed.
Animals↗
Lithium increases serotonin release and decreases serotonin receptors in the hippocampus.
The effects of long-term lithium administration on pre- and postsynaptic processes involved in serotonergic neurotransmission were measured in rat hippocampus and cerebral cortex. Long-term lithium administration increased both basal and potassium chloride-stimulated release of endogenous serotonin from the hippocampus but not from the cortex. Serotonergic receptor binding was reduced in the hippocampus but not in the cortex. These results suggest a mechanism by which lithium may stabilize serotonin neurotransmission.
Animals↗
Muscarinic receptor binding following cholinergic nerve lesions of the cingulate cortex and hippocampus of the rat.
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Afferent Pathways↗
Central cardiovascular effects of prostacyclin.
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Animals↗
Gastric and pyloric motor response to sympathetic nerve stimulation after chemical sympathectomy.
This study evaluated the effect of electrical stimulation of the greater splanchnic nerve on gastric and gastroduodenal motility in 6-hydroxydopamine (6-OHDA)-pretreated anesthetized dogs. Biopsies from the stomach, pylorus and duodenum were obtained and analyzed by catecholamine fluorescence microscopy. Degeneration of adrenergic terminals in Auerbach's plexus was complete at 1 week. The majority of stimulations in control dogs or dogs treated with 6--OHDA produced contractions in the gastric body, antrum, and pylorus and relaxation of inhibition in the duodenum. The excitatory motor responses in the gastric body, antrum and pylorus were unaffected by the administration of hexamethonium. Following atropine administration, contractions due to splanchnic nerve stimulation virtually were abolished in the antrum, pylorus and duodenum and were reduced in number in the gastric body. Relaxation and inhibition were no longer observed in the duodenum after atropine. The greater splanchnic nerve appears to contain both excitatory are inhibitory cholinergic pathways to the musculature of the stomach, pylorus, and duodenum.
Animals↗
Secretin immunoreactivity in rat and pig brain.
Secretin immunoreactivity in rat and pig brain has been identified and characterized utilizing a highly specific radioimmunoassay and fractionation on a high pressure liquid chromatographic system reverse phase column. One immunoreactive peak from each brain extract was observed. Secretin immunoreactivity from rat brain and duodenum coelute, but eluted slightly ahead of the immunoreactivity from pig brain and duodenum and from synthetic porcine secretin. Immunoreactive secretin is widely distributed in the thalamus, hypothalamus and olfactory bulb, cerebral cortex, midbrain, septum, striatum, hippocampus, medulla and pons. The highest concentrations occur in the pineal and the pituitary gland.
Animals↗
Catecholamines and vasopressin in forebrain nuclei of hypertension prone and resistant rats.
Catecholamine and vasopressin content were studied in discrete brain nuclei of the Sabra strain of hypertension prone (SBH) and resistant (SBN) rats. Higher concentrations of dopamine, norepinephrine and epinephrine were observed in the median eminence of SBN compared to SBH or controls (SB) rats. Dopamine and epinephrine levels were higher in the lateral septal nucleus of SBH rats as compared to SBN or SB. Vasopressin content in discrete regions along the hypothalamo-pituitary axis was elevated in both SBH and SBN as compared to SB, but were especially elevated in the SBH group. The catecholamine and vasopressin changes found in SBH are different than those described in other genetically hypertensive rats indicating a difference in either the pathogenesis or central response to hypertension of this strain.
Animals↗
Biochemical localization and characterization of bombesin-like peptides in discrete regions of rat brain.
A radioimmunoassay using an antiserum which recognizes the C-terminal of bombesin was used to determine the regional distribution of bombesin-like peptides in discrete regions of rat brain. The concentration of endogenous bombesin-like peptides was 30-fold greater in high (substantia gelatinosa trigemini, nucleus tractus solitarius, interpeduncular nucleus and arcuate nucleus) than low regions (caudate, hippocampus and cingulate cortex). When brain extracts were fractionated using high pressure liquid chromatography techniques two major peaks of immunoreactivity were obtained, the more hydrophobic peptide coeluted with synthetic bombesin. It is concluded that the current evidence supports the contention that bombesin may be a neuroactive peptide in the brain.
Animals↗
Release of alpha-melanocyte stimulating hormone into rat and human cerebrospinal fluid in vivo and from rat hypothalamus slices in vitro.
The release of alpha-melanocyte stimulating hormone (alpha-MSH) from central nervous system neurons was investigated and demonstrated in vivo and in vitro. alpha-MSH immunoreactivity in rat and human cerebrospinal fluid (CSF) is comprised of deacetylated alpha-MSH, alpha-MSH and the methionine sulfoxide forms of these peptides. The sulfoxides are formed artifactually upon extraction. alpha-MSH in rat CSF is unaffected by hypophysectomy but is markedly increased by electrical stimulation of the mesencephalic central gray. These data indicate that CSF alpha-MSH is primarily of neuronal origin, alpha-MSH is also released in a calcium dependent manner from hypothalamic slices in vitro. The fact that the release of alpha-MSH is stimulated by veratridine and inhibited by tetrodotoxin demonstrates the necessity for neuronal sodium influx for alpha-MSH release. The presence of an alpha-MSH neurosecretory process supports a neurotropic role for this peptide in the central nervous system.
Animals↗
Comparison of biological and behavioral activities of alpha- and gamma-melanocyte stimulating hormones.
The biological and behavioral activities of gamma-MSH (gamma-MSH) and alpha-MSH (alpha-MSH) were compared using three different tests: darkening of the skin of Anolis, grooming behavior of rats, and performance of a visual discrimination task by rats. When incubated with the Anolis skin, both peptides cause skin darkening. However, alpha-MSH is much more potent than gamma-MSH. The alpha-MSH effect is not antagonized by coincubation with gamma-MSH. When given intraventricularly to rats, alpha-MSH induces a marked grooming behavior. This effect was not noted upon administration of gamma-MSH. Injection of gamma-MSH with the alpha-MSH did not produce a grooming response significantly different from alpha-MSH alone. In the visual discrimination task, the two peptides had opposite effects on the rate at which rats learned the initial discrimination and a subsequent reversal. The peptides were injected intraperitoneally prior to behavioral testing. Following alpha-MSH, rats learned the discrimination and subsequent reversal faster than the control rats. Following gamma-MSH, rats learned the initial discrimination at approximately the same rate as controls, and learned the reversal much slower. These results are discussed in terms of the similarity and differences in the mechanisms of action of alpha-MSH and gamma-MSH.
Animals↗
Identification, characterization and distribution of motilin immunoreactivity in the rat central nervous system.
Motilin-immunoreactivity was evaluated in rat brain using 15 different antisera and by combining gel filtration, high pressure gel filtration and reverse phase high pressure liquid chromatography with radioimmunoassay. Gel filtration chromatography demonstrated a high molecular weight and low molecular weight form of immunoreactive motilin. The high molecular weight form predominated in brain while the low molecular weight peptide was the predominant form of duodenum. The low molecular weight immunoreactive motilin was indistinguishable from synthetic porcine motilin by gel filtration and high molecular weight gel filtration. Low molecular weight rat motilin could, however, be distinguished from synthetic porcine motilin by high pressure liquid chromatography and certain antisera. Immunological results suggest that the slight structural difference may be in the N-terminal portion of the molecule. Immunoreactivity was measured in grossly and microdissected regions of the rat brain. The peptide had quite a unique distribution as highest concentrations are observed in the cerebellum. High concentrations were also observed in hypothalamic nuclei. Particularly high concentrations were noted in the organum vasculosum lamina terminalis. Lowest motilin concentrations in the rat brain were in the pons and the medulla. The distribution of motilin in rat brain suggests that it may have roles in regulating both neuroendocrine and neurological processes.
Animals↗
Mapping of motilin-immunoreactive neurons of the rat brain.
Motilin immunofluorescence was observed in the rat brain by means of N- and C-terminally directed antisera. A detailed mapping of the localization of motilin-like immunoreactive neurons in the rat forebrain is presented. Colchicine pretreatment revealed many cell bodies in the mediobasal hypothalamus. A small number of cells were observed in the organum vasculosum lamina terminalis (OVLT) region. A rich innervation of varicose fibers was observed in the median eminence and OVLT. Fibers of varying densities were observed in the preoptic area, nucleus interstitialis stria terminalis, hypothalamic nuclei, basal hypothalamus, amygdala, mammillary doby and central gray. The localization of these neurons suggests that motilin, like other brain peptides serves a variety of functions including neuroendocrine regulation.
Amygdala↗
The distribution of bovine pancreatic polypeptide-like immunoreactive neurons in rat brain.
Using the indirect immunofluorescent technique, bovine pancreatic polypeptide (BPP)-like immunoreactive nerve fibers and cell bodies were observed widely distributed in rat brain. A detailed stereotaxic atlas of BPP-immunoreactive neurons was prepared. Large numbers of BPP-containing perikarya were observed in the acute nucleus, with scattered cells in the cerebral cortex, nucleus olfactorius anterior, nucleus tractus diagonalis, olfactory tubercle, nucleus accumbens, neostriatum, nucleus interstitialis stria terminalis, nucleus preopticus medialis, area retrochiasmatica, zona interna of the median eminence, substantia grisea centralis, locus coeruleus, nucleus tractus solitarius, and in the region of the nucleus reticularis lateralis. Large numbers of varicose BPP-like nerve fibers were observed in the following nuclei: accumbens, interstitialis stria terminalis, preopticus medialis, preopticus suprachiasmaticus, suprachiasmaticus, periventricular thalamic and hypothalamic, paraventricularis, dorsomedialis, ventromedialis, arcuatus, parabrachialis dorsalis, tractus solitarius and the substantia gelatinosa trigemini. The present findings suggest that a BPP-like peptide may be involved in significant neuronal circuitry, possibly in a neurotransmitter or neuromodulator role. However, the exact identity of this peptide and its physiological role remain to be determined.
Animals↗
Evidence that N-acetylation regulates the behavioral activity of alpha-MSH in the rat and human central nervous system.
alpha-MSH immunoreactive peptides were fractionated and characterized in rat and human brain and rat pituitary by reversed phase high pressure liquid chromatographic techniques. alpha-MSH and deacetylated alpha-MSH were two major naturally existing peptides in both brain and pituitary gland. Subsequent experiments examined the roles of these two peptides in neuronal function. The alpha-MSH was clearly more effective than deacetylated alpha-MSH in improving performance on a visual discrimination task after intraperitoneal administration and in inducing excessive grooming after intraventricular administration. The difference in behavioral potency may be explained by the fact that alpha-MSH was much more resistant to peptidase degradation than was deacetylated alpha-MSH. N-acetylation of alpha-MSH may be an effective regulatory process for modulating the behavioral potency of the secretory product of alpha-MSH-containing pituitary cells and neurons.
Acetylation↗
Cardiovascular and sympathetic responses to PGF2 alpha injection into hypothalamic nuclei.
Injection of prostaglandin F2 alpha (1 nmol/rat) into the paraventricular, dorsomedial and posterior hypothalamic nuclei of halothane anesthetized rats elicited rapid increases of heart rate and blood pressure. The injection of this same dose of prostaglandin F2 alpha into the cerebroventricular system or intravenously had no effect on these parameters. The cardiovascular responses observed following prostaglandin F2 alpha injection into these hypothalamic nuclei were accompanied by increases in plasma levels of norepinephrine and epinephrine, with peak levels at the maximal cardiovascular response. This study suggests a possible role for prostaglandin F2 alpha in modulation of the cardiovascular system via specific hypothalamic nuclei.
Animals↗
Identification, characterization, and distribution of secretin immunoreactivity in rat and pig brain.
Secretin immunoreactivity was detected in the central nervous system of the rat and pig with a highly specific radioimmunoassay. The secretin immunoreactivity in the rat and pig brain and duodenum extracts was fractionated by using a reverse-phase high-pressure liquid chromatographic system. The immunoreactive secretin from pig brain and duodenum coeluted precisely with synthetic porcine secretin. However, immunoreactive secretin extracted from rat brain and duodenum eluted slightly before porcine secretin. These data suggest a slight difference in the structure of rat and pig secretin. The detection of secretin in the brain lays the groundwork for studies to determine the role of the peptide in central nervous system function.
Animals↗
Evidence that noradrenaline modulates the increase in striatal dopamine metabolism induced by muscarinic receptor stimulation.
The effect of oxotremorine was studied on the concentration of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylethylglycol (MHPG) in the corpus striatum of rats. At a dose of 1 mg/kg oxotremorine increased HVA levels by 68% and MHPG, by 51%. MHPG was also increased in the nucl. accumbens (58%) and neocortex (42%). Pretreatment with clonidine, 0.1 mg/kg abolished the increase in MHPG in the striatum and significantly inhibited the rise in HVA. 1-Propranolol 2.5 mg/kg, but not d-propranolol, had an effect similar to that of clonidine. A lower dose of oxotremorine (0.5 mg/kg) increased striatal HVA by 36% but did not alter MHPG levels. This increase in HVA was not reduced by 1-propranolol. Eight days after bilateral lesions of the locus coeruleus, there was a reduction in the basal concentrations of noradrenaline (41%) and MHPG (57%) in the striatum. The data suggest that at higher doses of oxotremorine (1 mg/kg), but not a lower dose (0.5 mg/kg), a noradrenergic pathway is stimulated to increase the rate of metabolism of noradrenaline in the striatum. Oxotremorine also appears to increase dopamine metabolism in the striatum by at least two separate mechanisms, one of which involves the mediation of noradrenaline.
Animals↗