Changes In Neuropeptide Levels Research Articles

Vagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice.

Postoperative pain is a major clinical problem imposing a significant burden on patients and society. In a survey 2 years after orthopedic surgery, 57% of patients reported persisting postoperative pain. However, only limited progress has been made in the development of safe and effective therapies to prevent the onset and chronification of pain after orthopedic surgery. We established a tibial fracture mouse model that recapitulates clinically relevant orthopedic trauma surgery, which causes changes in neuropeptide levels in dorsal root ganglia and sustained neuroinflammation in the spinal cord. Here, we monitored extended pain behavior in this model, observing chronic bilateral hindpaw mechanical allodynia in both male and female C57BL/6J mice that persisted for >3 months after surgery. We also tested the analgesic effects of a novel, minimally invasive, bioelectronic approach to percutaneously stimulate the vagus nerve (termed percutaneous vagus nerve stimulation [pVNS]). Weekly pVNS treatment for 30 minutes at 10 Hz for 3 weeks after the surgery strongly reduced pain behaviors compared with untreated controls. Percutaneous vagus nerve stimulation also improved locomotor coordination and accelerated bone healing. In the dorsal root ganglia, vagal stimulation inhibited the activation of glial fibrillary acidic protein-positive satellite cells but without affecting microglial activation. Overall, these data provide novel evidence supportive of the use of pVNS to prevent postoperative pain and inform translational studies to test antinociceptive effects of bioelectronic medicine in the clinic.

Circulating levels of urocortin neuropeptides are impaired in children with overweight

ObjectiveThe corticotropin‐releasing factor neuropeptides (corticotropin‐releasing hormone [CRH] and urocortin [UCN]‐1,2,3) and spexin contribute to the regulation of energy balance and inhibit food intake in mammals. However, the status of these neuropeptides in children with overweight has yet to be elucidated. This study investigated the effect of increased body weight on the circulating levels of these neuropeptides.MethodsA total of 120 children with a mean age of 12 years were enrolled in the study. Blood samples were collected to assess the circulating levels of neuropeptides and were correlated with various anthropometric, clinical, and metabolic markers.ResultsPlasma levels of UCNs were altered in children with overweight but less so in those with obesity. Furthermore, the expression pattern of UCN1 was opposite to that of UCN2 and UCN3, which suggests a compensatory effect. However, no significant effect of overweight and obesity was observed on CRH and spexin levels. Finally, UCN3 independently associated with circulating zinc‐alpha‐2‐glycoprotein and UCN2 levels, whereas UCN1 was strongly predicted by TNFα levels.ConclusionsSignificant changes in neuropeptide levels were primarily observed in children with overweight and were attenuated with increased obesity. This suggests the presence of a compensatory mechanism for neuropeptides to curb the progression of obesity.

Social Transitions Cause Rapid Behavioral and Neuroendocrine Changes.

In species that form dominance hierarchies, there are often opportunities for low-ranking individuals to challenge high-ranking ones, resulting in a rise or fall in social rank. How does an animal rapidly detect, process, and then respond to these social transitions? This article explores and summarizes how these social transitions can rapidly (within 24 h) impact an individual's behavior, physiology, and brain, using the African cichlid fish, Astatotilapia burtoni, as a model. Male A. burtoni form hierarchies in which a few brightly-colored dominant males defend territories and spawn with females, while the remaining males are subordinate, more drab-colored, do not hold a territory, and have minimal opportunities for reproduction. These social phenotypes are plastic and reversible, meaning that individual males may switch between dominant and subordinate status multiple times within a lifetime. When the social environment is manipulated to create males that either ascend (subordinate to dominant) or descend (dominant to subordinate) in rank, there are rapid changes in behavior, circulating hormones, and levels of gene expression in the brain that reflect the direction of transition. For example, within minutes, males ascending in status show bright coloration, a distinct eye-bar, increased dominance behaviors, activation of brain nuclei in the social behavior network, and higher levels of sex steroids in the plasma. Ascending males also show rapid changes in levels of neuropeptide and steroid receptors in the brain, as well as in the pituitary and testes. To further examine hormone-behavior relationships in this species during rapid social ascent, the present study also measured levels of testosterone, 11-ketotestosterone, estradiol, progestins, and cortisol in the plasma during the first week of social ascent and tested for correlations with behavior. Plasma levels of all steroids were rapidly increased at 30 min after social ascent, but were not correlated with behavior during the initial rise in rank, suggesting that behavior is dissociated from endocrine status. These changes during social ascent are then compared with our current knowledge about males descending in rank, who rapidly show faded coloration, decreased dominance behaviors, increased subordinate behaviors, and higher circulating levels of cortisol. Collectively, this work highlights how the perception of similar social cues that are opposite in value are rapidly translated into adaptive behavioral and neuroendocrine changes that promote survival and reproductive fitness. Finally, future directions are proposed to better understand the mechanisms that govern these rapid changes in social position.

Differential gene expression in mutant mice overexpressing or deficient in the serotonin transporter: A focus on urocortin 1

Transcriptome analyses were performed in the anterior raphe area of mutant mice deficient in the serotonin transporter (5-HTT KO) or overexpressing this protein (5-HTT TG), which exhibit opposite changes in anxiety-related behavior. Among genes with altered expression, the gene encoding the neuropeptide urocortin 1 was down-regulated in 5-HTT KO and up-regulated in 5-HTT TG mice. Expression of the gene encoding cocaine-and-amphetamine-related-peptide, which colocalizes with urocortin 1, was also increased in 5-HTT TG mutants. Real-time RT-PCR confirmed these data and immunoautoradiographic labeling showed that parallel changes in neuropeptide levels were confined to the non-preganglionic Edinger–Westphal nucleus. Thus, 5-HTT expression correlates with that of urocortin 1, suggesting that this peptide can be involved in the behavioral changes observed in 5-HTT mutant mice.

Effect of Memantine on the Levels of Neuropeptides and Microglial Cells in the Brain Regions of Rats with Neuropathic Pain

Neuropathic pain induced by sciatic nerve injury not only causes peripheral dysfunctions but also affects the cortical and subcortical regions of the brain. It is still unknown whether neuropathic pain could relate to behavioral and neurochemical alterations in the central nervous system. This paper deals with the effect of peripheral neuropathic pain on mechanical allodynia, neuropeptide levels, neuropeptide-degrading enzyme activities, and microglial cells in the brain regions of rats by applying chronic constriction injury, a partial sciatic nerve injury. We examined the possible protection effect on the allodynia and changes in levels of neuropeptides and microglial activation in chronic constriction injury of the rat brain by memantine. On 4 days after chronic constriction injury, the induction of mechanical allodynia was suppressed by memantine treatment. Reductions in the substance P in the hypothalamus and somatostatin in the periaqueductal gray of chronic constriction injury rat brain were reversed by memantine. This suggests the role of these neuropeptides in pain information processing in the brain. Immunohistochemical experiments revealed that the expression of CD11b, a marker protein of microglia, was increased in the hypothalamus and periaqueductal gray in the chronic constriction injury rat brain as compared with the controls, and memantine treatment could suppress the activation of microglia, suggesting the involvement of microglia in pain mechanism. The present behavioral, biochemical, and immunohistochemical studies demonstrated that peripheral neuropathic pain affects the neuropeptide levels and microglial activation in the brain regions, and these events described above may play an important role in neuropathic pain pathogenesis.

Cocaine‐ and amphetamine‐regulated transcript is increased in Huntington disease

Weight loss and anxiety frequently occur in individuals with Huntington's disease (HD) but the underlying mechanisms are not well-understood. Peptides produced in the hypothalamus are involved in regulating energy homeostasis and emotion. Recent data suggest that changes in neuropeptide levels may be reflected in the cerebrospinal fluid (CSF), and could therefore serve as biomarkers for HD. Cocaine- and amphetamine-regulated transcript (CART) is a neuropetide expressed in several brain regions such as the hypothalamus, amygdala, and hippocampus. CART has been shown to increase anxiety and reduce food intake in rodents by as yet unknown mechanisms. Individuals with a CART mutation exhibit increased anxiety. In cross-sectional CSF samples from HD patients (n = 39), we found that levels of CART peptide were significantly increased by 23% compared to control subjects (n = 28). Increased CART levels in HD therefore hold promise as a biomarker as well as a potential pathogenic mediator of symptoms.

Peptidomics of Cpe<sup>fat/fat</sup> Mouse Hypothalamus and Striatum: Effect of Chronic Morphine Administration

Chronic morphine administration is known to affect several neuropeptide systems, and this could contribute to the behavioral effects of opiates. To quantitate global changes in neuropeptide levels upon chronic morphine administration, we took advantage of a method that allows selective isolation of neuropeptides from brains of mice lacking carboxypeptidase E (Cpefat/fat mice), a critical enzyme in the generation of many neuroendocrine peptides. We used a differential labeling procedure with stable isotopic tags and mass spectrometry to quantitate the relative changes in a number of hypothalamic and striatal peptides in Cpefat/fat mice chronically treated with morphine. A total of 27 distinct peptides were detected in hypothalamus and striatum. Of these, 27 were identified by mass spectrometry-based sequencing, 1 was tentatively identified by the mass and charge, and 9 were not identified. The identified peptides included fragments of proenkephalin, prothyrotropin-releasing hormone, secretogranin II, chromogranin Aand B, protachykinin B, provasopressin, promelanin concentrating hormone, and pro-SAAS. Upon morphine administration, although the levels of most of the peptides were unaltered (within a factor of 1.3 to 0.7 compared with saline control), the levels of a small number of peptides did show consistent changes (increased or decreased by 1.3-fold or more) in hypothalamus and/or striatum. Taken together, these results provide interesting insights into endogenous neuropeptide systems that are modulated by morphine and suggest further experiments to link candidate peptides with long-term effects of morphine.

Monitoring Plasma Neuropeptide-Like Immunoreactivity Levels in a Patient Given Hange-koboku-to for a Week for Swallowing Reflex Disorder

Hange-koboku-to (Banxia-houpo-tang), a Traditional Chinese Medicine remedy, has been used to treat swallowing reflex disorder, and it has been recently suggested that one of the mechanisms for the empirical effect of Hange-koboku-to involves humoral changes in neuropeptide levels. We suggested to administer Hange-koboku-to to a 70-year-old man with swallowing reflex disorder due to multiple cerebral infarctions and investigated the relationship between changes in plasma-neuropeptide-like immunoactivity (LI) levels and swallowing for a period of 1 week. On the 4 th and 7 th day of administration, the patient' s plasma calcitonin gene-related peptide (CGRP) -LI levels were twice the concentration on day 0 and Hange-koboku-to had increased the patient' s plasma substance P-LI levels approximately 5-fold on these 2 days. The plasma substance P-LI levels on days 4 and 7 were close to the levels (mean±SD) of elderly subjects without swallowing reflex disorder. Following the administration of Hange-koboku-to, plasma somatostatin-LI and vasoactive intestinal polypeptide (VIP) -LI levels in this patient exceeded those of elderly subjects without swallowing reflex disorder (mean + SD). With regard to symptoms, the patient' s difficulty in swallowing had disappeared on the third day of administration.This study suggests that Hange-koboku-to relieves swallowing reflex disorder by stimulating neuropeptidergic nerves and that this effect is achieved within 1 week of administration. However, we need to study more cases of the use of Hange-koboku-to for swallowing reflex disorder and further investigate the relationship between changes in neuropeptide-LI levels and its pharmacological effects.

Effects of Ninjin-to on Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

The herbal medicine Ninjin-to has been used for the treatment of gastroenteritis, esogastritis, gastric atony, gastrectasis, vomiting, and anorexia. One of the mechanisms of the empirical effects is assumed to be due to local changes in neuropeptide levels. Sensory afferent neurons in the gastrointestinal mucosa regulate neuropeptides [calcitonin gene-related peptide (CGRP), substance P, etc.], which play various physiologic roles. To determine whether the pharmacologic effects of Ninjin-to on the gastrointestine are due to changes in gastrointestinal mucosa regulatory peptide levels, we examined the effects of Ninjin-to on the levels of CGRP-like immunoreactive substances (IS) and substance P-IS in plasma taken from five healthy subjects. A single oral administration of 6.0 g of Ninjin-to caused significant increases in plasma CGRP-IS at 40 min and 60 min, and in substance P-IS levels at 90 min, compared with a placebo group. These results may indicate that the pharmacologic actions of Ninjin-to are closely related to changes in CGRP-IS and substance P-IS levels.

Quantitation of neuropeptides in Cpe(fat)/Cpe(fat) mice using differential isotopic tags and mass spectrometry.

Neuroendocrine peptides play important roles as intercellular messengers. We previously developed a technique to isolate and identify a large number of neuroendocrine peptides from Cpe(fat)/Cpe(fat) mice (Che, F.; et al. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 9971-6); these mice lack carboxypeptidase E activity and this defect causes an accumulation of neuropeptide intermediates that contain C-terminal Lys or Arg residues (Naggert, J. K.; et al. Nat. Genet. 1995, 10, 135-42). In the present study, we have developed a differential isotopic-labeling technique that can be used to quantitate changes in neuropeptide levels in Cpe(fat)/Cpe(fat) mouse tissues. Samples are treated with either the H6 or the D6 form of acetic anhydride, peptides that contain C-terminal basic amino acids are isolated by affinity chromatography on anhydrotrypsin agarose, and the isolated peptides are analyzed by mass spectrometry. Measurement of the regulation of pituitary peptides in response to dehydration showed a decrease in vasopressin. The general method described in this report should be widely applicable to a large number of neuroendocrine peptides, known and novel, in a variety of regulatory paradigms.

Processing of neuropeptide Y, galanin, and somatostatin in the cerebrospinal fluid of patients with Alzheimer’s disease and frontotemporal dementia

Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are two prevalent neurodegenerative disorders for which the causes are unknown, except in rare familial cases. Several changes in neuropeptide levels as measured by radioimmunoassay (RIA) have been observed in these illnesses. Somatostatin (SOM) levels in cerebrospinal fluid (CSF) are consistently decreased in AD and FTD. Neuropeptide Y (NPY) levels are decreased in AD, but normal in FTD. Galanin (GAL) levels increase with the duration of illness in AD patients. The majority of studies of neuropeptides in CSF have not been verified by HPLC. The observed decrease in a neuropeptide level as measured by RIA may therefore reflect an altered synthesis or extracellular processing, resulting in neuropeptide fragments that may or may not be detected by RIA. Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-MS) has been shown to be a powerful technique in the analysis of biological materials without any pre-treatment, by detecting peptides and proteins at a specific mass-to-charge (m/z) ratio. We studied the processing of the neuropeptides NPY [1–36], NPY [18–36], SOM [1–28] and GAL [1–30] in the cerebrospinal fluid of patients with AD ( n = 3), FTD ( n = 3) and controls ( n = 2) using MALDI-MS. We found that considerable inter-individual variability exists in the rate of neuropeptide metabolism in CSF, as well as the number of peptide fragments formed. Certain patients showed differences in the processing of specific neuropeptides, relative to other patients and controls. This analysis of the metabolic processing of neuropeptides in CSF yielded a large amount of data for each individual studied. Further studies are required to determine the changes in neuropeptide processing that can be associated with AD and FTD. With further investigations using MALDI-MS analysis, it may be possible to identify a neuropeptide fragment or processing enzyme that can be correlated to these disease states.

Basal levels and alcohol-induced changes in nociceptin/orphanin FQ, dynorphin, and enkephalin levels in C57BL/6J mice

In order to investigate the involvement of the opioid and nociceptin/orphanin FQ (N/OFQ) system in alcohol drinking behaviour, N/OFQ and the opioid peptides dynorphin B (DYNB) and Met-enkephalin-Arg 6 Phe 7 (MEAP) were examined in the alcohol-preferring C57BL/6J mice. Basal peptide levels were compared in the brain and the pituitary gland with basal levels in the alcohol-avoiding DBA/2J mice. Furthermore, the effects of chronic alcohol self-administration on peptides were studied in the C57BL/6J mice. Compared to the DBA/2J mice, C57BL/6J mice had low immunoreactive (ir) levels of DYNB and MEAP in the nucleus accumbens, the hippocampus, and the substantia nigra, low ir-DYNB levels in the striatum and low ir-MEAP levels in the frontal cortex. Higher ir-DYNB levels in the pituitary gland and in the periaqueductal gray (PAG) and higher ir-N/OFQ levels in the frontal cortex and in the hippocampus were detected in C57BL/6J mice compared to the DBA/2J mice. After 4 weeks of voluntary alcohol consumption, only minor changes in steady-state peptide levels were identified. However, 5 days after the alcohol-drinking period, lower levels of all peptides were detected in the ventral tegmental area and ir-DYNB levels were also lower in the amygdala and in the substantia nigra. Twenty-one days after cessation of alcohol self-administration, the opioid peptides in alcohol-consuming C57BL/6J mice were lower in the PAG, the N/OFQ was lower in the frontal cortex and DYNB was higher in the amygdala and substantia nigra as compared to control C57BL/6J mice. This study demonstrates strain differences between C57BL/6J mice and DBA/2J mice that could contribute to divergent drug-taking behaviour, and it also demonstrates time- and structure-specific changes in neuropeptide levels after alcohol self-administration in the C57BL/6J mice.

Chronic Exposure to Hypergravity Affects Thyrotropin-Releasing Hormone Levels in Rat Brainstem and Cerebellum

In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (β-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.

Abnormal neuropeptide concentration in rectal mucosa of patients with inflammatory bowel disease.

Regulatory neuropeptides are widely distributed in the gastrointestinal tract, where they play an important role in motility, secretion, and immune and inflammatory responses. In this study, the rectal mucosal content of somatostatin (SOM), substance P (SP), beta-endorphin (BE), and thyrotropin-releasing hormone (TRH) was measured by radioimmunoassay in 56 patients with ulcerative colitis (UC), 15 patients with Crohn's disease (CD), 15 patients with acute infectious colitis (AIC), and 11 controls, who showed no inflammation of the rectal mucosa, nor abnormal bowel movements. The content of immunoreactive (ir)-SOM was decreased in UC patients, especially in those with persistent disease activity, while the levels of ir-SP, BE, and TRH were increased in such patients. Some changes of ir-peptide levels were also observed in CD and AIC patients. The changes in neuropeptide levels were analyzed in relation to histological grades of inflammation in UC patients, grades 4-5 showing the most significant changes. The levels of ir-SOM, SP, BE, and TRH showed no significant change in chronic persistent UC when measured 6-12 months after the initial examination. In contrast, in patients with remitting intermittent UC, the levels of SP and BE decreased during remission. Abnormal intestinal neuropeptide content may be implicated in the continued mucosal immune and inflammatory responses that are manifested in patients with inflammatory bowel disease.

Changes in neuropeptide levels after brain damage in rats.

The physiological and pathophysiological roles of neuropeptides are still not clear. The aim of our study was to detect long lasting changes of vasoactive-intestinal peptide (VIP), somatostatin (SOM) and substance P (SP) contents in the rat cerebral cortex and hippocampus after brain lesion. The experiments were performed on groups of adult male Wistar rats. The first group consisted of animals with unilateral ablation of the sensorimotor cortex performed at the age of 60 days. The second group was a control one (rats of the same age but with an intact brain). Both groups of animals were sacrificed at the age of 90-105 days and radioimmunoassay was used to determine amounts of VIP, SOM and SP. The mean values of VIP levels were decreased significantly only in contralateral cortical areas, while there was an increase of SP in lesioned animals. Our results suggest that descrete changes in neuropeptide levels occur during restorative processes after brain lesion.

Time course of changes in neuropeptide levels after surgical and experimental interventions in the rat small intestine

Time course of changes in neuropeptide levels after surgical and experimental interventions in the rat small intestine

Regional changes in neuropeptide levels after 5,7-dihydroxytryptamine-induced serotonin depletion in the rat brain.

The levels of five neuropeptides (substance-P, somatostatin, cholecystokinin octapeptide, methionine-enkephalin and dynorphin) were examined in the brain and the spinal cord of rats 2 weeks after intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT). 5,7-DHT injection caused a significant reduction of the serotonin level in all regions of the brain. The level of each neuropeptide except dynorphin significantly increased in specific regions of the brain after 5,7-DHT treatment without any decrease in their levels in any region. Since, coexistence and interaction between classical neurotransmitters and neuropeptides in the same neurons have been reported, both are indispensable for evaluating pathophysiological state of the brain function associated with abnormal neural transmission. The present findings together with previous reports suggest that neuropeptides act as neurotransmitters and compensate for the impaired function of the serotonergic systems.

Elevated Activities of Lipases and Lysophospholipase in Alzheimer's Disease

Two plasma membrane fractions were obtained from different regions of brains from patients with Alzheimer''s disease (AD) and normal aged individuals. One fraction was from synaptosomes (synaptosomal plasma membrane; SPM) and the other from glial cells and neuronal cell bodies (plasma membrane; PM). Among various regions analyzed, PM and SPM from the nucleus basalis of AD brains displayed 6- to 8-fold higher activities of mono- and diacylglycerol lipases than membranes from age-matched normal individuals. Membranes from the hippocampus region of AD brains also showed consistently higher activities of lipases than those from control brains. Similarly, the lysophospholipase activity in the cytosolic fraction of these regions also showed higher activity (4- to 6-fold) in AD than in corresponding fractions from normal human brains. The cause of increased activities of lipases and lysophospholipases in the nucleus basalis and hippocampus regions is not understood. However, marked elevations of acylhydrolases in the above regions may be due to overexpression, changes in levels of neuropeptides, intracellular calcium ions and/or lipid peroxides. All these are known to stimulate acylhydrolases. Autolytic changes which occur in the brain after death may markedly affect the activities of mono- and diacylglycerol lipases.

Differential steroid hormone and neural influences on peptide mRNA levels in CRH cells of the paraventricular nucleus: A hybridization histochemical study in the rat

The three major classes of neurons in the paraventricular nucleus (PVH) provide a rich model for studying hormonal and neural influences on multiple neuropeptides expressed in individual cells. A great deal of previous work has examined this problem at the immunohistochemical level, where hormonal and neural influences on peptide levels have been established. In situ hybridization methods were used here to determine whether these effects are accompanied by measurable changes in neuropeptide mRNA levels. In the first series of experiments, the time-course of corticosterone replacement effects on corticotropin-releasing hormone (CRH) mRNA levels in parvicellular neuroendocrine cells of adrenalectomized animals were determined, and a dose-response curve was established. CRH mRNA hybridization remains maximal with plasma levels of steroid up to about 50 ng/ml, then declines sharply between about 60-130 ng/ml, and is just detectable at higher levels. We confirmed that corticosterone decreases vasopressin mRNA levels in this cell group and showed that levels of preproenkephalin mRNA are also decreased, whereas no significant changes in cholecystokinin, beta-preprotachykinin, and angiotensinogen mRNA levels could be detected. Thus, corticosterone decreases some neuropeptide mRNA levels and has no influence on others in this cell group. Tyrosine hydroxylase mRNA hybridization is also unaffected in this part of the nucleus. In a second group of experiments, the cell-type specificity of corticosterone influences was examined. It was found that while the hormone depresses CRH mRNA levels in parvicellular neurons, it increases such levels in PVH neurons with descending projections, in certain magnocellular neurosecretory neurons, and in a part of the central nucleus of the amygdala, whereas no influence was detected in the rostral lateral hypothalamic area. Furthermore, the stimulatory effects of corticosterone have different threshold levels in different cell groups. Thus, in different types of neurons, corticosterone may increase, decrease, or have no influence on CRH mRNA levels. In contrast, while corticosterone depresses vasopressin mRNA levels in parvicellular CRH neurons, it has no obvious effects on vasopressin mRNA levels in magnocellular or descending neurons; as with CRH, the effects of corticosterone on vasopressin mRNA levels are cell-type specific. In a third series of experiments it was shown that glucocorticoid receptor and mineralocorticoid receptor mRNAs are found in all three cell types in the PVH and that corticosterone tends to produce modest increases in mRNA levels for both receptors. Finally, it was shown that unilateral catecholamine-depleting knife cuts do not change mRNA levels for any of the neuropeptides (or steroid hormone receptors) examined here, although dramatic changes in neuropeptide levels themselves have been shown.4+

Effects of hemorrhage and opiate antagonists on adrenal release of neuropeptides in cats

Concurrent levels of methionine-enkephalin (ME), neuropeptide Y (NPY), peptide YY (PYY), neurotensin (NT), vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK) and bombesin (BMB) were measured in adrenal vein (AD), femoral vein (FV) and femoral artery (FA) under baseline conditions and during hypotensive hemorrhage (HTH) in halothane anesthetized cats (Group II, n=6) and compared to a non-bled control group (Group I, n=6). Five cats (Group III) received an IV bolus of naltrexone (1 mg/kg) followed by a continuous infusion prior to induction of HTH. A blood volume loss of ∼40% evoked a selective increase in AD levels of ME, NPY, PYY and NT. No differences in regard to hemodynamics and pattern of neuropeptide levels were observed between Group II and Group III. Administration of naloxone (1 mg/kg, IV) in Group I and Group II at the end of the experiment led to a significant increase in MABP in both groups but did not evoke changes in neuropeptide levels. We conclude that adrenal neuropeptide release during hypotensive hemorrhage is not modulated by actions on opiate receptors in the halothane anesthetized cat.