Somatostatin-like Immunoreactivity Research Articles

Changes in the Levels of Neuropeptides and Their Metabolizing Enzymes in the Brain Regions of Nucleus Basalis Magnocellularis-Lesioned Rats

The regulation mechanism of the interrelation between neuropeptides and their metabolizing enzymes in in vivo tissues is still not clear. In the present report, we attempted to measure the levels of neuropeptides and their enzymes in the frontal cortex, hippocampus, and striatum of the rat that had been bilaterally lesioned by the infusion of ibotenic acid or amyloid β-peptide 25 – 35 (Aβ25 – 35) into the nucleus basalis magnocellularis. In the drug-treated rats, at two weeks after the infusion, the decrease of somatostatin-like immunoreactivity (SS-LI) and the increase of cholecystokinin-8S-LI were found in some brain regions relative to vehicle-treated rats. The immunoreactivities of endopeptidase 24.15 and puromycin-sensitive aminopeptidase and the leucine aminopeptidase- and aminopeptidase B-like enzyme activities did not change in the three brain regions, suggesting that the levels of those peptide-degrading enzymes do not correlate with the changes of the neuropeptide levels. The decrease of subtilisin-like proprotein convertase (SPC)-like enzyme activity was found in the hippocampus of the Aβ25 – 35-treated rats. The SS mRNA level decreased in the hippocampus in parallel with decreases in the SS-LI level and SPC-like enzyme activity. The present data indicate that some of the neuropeptide-processing enzymes may contribute to the control of neuropeptide levels.

Central [CNS] and Peripheral [Gastric Tissue] Selective Monitoring of Somatostatin (SRIF) with Micro-Sensor and Voltammetry in Rats: Influence of Growth Factors (GH, EGF).

Somatostatin (SRIF) is widely distributed throughout the body, and regulates the endocrine system via interactions with various hormones, including the pituitary growth hormone, the thyroid stimulating hormone and the majority of the hormones of the gastrointestinal tract. SRIF is present in the central nervous system (CNS), where it affects rates of neurotransmission, and is also reported to be active in the intestinal tract, with evidence that stressed rats present a significant decrease in antral somatostatin-like immunoreactivity (SLI). Analysis of SRIF has mainly been carried out by means of radioimmunoassay methods. Here, we propose the use of an electrochemical method, such as voltammetry, applied with carbon-based sensors and, in particular, the combination of differential pulse voltammetry with treated carbon fiber micro electrodes (DPV-µCFE) to facilitate the analysis of such peptidergic electro active hormones in the rat striatum and gastric tissue; the effect of growth hormone (GH) and epidermal growth factor (EGF), in particular, upon the SRIF signal has been studied in such tissues.

Evidence for a novel, neurohumoral antinociceptive mechanism mediated by peripheral capsaicin-sensitive nociceptors in conscious rats

Stimulation of capsaicin-sensitive peripheral sensory nerve terminals induces remote anti-inflammatory effects throughout the body of anesthetized rats and guinea-pigs mediated by somatostatin. As somatostatin has also antinociceptive effects, the study aimed at investigating whether similar remote antinociceptive effects can be demonstrated in awake animals.In conscious rats, nociceptive nerve endings of the right hind paw decentralized by cutting the sciatic and saphenous nerves 18h before were chemically stimulated, and drop of the noxious heat threshold (heat hyperalgesia) induced by prior (18h before) plantar incision was measured on the contralateral, left hind paw using an increasing-temperature water bath. 18h after nerve transection, mustard oil-evoked plasma extravasation was not significantly reduced in the right hind paw as tested by in vivo fluorescence imaging. Applying agonist of either transient receptor potential vanilloid 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1) receptor (capsaicin or mustard oil, respectively) to the nerve-transected paw inhibited the plantar incision-induced drop of the noxious heat threshold on the contralateral paw. The onset of these remote antihyperalgesic effects was 10–20min. A similar contralateral inhibitory effect of capsaicin or mustard oil treatment was observed on neuropathic mechanical hyperalgesia evoked by partial sciatic nerve injury 2days before nerve transection and measured by a Randall–Selitto apparatus. The remote thermal antihyperalgesic effect was prevented by chronic (5days) denervation or local capsaicin desensitization of the stimulated paw; reduced by intraperitoneally applied antagonist of somatostatin (cyclosomatostatin) or opioid receptors (naloxone). The response was mimicked by intraperitoneally applied somatostatin and associated with a 72±27% increase in plasma somatostatin-like immunoreactivity that was absent after chronic (5days) denervation.In conclusion, chemical activation of decentralized peripheral capsaicin-sensitive nociceptors evokes remote antihyperalgesic responses initiated outside the central nervous system and mediated by somatostatin and endogenous opioids.

Changes in Somatostatin-Like Immunoreactivity in the Sympathetic Neurons Projecting to the Prepyloric Area of the Porcine Stomach Induced by Selected Pathological Conditions.

The aim of the present study was to define changes in the expression of somatostatin (SOM) in the sympathetic perikarya innervating the porcine stomach prepyloric area during acetylsalicylic-acid-induced gastritis (ASA) and experimentally induced hyperacidity (HCL) and following partial stomach resection (RES). On day 1, the stomachs were injected with neuronal retrograde tracer Fast Blue (FB). Animals in the ASA group were given acetylsalicylic acid orally for 21 days. On the 22nd day after FB injection, partial stomach resection was performed in RES animals. On day 23, HCL animals were intragastrically given 5 ml/kg of body weight of a 0.25 M aqueous solution of hydrochloric acid. On day 28, all pigs were euthanized. Then, 14-μm thick cryostat sections of the coeliac-superior mesenteric ganglion (CSMG) complexes were processed for routine double-labelling immunofluorescence. All pathological conditions studied resulted in upregulation of SOM-like (SOM-LI) immunoreactivity (from 14.97 ± 1.57% in control group to 33.72 ± 4.39% in the ASA group, to 39.02 ± 3.65% in the RES group, and to 29.63 ± 0.85% in the HCL group). The present studies showed that altered expression of SOM occurs in sympathetic neurons supplying the prepyloric area of the porcine stomach during adaptation to various pathological insults.

RARβ regulates neuronal cell death and differentiation in the avian ciliary ganglion.

ABSTRACTProgrammed cell death during chicken ciliary ganglion (CG) development is mostly discussed as an extrinsically regulated process, guided either by the establishment of a functional balance between preganglionic and postganglionic activity or the availability of target‐derived neurotrophic factors. We found that the expression of the gene coding for the nuclear retinoic acid receptor β (RARB) is transiently upregulated prior to and during the execution phase of cell death in the CG. Using retroviral vectors, the expression of RARB was knocked down during embryonic development in ovo. The knockdown led to a significant increase in CG neuron number after the cell death phase. BrdU injections and active caspase‐3 staining revealed that this increase in neuron number was due to an inhibition of apoptosis during the normal cell death phase. Furthermore, apoptotic neuron numbers were significantly increased at a stage when cell death is normally completed. While the cholinergic phenotype of the neurons remained unchanged after RARB knockdown, the expression of the proneural gene Cash1 was increased, but somatostatin‐like immunoreactivity, a hallmark of the mature choroid neuron population, was decreased. Taken together, these results point toward a delay in neuronal differentiation as well as cell death. The availability of nuclear retinoic acid receptor β (RARβ) and RARβ‐induced transcription of genes could therefore be a new intrinsic cue for the maturation of CG neurons and their predisposition to undergo cell death. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1204–1218, 2015

Capsaicin-sensitive sensory nerves exert complex regulatory functions in the serum-transfer mouse model of autoimmune arthritis.

The K/BxN serum-transfer arthritis is a widely-used translational mouse model of rheumatoid arthritis, in which the immunological components have thoroughly been investigated. In contrast, little is known about the role of sensory neural factors and the complexity of neuro-immune interactions. Therefore, we analyzed the involvement of capsaicin-sensitive peptidergic sensory nerves in autoantibody-induced arthritis with integrative methodology. Arthritogenic K/BxN or control serum was injected to non-pretreated mice or resiniferatoxin (RTX)-pretreated animals where capsaicin-sensitive nerves were inactivated. Edema, touch sensitivity, noxious heat threshold, joint function, body weight and clinical arthritis severity scores were determined repeatedly throughout two weeks. Micro-CT and in vivo optical imaging to determine matrix-metalloproteinase (MMP) and neutrophil-derived myeloperoxidase (MPO) activities, semiquantitative histopathological scoring and radioimmunoassay to measure somatostatin in the joint homogenates were also performed. In RTX-pretreated mice, the autoantibody-induced joint swelling, arthritis severity score, MMP and MPO activities, as well as histopathological alterations were significantly greater compared to non-pretreated animals. Self-control quantification of the bone mass revealed decreased values in intact female mice, but significantly greater arthritis-induced pathological bone formation after RTX-pretreatment. In contrast, mechanical hyperalgesia from day 10 was smaller after inactivating capsaicin-sensitive afferents. Although thermal hyperalgesia did not develop, noxious heat threshold was significantly higher following RTX pretreatment. Somatostatin-like immunoreactivity elevated in the tibiotarsal joints in non-pretreated, which was significantly less in RTX-pretreated mice. Although capsaicin-sensitive sensory nerves mediate mechanical hyperalgesia in the later phase of autoantibody-induced chronic arthritis, they play important anti-inflammatory roles at least partially through somatostatin release.

Analgesic topical capsaicinoid therapy increases somatostatin-like immunoreactivity in the human plasma

The aim of the present study was to evaluate the therapeutic potential of local capsaicinoid (EMSPOMA® cream) treatment on chronic low back pain in patients with degenerative spine diseases and to investigate the possible mechanism of action of the therapy.The qualitative and quantitative analyses of capsaicinoids in EMSPOMA® cream were performed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). In the clinical study 20 patients with degenerative spine diseases were involved in a self-controlled examination. During the 21 day therapy they received 30 min daily treatment with capsaicinoid (EMSPOMA®) cream to the lumbar region of the back. The pain (VASs, Oswestry Disability Index) and the mobility of the lumbar region of the spine (Schober's, Domján's L and R test) were detected at baseline and at the end of the 1st, 2nd and 3rd weeks. The plasma level of somatostatin-like immunoreactivity (SST-LI) was measured by radioimmunoassay (RIA) before and after the treatment on the first and the last day of the therapy.Nonivamide (0.01%) was identified as the only capsaicinoid molecule in the cream. In the clinical study the 21 day local nonivamide treatment reduced the pain sensation. Oswestry Disability Index decreased from 39 ± 3.9% to 32.5 ± 4.4%. VASs showed 37.29%–59.51% improvement. In the plasma level of SST-LI threefold elevation was observed after the first nonivamide treatment.We conclude that nonivamide treatment exerts analgesic action in chronic low back pain and causes the release of the antinociceptive and anti-inflammatory neuropeptide somatostatin which may play pivotal role in the pain-relieving effect.

Plasma somatostatin-like immunoreactivity increases in the plasma of septic patients and rats with systemic inflammatory reaction: Experimental evidence for its sensory origin and protective role

Alterations of somatostatin-like immunoreactivity (SST-LI) in the plasma of 11 systemic inflammatory response syndrome (SIRS) patients were investigated in correlation with cytokines, adhesion molecules and coagulation markers repeatedly during 4 days. The origin and role of SST were studied in the cecum ligation and puncture (CLP) rat SIRS model. Capsaicin-sensitive peptidergic sensory nerves were defunctionalized by resiniferatoxin (RTX) pretreatment 2 weeks earlier, in a separate group animals were treated with the somatostatin receptor antagonist cyclo-somatostatin (C-SOM). Plasma SST-LI significantly elevated in septic patients compared to healthy volunteers during the whole 4-day period. Significantly decreased Horowitz score showed severe lung injury, increased plasma C-reactive protein and procalcitonin confirmed SIRS. Soluble P-selectin, tissue plasminogen activator and the interleukin 8 and monocyte chemotactic protein-1 significantly increased, interleukin 6 and soluble CD40 ligand did not change, and soluble Vascular Adhesion Molecule-1 decreased. SST-LI significantly increased in rats both in the plasma and the lung 6h after CLP compared to sham-operation. After RTX pretreatment SST-LI was not altered in intact animals, but the SIRS-induced elevation was absent. Lung MPO activity significantly increased 6h following CLP compared to sham operation, which was significantly higher both after RTX-desensitization and C-SOM-treatment. Most non-pretreated operated rats survived the 6h, but 60% of the RTX-pretreated ones died showing a significantly worse survival. This is the first comprehensive study in humans and animal experiments providing evidence that SST is released from the activated peptidergic sensory nerves. It gets into the bloodstream and mediates a potent endogenous protective mechanism.

Somatostatin as an Active Substance of Enteroendocrine Cells in the Canine Digestive Tract in Physiological Conditions and during Inflammatory Bowel Disease

The aim of the present investigation is to examine the changes in the number of somatostatin-like immunoreactive (SOM-LI) enteroendocrine cells in various parts of the canine gastrointestinal (GI) tract during canine inflammatory bowel disease (IBD). The distribution of SOM-LI enteroendocrine cells was studied using the double-labeling immunofluorescence technique with antisera against chromogranin A (CgA; used here as a marker of enteroendocrine cells) and somatostatin (SOM). Evaluation of the number of CgA-positive cells, which also contained SOM in the mucosal layer of canine stomach, duodenum, jejunum and descending colon was based on the counting of such cells per unit area (0.1 mm2). In physiological conditions, the number of SOM-LI enteroendocrine cells has been shown to constitute 5.30±2.07 in the stomach, 2.23±0.56 in the duodenum, 1.86±0.48 in the jejunum and 1.19±0.36 in the descending colon. Canine IBD caused an increase in the number of cells studied in the stomach (to 9.55±1.46) and the jejunum (to 3.84±1.16), while the changes observed in the duodenum and the descending colon have not been statistically significant. The obtained results suggest that SOM-LI enteroendocrine cells, as well as somatostatin, may be involved in pathological processes during canine IBD. Moreover, this study can be treated as the first step of application of SOM and/or its analogues in the treatment of canine IBD in the future.

The influence of selected pathological states on the somatostatin-like immunoreactive (SOM-LI) endocrine cells in the mucosal layer of the porcine descending colon

This study reports on changes in the number of somatostatin-like immunoreactive (SOM-LI) endocrine cells in the porcine descending colon, caused by chemically driven inflammation, axotomy and proliferative enteropathy (PE). The distribution pattern of SOM-LI endocrine cells has been studied using the routine single-labelling immunofluorescence technique. Semi-quantitative evaluation of the number of the SOM-immunostained endocrine cells within the mucosal layer of the porcine descending colon has been based on counting of all endocrine cells immunoreactive to SOM per unit area (0,1 mm²). Under physiological conditions the number of SOM-LI endocrine cells has been shown to constitute 3,30±0,22. All applied pathological processes resulted in changes in the SOM-like immunoreactivity, which varied in particular processes studied. The number of SOM-LI endocrine cells increased to 6,28±0,31 and 4,43±0,35 during chemically driven inflammation and proliferative enteropathy, respectively, and decreased to 1,17%±0,16 after axotomy. The obtained results suggest that SOM-LI endocrine cells may participate in various pathological states within porcine descending colon and their functions probably depend on the type of pathological factor.

Sulphurous medicinal waters increase somatostatin release: It is a possible mechanism of anti-inflammatory effect of balneotherapy in psoriasis

AimBalneotherapy has been used in the treatment of immune-mediated skin diseases, but its molecular mechanism has yet to be elucidated. The aim of the present study was to observe the effect of sulphurous medicinal water in a murine dermatitis model and on psoriatic patients; moreover to investigate the role of hydrogen sulphide in the release of somatostatin during bathing treatment. Materials and methodsInflammation was induced by oxazolone in the paw skin of mice. Oedema, TNF-α concentration, histological changes and myeloperoxidase level were investigated. Mice were bathed in medicinal water or distilled water for 20min/day. To define the effect of hydrogen sulphide on somatostatin release mice were bathed in sodium hydrosulphide solution for 2 weeks. Somatostatin plasma concentration was detected by nanoHPLC-ESI-Q-TOF-MS.In the clinical study nineteen patients (PASI: 2.2–21.6) received 2×25-min bath treatment for 21 days. Somatostatin-like immunoreactivity of the plasma was determined by radioimmunoassay. Before and after the balneotherapy skin biopsies were performed. ResultsOxazolone caused 29.43–33.73% paw swelling which was significantly reduced by the medicinal water. Myeloperoxidase, TNF-α levels and histological changes of the skin were unaltered. Somatostatin plasma concentration significantly increased in response to the bathing treatment.In the clinical study PASI markedly declined (0–13.4) and the plasma level of somatostatin increased significantly. Langerhans-cells migrated from the dermal pool to the epidermis. ConclusionWe conclude that balneotherapy is an effective treatment in psoriasis. Our results provided evidence that somatostatin released by H2S plays role in the mechanism of action of sulphurous medicinal water.

Inhibition of the Function of TRPV1-Expressing Nociceptive Sensory Neurons by Somatostatin 4 Receptor Agonism: echanism and Therapeutical Implications

Release of somatostatin into the circulation from the activated TRPV1-expressing nociceptors revealed by antidromic stimulation of dorsal roots in the rat pinpointed to a novel potential drug target on these nociceptors. The review summarizes the functional, biochemical and pharmacological evidence for a novel somatostatin-mediated counter-regulatory antiinflammatory/antinociceptive "sensocrine" function in rats and guinea-pigs. To identify the somatostatin receptor subtype(s) responsible for this function, experiments were focused on actions of sstR4 receptor agonists as this subtype, similarly to sstR1, is not involved in endocrine regulation. Involvement of somatostatin and the sstR4 was revealed by using pretreatment with somatostatin antibody, depletion of somatostatin with cysteamine, measuring the plasma somatostatin-like immunoreactivity, release from nerves in vitro from isolated trachea, detection of sstR4 receptors in animal and human tissue specimens, using sstR4 gene-deleted mice and investigating in detail effects of a stable peptide analogue of somatostatin (TT-232) and of an ultrapotent non-peptide agonist of sstR4 receptors. Promising antinociceptive, antihyperalgesic effects of these sstR4 agonists were observed in various experimental models of inflammatory and neuropathic conditions which are mediated both by TRPV1-expressing nociceptors and non-neural cells involved in mediation of inflammation. In sstR4 receptor knockout mice an aggravation of inflammation and hyperalgesia was observed.

Role of ethanolamine phosphate in the hippocampus of rats with acute experimental autoimmune encephalomyelitis

Here, we assessed the effects of acute experimental autoimmune encephalomyelitis (EAE) on the rat hippocampal somatostatinergic system and whether administration of an ethanolamine phosphate salt could prevent the appearance of the clinical signs and the impairment of the somatostatinergic system in this pathological condition. Female Lewis rats were injected in both hindlimb footpads with myelin basic protein from guinea pig brain and complete Freund's adjuvant and were sacrificed when limp tail (grade 1 EAE) or severe hindlimb paralysis (grade 3 EAE) were observed. One group was injected daily with ethanolamine phosphate, starting two days prior to immunization and for 15 days thereafter. The animals were sacrificed 15 days post-immunization. Acute EAE in grade 3 increased anti-myelin basic protein antibodies in rat serum as well as tumor necrosis factor-α and interferon-γ levels in hippocampal extracts. In addition, it decreased the somatostatin receptor density, somatostatin receptor subtype 2 mRNA and protein content, and the inhibitory effect of somatostatin on adenylyl cyclase activity in the hippocampus. The protein levels of the inhibitory G protein subunits αi 1–3, the G protein-coupled receptor kinase isoforms 2, 5 and 6, the phosphorylated cyclic AMP-binding protein and the somatostatin-like immunoreactivity content were unaltered in this brain area. Acute EAE in grade 1 did not modify any of these parameters. Ethanolamine phosphate administration prevented the clinical expression of acute EAE as well as the decrease in the somatostatin receptor density, somatostatin receptor subtype 2 expression and the capacity of somatostatin to inhibit adenylyl cyclase activity at the time-period studied. Furthermore, it blunted the rise in serum anti-myelin basic protein antibodies and hippocampal interferon-γ and tumor necrosis factor-α levels. Altogether, these data suggest that ethanolamine phosphate might provide protection against acute EAE.

Surgery and sepsis increase somatostatin-like immunoreactivity in the human plasma

We have previously shown in animals that somatostatin released from capsaicin-sensitive afferents in response to inflammation and tissue damage exerts systemic anti-nociceptive and anti-inflammatory actions. Since peptidergic sensory innervation of the airways and the joints are particularly dense, we aimed at investigating the alterations of plasma somatostatin-like immunoreactivity (SST-LI) in response to thoracic and orthopedic surgery, as well as sepsis. Thoracotomy, video-assisted thoracoscopy, hip and knee endoprosthesis were performed under general anesthesia. Blood was taken before, during and after the surgical procedures, as well as at admission and every consecutive morning from septic patients receiving exclusively total parenteral nutrition. SST-LI was determined from the plasma with specific and sensitive radioimmunoassay developed in our laboratory. Plasma SST-LI in healthy volunteers and preoperatively was 8–12 fmol/ml. Both thoracotomy and thoracoscopy significantly increased SST-LI by 55–60% at the end of the procedures when the thoracic cavity and the skin were closed. Hip endoprosthesis implantation elevated SST-LI by 30% after skin incision, which increased further to 55% by the time the surgery was completed. In contrast, knee operations performed under tourniquet did not alter SST-LI in the systemic circulation. SST-LI was almost 3-fold higher in the plasma of septic patients than in healthy volunteers. This human study revealed that thoracic/hip surgery and sepsis elevate SST-LI in the systemic circulation, presumably by inducing its release from sensory fibres. It is concluded, that the endogenous protective mechanism mediated by neural somatostatin, which has been evidenced in animals, is likely to operate in patients.

Changes in the somatostatin (SOM)-like immunoreactivity within nervous structures of the porcine descending colon under various pathological factors

This study reports on changes in the somatostatin-like immunoreactive (SOM-LI) nerve structures of the enteric nervous system (ENS) in the porcine descending colon, caused by chemically driven inflammation, proliferative enteropathy (PE), which is a “natural” inflammation with proliferative changes and nerve injury (axotomy). The distribution pattern of SOM-LI structures was studied using the immunofluorescence technique in the circular muscle layer, the myenteric (MP), outer submucous (OSP) and inner submucous plexuses (ISP) and also in the mucosal layer. Under physiological conditions SOM-LI perikarya have been shown to constitute 1.97 ± 0.36%, 2.06 ± 0.33% and 4.23 ± 0.40% in the MP, OSP and ISP, respectively. Changes in SOM-immunoreactivity depended on the pathological factor and the part of the ENS studied. Numbers of the SOM-LI perikarya amounted 1.81 ± 0.30, 1.97 ± 0.24 and 11.15 ± 0.95 during chemically induced colitis and 3.21 ± 0.37%, 4.33 ± 0.33% and 4.42 ± 0.32% after axotomy in MP, OSP and ISP, respectively. Moreover during PE SOM-positive cell bodies were not observed at all in MP, whereas within OSP and ISP the number of SOM-LI perikarya amounted to 3.34 ± 0.36 and 10.92 ± 059, respectively. All processes studied resulted in a decrease in the number of SOM-LI nerve fibers in the mucosal layer, whereas within the circular muscle layer chemically induced inflammation and axotomy caused an increase in the number of the SOM-LI nerve fibers contrary to PE, which reduced the number of such fibers. The obtained results suggest that SOM-LI nerve structures of the ENS may participate in various pathological states within the porcine descending colon and their functions probably depend on the type of pathological factor.

The cortistatin gene PSS2 rather than the somatostatin gene PSS1 is strongly expressed in developing avian autonomic neurons

Somatostatin and cortistatin are neuromodulators with divergent expression patterns and biological roles. Whereas expression and function of genes encoding somatostatin (PSS1) and the related peptide cortistatin (PSS2) have been studied in detail for the central nervous system (CNS) and immune system, relatively little is known about their expression patterns in the peripheral nervous system (PNS). We compare the expression patterns of PSS1 and PSS2 in chicken embryos. At E14, PSS1 is higher in the CNS versus PNS, whereas PSS2 is higher in the PNS. During early development, PSS1 is transiently expressed in lumbar sympathetic ganglia and is detectable at low levels throughout the development of dorsal root and ciliary ganglia. In contrast, PSS2 expression increases as development progresses in sympathetic and dorsal root ganglia, whereas levels in ciliary ganglia by E8 are more than 100-fold higher than in sympathetic ganglia. Activin, which induces somatostatin-like immunoreactivity in ciliary ganglion neurons in vivo and in vitro, controls PSS2 expression by stabilizing PSS2 but not PSS1 mRNA. We conclude that much of the somatostatin-like immunoreactivity in the developing avian peripheral nervous system is actually cortistatin, the PSS2 product, as opposed to true somatostatin, which is the PSS1 product. The identification of PSS2 as the predominantly expressed somatostatin gene family member in avian autonomic neurons provides a molecular basis for further functional and pharmacological studies.

Low-dose infusion of somatostatin in man--no effect upon intestinal calcium absorption but a fall in blood insulin.

We studied the role of low plasma somatostatin (SRIF) levels in intestinal calcium absorption (CaA) in man. Plasma somatostatin-like immunoreactivity (SLI; pg X ml-1) rose after a 600-cal test meal (from 22.9 +/- 2 basally to 30.6 +/- 3.6 at 45 min, p less than 0.05), but was not affected by an oral Ca load (264 mg). Under intravenous SRIF (0.15 microgram kg-1 h-1) plasma SLI rose from 3.3 +/- 0.4 basally to 24.5 +/- 3 at 45 min (p less than 0.001). CaA was not influenced under these conditions, whereas insulin levels fell significantly and the levels of PTH, calcitonin, glucagon and GH were not changed. A regulating role of SRIF in CaA seems therefore unlikely for human physiology, since neither SLI is influenced by an oral Ca load, nor is CaA changed under postprandial SLI. The fall in insulin under postprandial-like SLI levels favors the view of a hormonal role of SRIF in man.

Striatal Alterations of Secretogranin-1, Somatostatin, Prodynorphin, and Cholecystokinin Peptides in an Experimental Mouse Model of Parkinson Disease

The principal causative pathology of Parkinson disease is the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta projecting to the striatum in the brain. The information regarding the expression of neuropeptides in parkinsonism is very limited. Here we have elucidated striatal neuropeptide mechanisms in experimental parkinsonism using the unilateral 6-hydroxydopamine model to degenerate dopamine neurons. A thoroughly controlled sample preparation technique together with a peptidomics approach and targeted neuropeptide sequence collections enabled sensitive detection, identification, and relative quantitation of a great number of endogenous neuropeptides. Previously not recognized alterations in neuropeptide levels were identified in the unilateral lesioned mice with or without subchronic 3,4-dihydroxy-L-phenylalanine administration, the conventional treatment of Parkinson disease. Several of these peptides originated from the same precursor such as secretogranin-1, somatostatin, prodynorphin, and cholecystokinin. Disease-related biotransformation of precursors into individual peptides was observed in the experimental model of Parkinson disease. Several previously unreported potentially biologically active peptides were also identified from the striatal samples. This study provides further evidence that neuropeptides take part in mediating the central nervous system failure associated with Parkinson disease.

Regulation of Somatostatin Release by Adenosine in the Mouse Stomach

Adenosine inhibits gastric acid secretion, either directly by acting on acid-secreting parietal cells or indirectly by stimulating the release of the acid inhibitor, somatostatin. The present study examined the role of adenosine on somatostatin release in an isolated vascularly perfused mouse stomach model. Concentrations of exogenous adenosine >or= 1.0 microM stimulated gastric release of somatostatin-like immunoreactivity (SLI), and this effect was blocked by the A(2A) receptor antagonist ZM 241385 [4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol]. The A(2A) receptor agonist CGS 21680 [2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride] augmented SLI release in a concentration-dependent manner, suggesting that A(2A) receptor activation is involved in the stimulatory effect of adenosine on SLI release. Conversely, SLI release was inhibited by the A(1) receptor agonists N(6)-cyclopentyladenosine and 2-chloro-N(6)-cyclopentyladenosine and lower concentration of adenosine (0.01 microM). The involvement of specific adenosine receptors in controlling the release of gastric SLI was also examined using A(2A) receptor knockout (A(2A)R-KO) mice. In these mice, adenosine (10 microM) inhibited SLI release, and the effect was abolished by the selective A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, suggesting a link between the selective A(1) activation and inhibition of SLI release. The adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride augmented SLI release in wild-type controls but not in the presence of ZM 241385 or in A(2A)R-KO mice. We conclude that adenosine has dual actions on regulating mouse gastric SLI release: stimulatory at higher concentrations through the A(2A) receptor and inhibitory at lower concentrations through the A(1) receptor, whereas A(2B) and A(3) receptors have a minimal role.

Somatostatin-like immunoreactivity in the CSF of patients with dementia associated with alcoholism

Cerebrospinal fluid somatostatin-like immunoreactivity (CSF SLI) was determined for 9 patients with chronic alcohol ingestion and dementia associated with alcoholism and for 8 age-equivalent controls. The CSF SLI was significantly reduced (32%) in the alcoholics with dementia as compared to the controls. This finding is in accordance with previous observations on the relationship between reduced CSF SLI and cognitive impairment in various neuropsychiatric disorders, and extends this finding to patients with dementia associated with alcoholism.