Somatostatin-like Immunoreactivity Levels Research Articles

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.

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.

Neuropeptide abnormalities in patients with early Alzheimer disease.

Deficits in somatostatin-like immunoreactivity (SLI) and corticotropin-releasing factor immunoreactivity (CRF-IR) are well recognized as prominent neurochemical deficits in Alzheimer disease (AD). The question of whether these profound neuropeptidergic deficits found in patients with end-stage disease extend into those with much earlier disease is relatively unanswered. To determine the relation between level of SLI and CRF-IR in different cerebrocortical regions to the earliest signs of cognitive deterioration in AD. We examined SLI and CRF-IR levels in 9 neocortical brain regions of 66 elderly patients in a postmortem study of nursing home residents who had either no significant neuropathologic lesions or lesions associated only with AD. Patients were assessed by the Clinical Dementia Rating scale (CDR) to have no dementia or questionable, mild, or moderate dementia, and were compared with 15 patients with severe dementia. Both CRF-IR and SLI were significantly reduced in the cortices of patients with the most severe dementia, but only the levels of CRF-IR were reduced in those with mild (CDR = 1.0) and moderate dementia (CDR = 2.0). Levels of CRF-IR and SLI correlated significantly with CDR, but this correlation was more robust for CRF-IR and persisted even when severely cognitively impaired patients were eliminated from analysis. Although SLI and CRF-IR levels are significantly reduced in patients with severe dementia, only CRF-IR is reduced significantly in the cortices of those with mild dementia. Thus, CRF-IR can serve as a potential neurochemical marker of early dementia and possibly early AD.

Gene therapy for pancreatic carcinoma: local and distant antitumor effects after somatostatin receptor sst2 gene transfer.

Human pancreatic adenocarcinomas lose the ability to express sst2, the somatostatin receptor, which mediates the antiproliferative effect of somatostatin. Reintroducing sst2 into human pancreatic cancer cells by stable expression evokes an autocrine negative feedback loop leading to a constitutive activation of the sst2 gene and an inhibition of cell proliferation and tumorigenicity. In vivo studies have been conducted in athymic mice to investigate the antitumor bystander effects resulting from the transfer of the sst2 gene into human pancreatic cancer cell line BxPC-3. In mixing experiments, a local bystander effect was observed: mixed tumors containing a ratio of sst2-expressing cells to control cells of 25:75, 50:50, and 75:25 grew with a time delay of 31, 44, and 50 days, respectively, when compared with control tumors derived from control cells. Tumors containing 100% sst2-expressing cells remained quiescent for up to 80 days. A significant increase in apoptosis and a decrease in the Ki67 index were detected in mixed and sst2 tumor when compared with control tumors. In combined experiments, mice were separately xenografted with control cells on one flank and with sst2-expressing cells on the other flank. A distant antitumor effect was induced: growth of control tumors was delayed by 33 days, the Ki67 index decreased significantly, and apoptosis increased when compared with control tumors that grew alone. The distant bystander effect may be explained in part by a significant increase in serum somatostatin-like immunoreactivity levels resulting from the autocrine feedback loop produced by sst2-expressing cells and inducing an upregulation of the type 1 somatostatin receptor, sst1, which also mediates the antiproliferative effect of somatostatin. In conclusion, the local and distant antitumor bystander effects obtained in this experimental model suggest that sst2 gene transfer may represent a new therapy for pancreatic cancer.

Systemic anti-inflammatory effect induced by counter-irritation through a local release of somatostatin from nociceptors.

1. Neurogenic plasma extravasation evoked by topical application of 1% vv(-1) mustard oil on the skin of the acutely denervated rat hindleg (primary reaction) inhibited the development of a subsequent oil-induced plasma extravasation induced in the skin of the contralateral hindleg by 49.3+/-7.06% (n=9) and in the conjunctival mucosa due to 0.1% wv(-1) capsaicin instillation by 33.5+/-10.05% (n=6). The primary reaction also inhibited the non-neurogenic hindpaw oedema evoked by s.c. injection of 5% wv(-1) dextran into the chronically denervated hindpaw by 48.0+/-4.6% (n= 5). 2. Capsaicin injection (100 microg ml(-1) in 50 microl, s.c.) into the acutely denervated hindleg caused 56.5+/-4.0% (n=5) inhibition in the intensity of plasma extravasation elicited by 1% vv(-1) mustard oil smearing on the contralateral side. After chronic denervation, subplantar injection of 5% wv(-1) dextran elicited a non-neurogenic inflammatory response with intensive tissue oedema without causing any systemic anti-inflammatory effect. Bilateral adrenalectomy did not inhibit the mustard oil-induced anti-inflammatory effect in the contralateral hindleg. 3. Pretreating the rats with polyclonal somatostatin antiserum (0.5 ml rat(-1), i.v.) or with the somatostatin depleting agent cysteamine (280 mg kg(-1), s.c.) prevented the inhibitory action of mustard oil-induced inflammation on subsequent neurogenic plasma extravasation and strongly diminished the inhibition of non-neurogenic oedema formation evoked by dextran. 4. Exogenous somatostatin (10 microg kg(-1), i.p.) caused a 30.3+/-8.3% (n=6) inhibition of plasma extravasation caused by mustard oil smearing on the acutely denervated hindleg and this inhibitory effect was abolished by somatostatin antiserum (0.5 ml rat(-1), i.v.). The plasma level of somatostatin-like immunoreactivity (SST-LI) increased by 40.03+/-6.8% (n= 6) 10 min after topical application of 1% vv(-1) mustard oil on the acutely denervated hindpaws compared to the paraffin oil treated control group. Chronic denervation of the hindlegs or cysteamine (280 mg kg(-1), s.c.) pretreatment prevented the mustard oil-induced elevation of SST-LI in plasma. 5. It is concluded that chemical excitation of the capsaicin-sensitive sensory receptors not only induces local neurogenic plasma extravasation but also inhibits the development of a subsequent inflammatory reaction at remote sites of the body in the rat. A role for somatostatin in this systemic anti-inflammatory effect is suggested.

Neurochemical differences in the CSF between Binswanger's and Alzheimer's disease.

In 21 patients suffering from Binswanger's disease (BD) and in 53 patients suffering from Alzheimer's disease, we measured cerebrospinal fluid (CSF) concentrations of somatostatin-like immunoreactivity (SLI), high molecular weight form somatostatin (HMV-SST), somatostatin-25/28 (SST-25/28), somatostatin-14 (SST-14), Des-ala-somatostatin (Des-ala-SST), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). The patients were classified into three stages of intellectual deterioration according to the global deterioration scale (GDS). Levels of SLI were significantly decreased in BD in general and in SDAT patients with severe dementia (GDS 7), compared to a control group (BD overall 19.7 +/- 11.6 fmol/ml, SDAT 18.6 +/- 7.9 vs. 30.5 +/- 8.6 fmol/ml in controls, p < 0.01 for both). In SDAT patients, SLI levels correlated with dementia scores (r = -0.65, p < 0.05), but not in BD. HVA levels were decreased significantly in SDAT and BD patients with severe dementia (SDAT 273.5 +/- 138.7, BD 224.3 +/- 69.9 vs. 364.9 +/- 103.8 nmol/ml, p < 0.01 in controls, p < 0.05 for both). In BD patients with light dementia (GDS 2-4), HVA levels were significantly elevated (p < 0.05). In BD, HVA levels correlated with dementia (r = -0.59, p < 0.01). 5-HIAA was significantly elevated in BD patients with light dementia (p < 0.05). Qualitative and quantitative changes in the molecular forms of SLI are compatible with a dysregulated posttranslational processing SDAT and BD. We also observed significant correlations between SLI, 5-HIAA and HVA in BD indicating a neurochemical heterogeneous and generalized process affecting several transmitter systems and functions. In summary, our study shows that despite their quite different neuropathology, SDAT and BD do not differ fundamentally in their neurochemical profile.

Somatostatin, its Molecular Forms and Monoaminergic Transmitter Metabolites in Binswanger's Disease. Neurochemical-Neuropathological Considerations

Cerebrospinal fluid (CSF) concentrations of somatostatin-like immunoreactivity (SLI), high molecular weight form somatostatin (HMV-SST), somatostatin-25/28 (SST-25/28), somatostatin–14 (SST-14), Des-ala-somatostatin (Des-ala-SST), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5–HIAA) were measured in 21 patients with Binswanger's dementia (BD). Patients were classed into three stages of intellectual deterioration according to the Global de-terioration scale (GDS). Levels of SLI were significantly decreased in patients suffering from BD, compared to a control group (19.7 ± 11.6 fmol/ml vs. 30.5 ± 8.6 fmol/ml, P< 0.01). There was no correlation with dementia scores ( r= 0.34, P= 0.51). The observed qualitative and quantitative changes in the molecular pattern of SLI suggest the occurrence of a dysregulated posttranslational processing in patients with BD. Whereas 5-HIAA levels were not significantly changed in patients with BD, HVA was significantly increased in mild to moderate dementia (GDS 2-4) and significantly decreased in severe cases (GDS 7) (224.3 ± 69.9 nmol/ml vs. 364.9 ± 103.8 nmol/ml, P< 0.01); this correlated with dementia scores ( r= −0.59, P< 0.01). The existence of significant correlations between SLI, 5-HIAA and HVA in BD point to a heterogeneous and generalized neurochemical process affecting several transmitter systems and functions.

The benzodiazepine antagonist CGS 8216 prevents hyperammonemia-induced somatostatin receptor reduction in the brain.

Previous results from our group showed that hyperammonemia decreases the number of somatostatin (SS) receptors and that benzodiazepine receptors might regulate the number of SS receptors in rat brain. These findings together with the supersensitivity of benzodiazepine receptors in the hyperammonemic rat brain suggest that benzodiazepine receptors might mediate the effect of hyperammonemia on SS receptors. To assess this hypothesis we tested whether 2-phenylpyrazolo[3,4-c]-quinolin-3(5H)-one (CGS 8216), a benzodiazepine antagonist, prevented the effect of ammonium acetate on rat brain SS receptors. Administration of ammonium acetate (5 mmol/kg, i.p.) for 7 days did not affect the levels of somatostatin-like immunoreactivity but decreased the number of SS receptors in synaptosomes from the frontoparietal cortex and hippocampus without affecting their apparent affinity. This decrease could be blocked by the concomitant administration of CGS 8216 (10 mg/kg, i.p.). The benzodiazepine antagonist alone had no observable effect on the somatostatinergic system. These results suggested that the effect of hyperammonemia on SS receptors could be mediated, at least in part, through the benzodiazepine receptors.

Exogenous histamine increases the somatostatin receptor/effector system in the rat frontoparietal cortex

The present study examined the effects of histamine on somatostatin-like immunoreactivity levels, binding of 125I-[Tyr 11]somatostatin to its specific receptors, somatostatin inhibition of basal and forskolin-stimulated adenylyl cyclase activity and inhibitory guanine-nucleotide binding protein (G i) function in the rat frontoparietal cortex. An intracerebroventricular (i.c.v.) dose of 10 μg or 1 μg of histamine induced an increase in the number of specific 125I-[Tyr 11]somatostatin receptors (590 ± 22 vs 358 ± 12 fmol/mg protein, P < 0.001 and 455 ± 20 vs 342 ± 21 fmol/mg protein, P < 0.01, respectively) together with a decrease in their apparent affinity (0.76 ± 0.04 vs 0.39 ± 0.02 nM, P < 0.001 and 0.60 ± 0.03 vs 0.39 ± 0.05 nM, P < 0.01, respectively) in rat frontoparietal cortex membranes. This increase in tracer binding was not due to a direct effect of histamine on the somatostatin receptors since no change in binding was produced when histamine was added directly to the incubation medium. No significant differences were seen for either the basal or forskolin-stimulated adenylyl cyclase activity in frontoparietal cortex membranes of histamine-treated rats as compared with the control group. In rats treated with 10 μg of histamine, however, somatostatin caused a significantly greater inhibition of basal and forskolin-stimulated adenylyl cyclase activity as compared to the control group (33 ± 4% vs 19 ± 1% inhibition, P < 0.05 and 31 ± 1% vs 21 ± 3% inhibition, P < 0.05, respectively). The functional activity of the G i protein, as measured by the capacity of the stable GTP analogue 5′guanylylimidodiphosphate [Gpp(NH)p] to inhibit forskolin-stimulated adenylyl cyclase activity, was not altered by 10 μg of histamine in frontoparietal cortex membranes. Therefore, the observed increase in somatostatin inhibition of adenylyl cyclase activity in the frontoparietal cortex from rats treated with this histamine dose may be caused by the increase in the number of somatostatin receptors. To determine whether the above-mentioned changes are related to histamine binding to its specific receptor sites H 1 and H 2, one group of rats were pretreated with the histamine H 1 H 2 receptor antagonists mepyramine and cimetidine, respectively, which were administered simultaneously. This pretreatment prevented the histamine-induced changes in the somatostatin receptor/effector system in the frontoparietal cortex. In conclusion, these results suggest that the somatostatinergic system present in the frontoparietal cortex can be regulated by histamine and that this regulation may be implicated in some of the behavioural effects of histamine and somatostatin.

In Vivo and in Vitro Effects of Adenosine-5???-0-(2-thiodiphosphate) on Pancreatic Hormones in Dogs

Adenosine-5'-O-(2-thiodiphosphate) (ADP beta S), a P2y purinergic agonist, has been shown to be a potent insulin secretagogue on the isolated rat pancreas. In the present work the effects of ADP beta S on insulin somatostatin, and glucagon secretions were investigated in dogs. In vivo, in anesthetized fasted dogs, i.v. ADP beta S (0.1 mg kg-1) induced an immediate increase in insulin and somatostatin-like immunoreactivity (SLI) but not in glucagon pancreaticoduodenal outputs. In conscious fasted dogs, i.v. ADP beta S (0.1 mg kg-1) produced an immediate and transient augmentation in plasma insulin levels but not in plasma SLI and glucagon levels. In vitro, the effects of ADP beta S were investigated on the isolated uncinate process of dog pancreas, from normal and alloxan-diabetic animals. In normal uncinate process, in presence of 8.3 mM glucose, ADP beta S (1 microM) stimulated insulin and SLI releases but not glucagon release. On uncinate process from diabetic animals, ADP beta S (1 microM) retained its stimulating effects but the responses were impaired as compared with normal dogs: Insulin response was drastically diminished and SLI response strongly enhanced. In conclusion, ADP beta S is a potent insulin secretory agent in dog. This P2y purinoceptor agonist, which exerts a direct stimulatory effect on pancreatic SLI, is interestingly devoid of direct glucagonotropic properties.

Reduced cerebral cortical but elevated striatal concentration of somatostatin-like immunoreactivity in dominantly inherited olivopontocerebellar atrophy.

Somatostatin-like immunoreactivity (SLI) was measured in the brains of nine patients with dominantly inherited olivopontocerebellar atrophy (OPCA), who all had a marked deficit of the cholinergic marker choline-acetyltransferase (ChAT) in the cerebral cortex and striatum. Mean concentrations of SLI in OPCA were significantly reduced by 42-58% in parietal and occipital cortices and frontal cortical eye fields, but were normal in other cortical areas, including two subdivisions of the temporal cortex which show marked depletions of both SLI and ChAT in Alzheimer's disease. This dissociation of SLI and ChAT indicates that a cortical cholinergic deficit does not invariably lead to reduction of somatostatin. In the caudate nucleus, the region of OPCA brain having the most severe ChAT deficit (-81%), SLI levels were significantly elevated by 46% and were negatively and significantly correlated with ChAT activities (r = -0.66). The SLI alterations could be due to abnormal somatostatin metabolism or release, or an increased number of somatostatin-containing neurons and could contribute to the brain dysfunction of OPCA.

Effect of ammonium acetate on the somatostatinergic system in the rat frontoparietal cortex

Short (90 min)-, mid (5 days)-, and long-term (15 days) ammonium acetate (5 mmol/kg IP) administration decreased the number of specific [ 125I][Tyr 11]somatostatin receptors in synaptosomes from the frontoparietal cortex without changing the affinity constant. Administration of ammonium acetate did no affect the levels of somatostatin-like immunoreactivity in the frontoparietal cortex. The administration of a single dose of N- carbamyl - l-glutamate (1 mmol/kg) plus l-arginine (1 mmol/kg) 1 h before the last administration of ammonium acetate totally blocked the inhibitory effects of the latter on somatostatin receptor number in the frontoparietal cortex synaptosomes. N- Carbamyl - l-glutamate plus l-arginine alone had no observable effect on the somatostatinergic system. The decrease in the number of somatostain receptors induced by ammonium acetate might reflect decreased target cell sensitivity to somatostatin, a phenomenon that could contribute to the depressed neuronal excitability induced by ammonia in the rat frontoparietal cortex.

The effect of diazepam and the benzodiazepine antagonist CGS 8216 on the somatostatinergic neuronal system

The effects of the benzodiazepines and somatostatin (SS) on learning and memory are the opposite of each other. To investigate a possible relationship between these two components, the effects of the administration over time of diazepam and of a benzodiazepine antagonist, 2-phenylpyrazolo [3,4-c]-quinolin-3(5H)-one (CGS 8216), on the levels of somatostatin-like immunoreactivity (SSLI) and on the binding of [ 125I]Tyr 11-somatostatin were studied in the hippocampus of the Wistar rat. Diazepam (5 mg/kg/day, i.p.) and CGS 8216 (20 mg/kg/day, i.p.) did not affect SSLI in the hippocampus, at the three times studied (3, 7 or 14 days). Administration of diazepam for 3 or 7 days decreased the number of somatostatin receptors in synaptosomes from the hippocampus, without influencing their apparent affinity. This decrease could be blocked by concomitant administration of CGS 8216, whereas CGS 8216 alone had no observable effect. After 2 weeks of daily injections of diazepam the levels of binding of somatostatin in the hippocampus returned to control values, coinciding with the tolerance that develops to chronically-administered benzodiazepine agonists. These results suggest that somatostatin receptors might be regulated by benzodiazepine receptors and perhaps may also play a role in some of the behavioural effects of the benzodiazepines.

Role of somatostatin in glucose regulation during endotoxicosis in the rat.

This study assessed the role of somatostatin in regulating glucose homeostasis during endotoxicosis in the rat. Plasma levels of somatostatin, glucose, lactate, insulin, and glucagon were measured in control and endotoxin-treated rats. Cysteamine was used to block endogenous somatostatin release before endotoxin treatment. Early during the course of endotoxicosis, plasma levels of somatostatin-like immunoreactivity (SLI) were significantly elevated along with glucose, lactate, insulin, and glucagon. Pretreatment of endotoxic rats with cysteamine virtually blocked the elevated SLI levels and prevented the early appearance of hyperglycemia. Endotoxin-induced increases in lactic acid and glucagon levels were attenuated by cysteamine pretreatment, but elevated insulin levels were not appreciably altered. Elevated somatostatin levels appeared to support the occurrence of the early hyperglycemia and prevent the development of late hypoglycemia during endotoxicosis by sustaining elevated glucagon levels and thus facilitating the maintenance of glucose levels. The results suggest that somatostatin plays a significant role in the glucoregulatory response to endotoxicosis. Endotoxicosis may alter the relative "physiological" ability of somatostatin to inhibit the secretion of insulin and glucagon.

Effect of prenatal dopamine receptor blocking on somatostatin receptor binding in the developing rat brain

To date, the possible functional interaction between the dopaminergic and the somatostatinergic system during the development of the brain is unknown. This study examines whether blockage of brain dopamine receptors during fetal life might influence postnatal somatostatin (SS) receptor development. Pregnant Sprague-Dawley rats were injected intraperitoneally with either haloperidol (2.5 mg/kg/day), which blocks dopaminergic receptors, or saline. The injections were given for 16 days, commencing on the 4th or 5th day after conception (as counted from the appearance of spermatozoa in daily vaginal smear). The administration of haloperidol during gestation did not affect the levels of somatostatin-like immunoreactivity (SLI) in the two brain areas at any of the times studied. However, this treatment resulted in a decrease in the total number of receptors for 125I-Tyr 11-SS in frontoparietal cortex and hippocampal plasma membranes in the 14-day-old offspring but not at 21, 35, or 60 days after birth. No significant differences in the apparent SS binding affinity values were seen after fetal exposure to haloperidol. These results suggest that the development of SS receptors in rat frontoparietal cortex and hippocampus can be transitorily delayed by fetal blockage of dopamine receptors.

Somatostatin in the cerebrospinal fluid of schizophrenic patients before and after neuroleptic drug treatment

A radioimmunoassay procedure was used to determine levels of somatostatin-like immunoreactivity in cerebrospinal fluid obtained from 9 schizophrenic patients, 7 patients with other psychiatric disorders, and 10 nonpsychiatric surgical controls. There were no significant differences in mean somatostatin baseline levels between the schizophrenic, and surgical patients. The concentrtion remained almost unaltered after 4 weeks of zuclopenthixol treatment in the schizophrenia group and following various neuroleptic, antidepressant, and anxiolyic medications in the nonschizophrenic patients despite a significant decrease of over psychopathology assessed by the Brief Psychiatric Rating Scale.

Somatostatin binding reduced by ammonium acetate in the rat hippocampus can be reversed by treatment with N-carbamyl-L-glutamate plus L-arginine.

The effects of short-term (90 min), mid-term (5 days), and long-term (15 days) administration of ammonium acetate (5 mmol/Kg day i.p.) on the somatostatinergic neurotransmitter system of the rat hippocampus have been studied. Scatchard analysis of the binding of 125I-Tyr11-somatostatin to hippocampal dissociated cells indicated that administration of ammonium acetate at the times studied were associated with a decrease in the number of somatostatin receptors in this brain area, whereas the affinity of the same receptors remained unchanged. Administration of ammonium acetate did not affect the levels of somatostatin-like immunoreactivity in the hippocampus. Treatment with N-carbamyl-L-glutamate (1 mmol/Kg, i.p.) plus L-arginine (1 mmol/kg), which lead to the conversion of ammonia into urea, prevented the ammonium acetate-induced changes in somatostatin binding in this brain area. N-carbamyl-L-glutamate plus L-arginine alone had no observable effect on the somatostatinergic system. The decrease in the number of somatostatin receptors induced by ammonium acetate might reflect a decreased sensitivity of the target cells to somatostatin, a phenomenon that could contribute to the depressed neuronal excitability induced by ammonia in the rat hippocampus.

Low levels of somatostatin-like immunoreactivity in neocortex resected from presumed seizure foci in epileptic patients

The concentration of somatostatin-like immunoreactivity (SS-LI) was determined by radioimmunoassay in neocortical tissue resected from 20 patients with pharmacologically intractable complex partial seizures. Most resections included either the anterior temporal pole neocortex (15 cases) or cingulate gyrus neocortex (3 cases). The concentration of SS-LI was lowest in cortical tissue immediately adjacent to cortical tumors. Preoperative electrical recordings suggested that this tissue was the seizure focus. In vitro recordings showed that this tissue also exhibited abnormal hyperexcitable synaptic responses. Higher levels of SS-LI, similar to normal values previously reported in human cortex, were present in non-focal temporal neocortical tissue (resected from patients in whom the seizure focus was in the ipsilateral hippocampus) in which no hyperexcitable synaptic activity was present in vitro. The functional loss of inhibitory transmitters suggested by the low SS-LI levels might provide a theoretical basis for the hyperexcitability observed in vivo and in vitro.

Maternal ethanol ingestion and somatostatin level and binding in developing rat brain

The effect of maternal ethanol ingestion on 125I-labeled [Tyr11]somatostatin (SS) binding and somatostatin-like immunoreactivity (SLI) in the rat frontoparietal cortex and hippocampus of developing offspring was explored. Female Sprague-Dawley rats were given ethanol in the drinking water before pregnancy, during gestation, and while nursing, whereas controls received a standard diet and fresh water ad libitum. In the ethanol group, food intake decreased as ethanol consumption augmented, with the ethanol calories comprising greater than 30% of the total energy intake during pregnancy. Total energy intake was similar for the ethanol group and normal controls. Maternal alcohol ingestion is associated with an enhanced SLI level in the frontoparietal cortex and hippocampus on the day of birth. This study provided evidence of a selective decrease in SS receptor binding in frontoparietal cortex but not in hippocampus in the 0- to 10-day-old offspring of the ethanol-fed rats. The SS receptor number increased from day 0 to 10 in both control and ethanol groups. However, the affinity appeared to decrease significantly in the ethanol group during this period. At day 30, no differences were found between offspring of control and ethanol-treated rats in any of the parameters. These results suggest that the development of SS receptors in the rat frontoparietal cortex can be transitorily delayed by maternal ethanol ingestion.

Effect of maternal exposure to nicotine in the rat on level and binding of somatostatin in brain of developing offspring

The effect of maternal exposure to nicotine on the level of somatostatin and specific binding in frontoparietal cortex and hippocampus of developing offspring was investigated. Sprague-Dawley rats were injected subcutaneously, throughout the pregnancy and the nursing period, with either: 3 mg kg nicotine base or saline vehicle. In the offspring of control rats, the level of somatostatin-like immuno-reactivity peaked at day 10 in the frontoparietal cortex, whereas the level of immunoreactivity in the hippocampus was the highest on day 30. Maternal exposure to nicotine caused enhanced levels of immunoreactivity in the frontoparietal cortex, on the day of birth and in the hippocampus, up to day 10. The maximum specific binding of somatostatin to the receptors in membranes from the frontoparietal cortex, peaked at 10 days of age in the offspring of control rats. The number of somatostatin receptors in cortical (but not in hippocampal) membranes was significantly decreased in the 0- to 10-day-old offspring of the nicotine-treated rats. Despite transient alterations in the number of somatostatin receptors, the affinity of the sites for somatostatin was consistently unchanged. The levels of somatostatin-like immunoreactivity and the number of somatostatin receptors in the frontoparietal cortex and hippocampus was comparable in the 30-day-old offspring of the control and nicotine-treated rats.