Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cysteamine and propionitrile cause severe duodenal ulcers with perforation within 24-48 h after a single injection in rats. These animal models were used to gain insight into the early, preulcerogenic biochemical changes in the duodenal mucosa. The results indicate that a single sc injection of cysteamine and propionitrile induced dose- and time-dependent decreases in the activity of phosphoprotein phosphatase (PPPase) in homogenate and particulate fractions of rat duodenal mucosa. The decrease in enzyme activity was detectable 4 h after the injection of the ulcerogens, it was maximal at 12 h, and hardly detectable at 24 h. No effect on the enzyme activity was found under in vitro conditions. PPPase activity in the liver was not influenced by either cysteamine or propionitrile. Furthermore, the toxic but nonulcerogenic derivative of cysteamine ethanolamine had no effect on PPPase in the duodenum. Thus, the effect of the duodenal ulcerogens on PPPase activity was indirect and organ specific, related only to the target organ (i.e., duodenal mucosa). The effect of the drugs was also selective at the level of mucosal cells: both duodenal ulcerogens depleted protein and alkaline phosphatase but not lysosomal acid phosphatase. The decrease of PPPase activity could be a general property of the duodenal ulcerogens since it is independent of their effect on endogenous somatostatin.
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PMID:The influence of cysteamine and propionitrile on duodenal phosphoprotein phosphatase in rats. 289 91

Intracerebroventricular (i.c.v.) administration of somatostatin-28 (SS-28) (30 ng-1 micrograms) resulted in a dose-dependent elevation of plasma concentrations of vasopressin. Continuous i.c.v. infusion of SS-28 produced a depletion of vasopressin-like immunoactivity within the paraventricular and supraoptic of the hypothalamus as determined by immunocytochemistry. To evaluate the role of endogenous brain somatostatin in the regulation of vasopressin secretion, animals were treated with cysteamine. Cysteamine (90 mg/kg) treatment given s.c. produced a 50% depletion of endogenous brain somatostatin-like peptide concentrations. Pretreatment of animals with cysteamine attenuated hemorrhage-induced elevation of plasma vasopressin levels. The elevation of plasma vasopressin concentrations following the i.v. administration of hypertonic saline or the i.c.v. administration of angiotensin-II were not altered by cysteamine treatment. These results are consistent with the conclusion that an endogenous brain somatostatin may be involved in the physiologic regulation of vasopressin secretion following hemorrhage.
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PMID:Role of somatostatin in the regulation of vasopressin secretion. 290 49

Administration of cysteamine (beta-mercaptoethylamine; 2-aminoethanethiol) to rats has been shown to decrease the levels of somatostatin-like immunoreactivity (SLI) in the gastrointestinal tract and pancreas but its mode of action is unclear. In the current study the effect of cysteamine on gastrointestinal and pancreatic SLI has been studied using two antisera with different regional specificities. In addition, the in vitro effect of cysteamine on SS-14 and SS-28 has been studied by high-performance liquid chromatography (HPLC). Characterization of the two antisera (AS 26.3.2 and AS 1001) with a range of analogs of SS-14 revealed that both were directed against the midportion of the molecule but that AS 1001 was also sensitive to changes at the N- and C-termini. Tissue extracts from cysteamine-treated rats measured with AS 26.3.2 showed no significant change for the stomach, jejunum or pancreas but duodenal levels were reduced. With AS 1001 SLI levels were reduced in all tissues. Gel permeation chromatography of stomach extracts measured with AS 1001 showed a reduction in both SS-14 and SS-28. With AS 26.3.2 an increase in SLI eluting prior to the SS-14 peak occurred explaining why no significant reduction in total SLI was detected. With duodenal extracts the elution profiles with AS 1001 reflected the large reduction in total SLI whereas with AS 26.3.2 a smaller reduction occurred. Both SS-14 and SS-28 were reduced. HPLC analysis of SS-14 and SS-28 following incubation with cysteamine in vitro showed a time-dependent decrease in both somatostatin species with absorbance at 280 nm was measured. New peptide peaks which developed were not all detectable by radioimmunoassay with either antibody. The results suggest that cysteamine causes a change in the structure of somatostatin which probably first involves a reduction of the disulphide bridge and then the N- and C-terminal regions of the molecule thus making it unmeasurable by antisera sensitive to changes in these regions.
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PMID:Cysteamine-induced reduction in gastrointestinal somatostatin: evidence for a region-specific loss in immunoreactivity. 290 Nov 34

The involvement of somatostatin in the organization of cognitive functions was studied. We assessed changes in learning and memory processes by studying the effects of cysteamine, a compound that decreases somatostatin-like immunoreactivity in the brain, somatostatin and the potent somatostatin analogue, SMS 201-995, on active avoidance behaviour, assessed with a shuttle box apparatus, or on passive avoidance behaviour. Cysteamine induced a loss of the conditioned active avoidance response acquired after 3 weeks of daily trials. The effect was observed 2 h (-29%) and 4 h (-51%) after cysteamine treatment (300 mg/kg s.c.) and disappeared after 24 h. Intracerebroventricular administration of somatostatin or SMS 201-995 to cysteamine-treated rats significantly reversed the cysteamine effects on the conditioned avoidance responses. Similar results were obtained on passive avoidance behaviour. We also investigated the effect of cysteamine treatment on brain somatostatin-sensitive adenylate cyclase. We observed that adenylate cyclase activity in the frontal cortex of cysteamine-pretreated animals was more sensitive to inhibition by the SRIF analogue, SMS 201-995, than it was in control animals. This effect was observed at concentrations of SMS 201-995 that were ineffective in control tissue. These results show that disruption of somatostatinergic transmission affects cognitive functions of rats.
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PMID:Somatostatin and SMS 201-995 reverse the impairment of cognitive functions induced by cysteamine depletion of brain somatostatin. 290 59

Cysteamine, when given in vivo to rabbits, depleted immunoreactive somatostatin in rabbit gastric fundic mucosa. Depletion of immunoreactive somatostatin was associated with both an increase in the number and a decrease in the affinity of the low-affinity somatostatin binding sites. The in vitro incubation of cysteamine (0.1 mM) with the cytosolic fraction did not result in any modification of somatostatin binding. These results suggest that a decrease in the endogenous immunoreactive somatostatin might lead to up-regulation of somatostatin binding sites in the gastric fundic mucosa.
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PMID:Modulation of somatostatin binding sites in cytosol of rabbit gastric fundic mucosa by cysteamine administration. 302 1

The effect of the somatostatin depleting substance, cysteamine (100 mg/kg, i.p.), on cortical and amygdaloid kindled seizures was investigated. Cysteamine was tested after the establishment of amygdaloid kindling (AM group) and at two different developmental stages of cortical kindling, namely 'focal-cortical' (FC group) and 'cortico-generalized' seizures (CG group). In control, non-kindled, sham operated animals, cysteamine did not induce any spike activity or myoclonus. However, in all kindled groups clustered spike bursting appeared in the cortex within 5-15 min of the injection. The kindled bursting appeared in the cortex within 5-15 min of the injection. The kindled rats exhibited myoclonic jerks at 10 to 30 min after cysteamine injection, which coincided with the cortical spikes, and continued for about 40 min. In contrast, relatively small amounts of spiking were observed in the amygdala and this did not correlate with the myoclonus. At 4 h after cysteamine injection, the motor seizure and afterdischarge durations of the kindled seizure were prolonged in all kindled groups compared with preinjection levels. However, 24 h later the motor seizure duration and the afterdischarge duration were markedly reduced from the preinjection level in the AM and the CG groups and the tonic seizure component was suppressed in the FC group. This inhibitory effect on seizure activity lasted several days and gradually disappeared. These modifying effects of cysteamine were more marked in cortical kindled, than in amygdaloid kindled animals. The results suggest that the cortex is more sensitive to the effect of cysteamine on kindled seizures involves two phases. The first of these effect of cysteamine on kindled seizures involves two phases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myoclonus inducing and seizure modifying effect of cysteamine on cortical and amygdaloid kindled rats. 314 96

Thioredoxin and thioredoxin reductase (NADPH-oxidized thioredoxin oxidoreductase, E.C. 1.6.4.5) have been proposed to be involved in several thiol-dependent reduction-oxidation reactions in cells. Both proteins have been immunohistochemically demonstrated in the periphery of the cytoplasm and in cytoplasmic granules of acinar and islet cells in mouse pancreas. In animals fed ad libitum, the staining for thioredoxin was more intense in the exocrine acinar cells than in the islet cells, whereas that for thioredoxin reductase was more intense in the endocrine than in the exocrine pancreas. In the islets of fed mice all endocrine cell types showed about the same staining intensity for thioredoxin, while thioredoxin reductase was greatly enriched in the somatostatin-containing D cells. Starvation overnight caused an increased staining for both proteins in the acinar cells as well as in the islets. Under conditions of starvation, thioredoxin reductase, in contrast to thioredoxin, appeared to increase preferentially in the islet B cells, as compared with the D cells. Cysteamine treatment reduced the staining for somatostatin and for thioredoxin reductase in the D cells without any obvious effect on the other pancreatic cells. The results are compatible with a role for thioredoxin and thioredoxin reductase in secretion.
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PMID:Immunohistochemical localization of thioredoxin and thioredoxin reductase in mouse exocrine and endocrine pancreas. 352 49

The effects of a wide range of doses of systemically administered cysteamine were studied on locomotor behavior, passive avoidance memory, cortical and cerebrospinal fluid somatostatin-like immunoactivity and cortical levels of dopamine and norepinephrine. High doses of cysteamine (200 and 250 mg/kg s.c.) led to sustained locomotor activation. Doses of 150 mg/kg and above resulted in head and neck tremor and increased defecation. When cysteamine was administered immediately following the acquisition of a passive avoidance response, doses of 50 mg/kg and above resulted in significant attenuation of passive avoidance retention test performance. Cysteamine in doses of 50 mg/kg and above depleted cortical somatostatin-like immunoactivity by approximately 50%. The depletion of cortical somatostatin-like immunoactivity was accompanied by a rapid rise in somatostatin-like immunoactivity in cerebrospinal fluid. In addition to the depletion of somatostatin-like immunoactivity, high doses of cysteamine (150 mg/kg and above) produced changes in cortical levels of norepinephrine and dopamine, reminiscent of dopamine-beta-hydroxylase inhibition. The results of this series of experiments suggest that somatostatin, in addition to its effects on hormonal regulation, may play an important role in behavior and passive avoidance learning and memory. It is possible that the amnesia produced by cysteamine may have been due to the release of somatostatin into CSF from tissue stores, rather than somatostatin depletion per se. It is also possible that the catecholaminergic effects of high doses of cysteamine contribute to the behavioral deficits observed.
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PMID:Cysteamine-induced depletion of central somatostatin-like immunoactivity: effects on behavior, learning, memory and brain neurochemistry. 382 20

Cysteamine (beta-mercaptoethylamine, MEA) is a naturally occurring sulfhydryl compound that depletes pituitary PRL, causes a reduction in brain and gut somatostatin (SRIF), and suppresses norepinephrine (NE) and epinephrine (EPI) synthesis by inhibition of dopamine-beta-hydroxylase (DBH). SRIF inhibits GH and TSH secretion, whereas, NE and EPI facilitate their release. The objectives of this investigation were to: (1) determine the dose-response and time course of DBH inhibition by MEA in vivo and in vitro, and correlate these findings with MEA tissue levels and (2) assess the function of SRIF and NE/EPI in regulation of episodic GH and TSH secretion using MEA. Animals were administered MEA (75-300 mg/kg, s.c.) and hypothalamic levels of dopamine (DA), NE, EPI, serotonin (5-HT) and MEA were measured by high-performance liquid chromatography (HPLC) and electrochemical detection. DBH activity was measured in vitro after exposure to MEA +/- N-ethylmaleimide (NEMI). Chronically cannulated rats were administered MEA (100 or 300 mg/Kg) and serial blood samples were removed in undisturbed animals, and after 30 min swimming stress. Cannulated rats with bilateral lesions of the ventromedial/arcuate nuclei (VMN/ARC) were administered MEA (150 mg/kg). MEA caused a dose-related decrease in NE/EPI nd in increase in DA at doses greater than or equal to 150 mg/kg. Tissue MEA was highest at 4 h (679 +/- 64 pM/mg tissue), but still measureable after 24 h. MEA inhibited DBH in vitro (95% inhibition at 10(-3) M); NEMI blocked inhibition. Stress-induced GH supression and corticosterone release were partially blocked by a low dose of MEA (100 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cysteamine effects on monoamines, dopamine-beta-hydroxylase and the hypothalamic-pituitary axis. 408 89

Cysteamine given subcutaneously to rats decreases brain concentrations of somatostatin-like immunoactivity (SLI) but does not affect vasopressin-like immunoactivity as determined by radioimmunoassay and immunocytochemistry. Since somatostatin-related peptides act within the central nervous system (CNS) to increase body temperature and decrease adrenal epinephrine secretion, changes in these parameters were assessed following cysteamine administration. Cysteamine administration lowers oxygen consumption and body temperature, and elevates plasma concentrations of epinephrine, glucose, insulin and glucagon. The lowering of body temperature and elevation of plasma epinephrine is prevented by CNS administration of the CNS-selective somatostatin analog desAA1,2,4,5,12,13[D-Trp8 ))somatostatin. The CNS actions of somatostatin-related peptides are opposite to the effects of cysteamine. The observations are consistent with the possibility that brain somatostatin-related peptides are involved in regulation of body temperature and adrenal epinephrine secretion.
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PMID:Biological effects of cysteamine: relationship to somatostatin depletion. 613 1


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