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

A review of biochemical findings is presented which support the idea that Alzheimer's disease represents a condition for which tetrahydroaminoacridine (tacrine) may have a beneficial effect. There is evidence that clinical and histopathologic hallmarks of the disease relate to cholinergic and serotonergic dysfunction, with less obvious abnormalities in other neurotransmitters (aspartate, dopamine, gamma-aminobutyrate, glutamate, noradrenaline and somatostatin). Clinically relevant concentrations of tacrine may ameliorate the above presynaptic deficits without producing harmful (neurotoxic) effects of aspartate and glutamate. The disease seems to be associated with an early and clinically relevant degeneration of some neurons with cortical perikarya that release these amino acid transmitters. Studies are now required on the effect of tacrine on postulated harmful peptide-bond hydrolase activity within and around such cells.
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PMID:Tacrine, a drug with therapeutic potential for dementia: post-mortem biochemical evidence. 257 13

Concentrations of preprosomatostatin-mRNA and preprocholecystokinin-mRNA were determined by Northern blot analysis in rats 2, 10, and 30 days after strong seizures induced by a single intraperitoneal injection of kainic acid. At all time intervals examined, levels of preprosomatostatin-mRNA were increased in the frontal cortex; so were levels of preprocholecystokinin-mRNA in the striatum. Transient increases, i.e., 2 days after kainic acid, of preprocholecystokinin-mRNA were observed in the frontal cortex and the substantia nigra. Preprocholecystokinin-mRNA was reduced in the hippocampus 2 and 10 days after kainic acid. Both preprosomatostatin- and preprocholecystokinin-mRNA levels showed a tendency to be reduced in the amygdala/pyriform cortex at all three time intervals. The increases in mRNA levels suggest enhanced rates of synthesis of the respective neuropeptides subsequent to kainic acid-induced seizures. They may also reflect a prolonged increase in the activity of the respective peptide-containing neurons. This is of special interest in the frontal cortex, since in this area both neuropeptides are found in interneurons and are widely colocalized with gamma-aminobutyric acid.
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PMID:Concentrations of mRNAs encoding for preprosomatostatin and preprocholecystokinin are increased after kainic acid-induced seizures. 257 87

To stimulate peripheral gamma-aminobutyric acid (GABA) receptors, GABA, which does not cross the blood-brain barrier, was administered to dogs with vagally innervated gastric fistulas at intravenous doses of 0, 0.66, 2, 6, 18, and 54 micrograms.kg-1.min-1. Mean gastric acid output increased from zero basally to 3.0 +/- 1.4 mmol/h during infusion of 54 micrograms.kg-1.min-1 GABA. Plasma somatostatin-like immunoreactivity decreased significantly below basal levels during infusion of 54 micrograms.kg-1.min-1 GABA (P less than 0.05). To stimulate central nervous system GABA receptors as well as peripheral GABA receptors, progabide, a GABA-receptor agonist, which readily crosses the blood-brain barrier, was injected intravenously. Mean acid output was 3.5 +/- 1.3 mmol/h after 20 mg/kg progabide and 0.6 +/- 0.5 mmol/h after its vehicle (P less than 0.05). Basal serum gastrin concentration increased significantly after progabide injection. Acid output during insulin-induced hypoglycemia was inhibited 59% by 30 mg/kg intravenous progabide. Progabide infusion also diminished or abolished circulating gastrin, somatostatin, and pancreatic polypeptide responses during insulin-induced hypoglycemia (P less than 0.05). Further studies were performed in dogs with a gastric fistula and a vagally denervated Heidenhain pouch to confirm that GABA-receptor stimulation affects acid secretion via peripheral pathways. Intravenous injection of baclofen (0.5 mg/kg), a GABAB-receptor agonist, increased acid secretion significantly from the gastric fistula and the Heidenhain pouch. These studies suggest that GABA may play a role in regulating gastric acid secretion and gastrointestinal and pancreatic endocrine function by both central and peripheral mechanisms.
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PMID:Effect of GABA on basal and vagally mediated gastric acid secretion and hormone release in dogs. 283 63

Prolactin release-inhibiting factor (PIF) extracted from 1200 sheep stalk-median eminences was purified by gel filtration on a Sephadex G-25 column (4.5 X 150 cm). PIF activity was determined by measuring the inhibition of prolactin release from dispersed anterior pituitary cells of adult male or estrogen-primed, ovariectomized rats. Using this system, PIF was detected in tube fractions 122-127 (volume = 20 ml/tube). These fractions also contained LHRH and somatostatin; however, these peptides had no prolactin-inhibiting activity in the quantities present. No dopamine or gamma-aminobutyric acid (GABA) was detected in the active fractions by radioenzymatic assay and fluorophotoenzymatic assay, respectively. Furthermore, receptor blockers for dopamine or GABA did not interfere with the PIF activity. These findings indicate that the PIF activity cannot be attributed to either dopamine or GABA, both of which are known to inhibit prolactin release, and provide evidence for the presence of a non-dopaminergic and non-GABAergic PIF within the hypothalamus.
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PMID:Purification of a non-dopaminergic and non-GABAergic prolactin release-inhibiting factor (PIF) in sheep stalk-median eminence. 285 51

Specific somatostatin (SRIH) receptors on human pituitary adenoma cell membranes were characterized using [125I]Tyr11-SRIH as the radioligand. Specific binding of [125I] Tyr11-SRIH to adenoma cell membranes reached a steady state within 30 min at 25 C, and semilogarithmic analysis of the data revealed that the rate of the binding was linear at 25 C with a t1/2 of 13.2 min. Specific binding increased linearly with 5-160 micrograms plasma membrane protein. SRIH-14 and SRIH-28 inhibited [125I]Tyr11-SRIH binding to adenoma cell membranes with ID50S of 0.32 and 0.50 nM, respectively, while secretin, glucagon, gastrin, cholecystokinin-8, bombesin, TRH, LHRH, human GH-releasing factor-(1-44)-NH2, D-Ala2-met-enkephalin, gamma-aminobutyric acid and taurine did not significantly inhibit binding. All of 13 GH-secreting adenomas investigated had specific and high affinity SRIH receptors, with a dissociation constant (Kd) of 0.80 +/- 0.15 nM (mean +/- SEM) and a maximal binding capacity (Bmax) of 234.2 +/- 86.9 fmol/mg protein (mean +/- SEM). Among five of the nonsecreting pituitary adenomas examined, two had SRIH receptors with Kd values of 0.18 and 0.32 nM and Bmax values of 17.2 and 48.0 fmol/mg protein, respectively. In the remaining three, SRIH receptors were not detected. These results indicate that GH-secreting adenomas as well as some nonfunctioning adenomas have specific SRIH receptors, and hence, the function of the adenomas could be altered by SRIH.
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PMID:Specific somatostatin receptors on human pituitary adenoma cell membranes. 286 81

To investigate the mechanisms of gamma-aminobutyric acid (GABA) and benzodiazepine-induced growth hormone (GH) release, we studied the effects of GABA and a water-soluble benzodiazepine, midazolam, on basal immunoreactive somatostatin secretion from fetal rat brain in dispersed cell culture. Both GABA and midazolam in concentrations of 10(-5) or 10(-6) M inhibited basal somatostatin secretion from either diencephalic or cerebral neurons in culture. Midazolam (10(-5) M) produced a 33.2 +/- 8.6% suppression (P = 0.004) and 10(-5) M GABA produced a 46.0 +/- 4.3% suppression (P = 0.0003) in the diencephalon cultures. When GABA and midazolam were used in combination over the 10(-5)-10(-9) M range, the drugs were shown to act independently (positive main effect, P less than 0.0001 for either drug by two-way analysis of variance); there was a simple additive effect with no statistically significant interaction between the two drugs over the 36 combinations tested. These results suggest that suppression of the GH inhibitory peptide, somatostatin, may be one of the mechanisms by which GABA and benzodiazepines stimulate GH secretion. Based on previous studies of GABA and benzodiazepine receptors, it appears likely that these drugs produce this inhibitory effect by interacting with unassociated lower affinity receptors which require micromolar concentrations of the drugs, and act through calcium-dependent pathways.
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PMID:Influence of a benzodiazepine, midazolam, and gamma-aminobutyric acid (GABA) on basal somatostatin secretion from cerebral and diencephalic neurons in dispersed cell culture. 286 16

The influence of gamma-aminobutyric acid (GABA) on gastric somatostatin and gastrin release was studied using an isolated perfused rat stomach preparation. GABA dose-dependently inhibited somatostatin release (maximal inhibition of 44% at 10(-5)M GABA), whereas gastrin secretion was not affected. The GABA agonist muscimol led to a decrease in somatostatin release of similar magnitude. The GABA-induced changes were partially reversed by 10(-5)M atropine. Gastrin secretion was not influenced by either protocol. It is concluded that GABA as a putative neurotransmitter in the enteric nervous system is inhibitory to rat gastric somatostatin release in vitro via cholinergic pathways.
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PMID:Control of rat gastric somatostatin release by gamma-aminobutyric acid (GABA). 287 Sep 70

The effects of somatostatin (SOM) and cholecystokinin octapeptide (CCK-8) on basal and potassium-evoked release of neurotransmitter amino acids were investigated in slices of rat caudate nucleus (CN) and, for comparison, cerebral cortex (CX). Endogenous aspartate (Asp), glutamate (Glu), glycine (Gly), and gamma-aminobutyric acid (GABA) were measured by high performance liquid chromatography. In both CN and CX, potassium (5-55 mM) produced a concentration-dependent increase in the release of Asp, Glu, Gly, and GABA in the presence of extracellular Ca2+. CCK-8 (1 microM) stimulated in CN the basal and K+-evoked release of Gly to 231% and 160% of control, respectively; this effect was blocked by sulpiride (SULP), a dopamine receptor antagonist. In contrast, SOM (1 microM) inhibited the K+-evoked release of Glu in CN by 26%, an effect that was not blocked by SULP. SOM and CCK-8 did not significantly affect the basal or K+ (35 mM)-evoked release of other amino acids in the CN or of any amino acids in CX. The results indicate that: CCK-8 facilitation of Gly release is dependent of Gly release is dependent on dopamine receptor activation, whereas the inhibition by SOM of Glu release is not: and the effects of SOM and CCK-8 are specific with respect to the brain region affected.
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PMID:Somatostatin and CCK-8 modulate release of striatal amino acids: role of dopamine receptors. 287 62

Somatostatin and gamma-aminobutyric acid (GABA) concentrations were evaluated in the brain of kindled rats treated chronically with carbamazepine and valproic acid. Kindled seizures were almost completely blocked by treatment with carbamazepine, whereas the effect of valproic acid was partial, suppressing only generalized seizures. The duration of after-discharge in amygdala was suppressed by carbamazepine not by valproic acid. Carbamazepine induced a decrease in immunoreactive somatostatin concentration and an increase in GABA concentration in the temporal cortex of kindled rats. Valproic acid induced only an increase in GABA concentration. The results suggest that somatostatin may be associated with the suppression of focal seizure in amygdala and GABA may have a role in the suppression of generalized seizures.
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PMID:Effects of carbamazepine and valproic acid on brain immunoreactive somatostatin and gamma-aminobutyric acid in amygdaloid-kindled rats. 287 90

Addition of gamma-aminobutyric acid (GABA) to antral mucosal fragments in short-term incubation results in dose-dependent and bicuculline-sensitive stimulation of gastrin release and inhibition of somatostatin release, respectively. These effects of GABA on antral gastrin and somatostatin release closely resembled the actions of cholinergic agonists on G- and D-cell function. The present study examines the possibility that the effects of GABA on antral peptide release may be mediated, in part, through stimulation of antral cholinergic neurons. Inclusion of either atropine or pirenzepine in incubation medium prevented GABA-induced stimulation of gastrin release and inhibition of somatostatin release. Addition of the acetylcholinesterase inhibitor, physostigmine, caused a leftward shift in the GABA dose-response curve and increased by 10-fold the sensitivity of the antral preparation to GABA stimulation. Studies with tetrodotoxin suggest that GABA-stimulated gastrin release is mediated through activation of neurons contained within the antral mucosal/submucosal fragments. Hexamethonium, the ganglionic nicotinic receptor antagonist, did not affect GABA-induced gastrin release. These results indicate that GABA affects antral gastrin and somatostatin release through stimulation of antral postganglionic cholinergic neurons.
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PMID:Cholinergic mediation of gamma-aminobutyric acid-induced gastrin and somatostatin release from rat antrum. 287 17


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