Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of somatostatin-14 and its biologically active analogs, RC-160 and SMS 201-995, on (Ca,Mg)ATPase activity in vitro were studied in homogenates of anterior pituitary cells. It was found that somatostatin inhibited the (Ca,Mg)ATPase activity in the anterior pituitary and somatostatin analogs exerted slight biphasic effects on the calcium pump activity. The effects of specific brain (Ca,Mg)ATPase inhibitors, VOSO4 and LaCl3, were also studied in vitro. Neither VOSO4 nor LaCl3 enhance the inhibition of calcium pump activity caused by somatostatin. It is suggested that somatostatin may mediate its action in pituitary cells, among others, by the regulation of (Ca,Mg)ATPase activity.
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PMID:Effects of somatostatin-14 and its analogs on the (Ca,Mg)ATPase in the rat anterior pituitary. 167 1

In order to explore the pathogenetic mechanism underlying the changes in blood-brain barrier sodium transport in experimental diabetes, the effects of hyperglycemia and of hypoinsulinemia were studied in nondiabetic rats. In untreated diabetes, the neocortical blood-brain barrier permeability for sodium decreased by 20% (5.6 +/- 0.7 versus 7.0 +/- 0.8 X 10(5) ml/g/s) as compared to controls. Intravenous infusion of 50% glucose for 2 h was associated with a decrease in the blood-brain barrier permeability to sodium (5.4 +/- 1.2 X 10(5) ml/g/s), whereas rats treated with an inhibitor of insulin-secretion (SMS 201-995, a somatostatin-analogue) had normal sodium permeability (7.3 +/- 2.0 X 10(5) ml/g/s). Acute insulin treatment of diabetic rats normalized the sodium permeability within a few hours as compared to a separate control group (7.7 +/- 1.1 versus 6.9 +/- 1.4 X 10(5) ml/g/s). To elucidate whether the abnormal blood-brain barrier passage is caused by a metabolic effect of glucose or by the concomitant hyperosmolality, rats were made hyperosmolar by intravenous injection of 50% mannitol. Although not statistically significant, blood-brain barrier sodium permeability increased in hyperosmolar rats as compared to the control rats (8.3 +/- 1.0 and 7.0 +/- 1.9 X 10(5) ml/g/s, respectively). It is concluded that either hyperglycemia per se or a glucose metabolite is responsible for the blood-brain barrier abnormality which occurs in diabetes. Further, we suggest that the specific decrease of sodium permeability could be the result of glucose-mediated inhibition of the Na+K+-ATPase localized at the blood-brain barrier.
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PMID:Blood-brain barrier permeability to sodium. Modification by glucose or insulin? 264 96

Brush border membrane vesicles (BBMV) and basolateral membrane vesicles (BLMV) were simultaneously prepared from surgically resected pieces of morphologically intact human duodenum with a modified Percoll gradient centrifugation method. Alkaline phosphatase was enriched 20-fold in BBMV, whereas (Na+ + K+)-stimulated adenosine triphosphatase was enriched 15-fold in BLMV. BBMV and BLMV were preincubated with 3 microM synthetic somatostatin-14 or 3 microM SMS 201-995 for 10 min at 5 degrees C. In BBMV calcium, sodium, D-glucose, L-alanine, and D-mannitol uptake was unaffected by somatostatin-14 and SMS 201-995. In BLMV we found two Ca++ transport systems: Na+/Ca++ exchange and ATP-driven Ca++ transport. Somatostatin-14 had no effect on either of the two transport mechanisms. SMS 201-995 had no effect on Na+/Ca++ exchange but significantly inhibited basolateral ATP-dependent Ca++ transport (-40% +/- 5%, p less than 0.005).
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PMID:Effect of the somatostatin analogue SMS 201-995 on ATP-dependent calcium transport of basolateral vesicles from human duodenum. 289 47

Gastric acid exerts a feedback inhibition on the secretion of gastrin from antral G cells. This study examines whether gastrin gene expression is also regulated by changes in gastric pH. Achlorhydria was induced in rats by the gastric H+/K+ ATPase inhibitor, omeprazole (100 mumol/kg). This resulted in fourfold increases in both serum gastrin (within 2 h) and gastrin mRNA levels (after 24 h). Antral somatostatin D cells probably act as chemoreceptors for gastric acid to mediate a paracrine inhibition on gastrin secretion from adjacent G cells. Omeprazole-induced achlorhydria reduced D-cell activity as shown by a threefold decrease in antral somatostatin mRNA levels that began after 24 h. Exogenous administration of the somatostatin analogue SMS 201-995 (10 micrograms/kg) prevented both the hypergastrinemia and the increase in gastrin mRNA levels caused by omeprazole-induced achlorhydria. Exogenous somatostatin, however, did not influence the decrease in antral somatostatin mRNA levels seen with achlorhydria. These data, therefore, support the hypothesis that antral D cells act as chemoreceptors for changes in gastric pH, and modulates somatostatin secretion and synthesis to mediate a paracrine inhibition on gastrin gene expression in adjacent G cells.
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PMID:Reciprocal regulation of antral gastrin and somatostatin gene expression by omeprazole-induced achlorhydria. 290 31

To clarify the effect of islet hormones on pancreatic ductular cell function, we measured the exocrine secretion elicited by 10 pM secretin in the presence or absence of islet hormones using an isolated perfused rat pancreas model. Insulin significantly increased secretin-stimulated pancreatic juice secretion, but not protein secretion. The potentiating effect of insulin on pancreatic juice secretion was concentration-dependent, and the maximal effect was observed with 1 microM insulin. Ouabain, a specific Na+,K(+)-ATPase inhibitor, caused concentration-dependent inhibition of the potentiating effect of insulin without affecting secretin action. Glucagon (100 nM) significantly inhibited secretin-stimulated pancreatic juice secretion and also tended to inhibit protein secretion. A somatostatin analog, SMS 201-995 (10 nM) significantly inhibited both the pancreatic juice and protein secretion stimulated by secretin. The inhibitory effect of SMS 201-995 was concentration-dependent and was maximal at 1-10 nM. These results demonstrate that insulin potentiates the secretory response to secretin, at least partly by increasing Na+,K(+)-ATPase activity, whereas glucagon and somatostatin inhibit this response. Thus, pancreatic islet hormones regulate the secretory function of pancreatic ductular and centroacinar cells.
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PMID:Effect of islet hormones on secretin-stimulated exocrine secretion in isolated perfused rat pancreas. 832 88

The intronic GGGGCC hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) is a prevalent genetic abnormality identified in both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Smith-Magenis syndrome chromosomal region candidate gene 8 (SMCR8) is a protein with unclear functions. We report that C9ORF72 is a component of a multiprotein complex containing SMCR8, WDR41, and ATG101 (an important regulator of autophagy). The C9ORF72 complex displays guanosine triphosphatase (GTPase) activity and acts as a guanosine diphosphate-guanosine 5'-triphosphate (GDP-GTP) exchange factor (GEF) for RAB39B. We created Smcr8 knockout mice and found that Smcr8 mutant cells exhibit impaired autophagy induction, which is similarly observed in C9orf72 knockdown cells. Mechanistically, SMCR8/C9ORF72 interacts with the key autophagy initiation ULK1 complex and regulates expression and activity of ULK1. The complex has an additional role in regulating later stages of autophagy. Whereas autophagic flux is enhanced in C9orf72 knockdown cells, depletion of Smcr8 results in a reduced flux with an abnormal expression of lysosomal enzymes. Thus, C9ORF72 and SMCR8 have similar functions in modulating autophagy induction by regulating ULK1 and play distinct roles in regulating autophagic flux.
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PMID:A C9ORF72/SMCR8-containing complex regulates ULK1 and plays a dual role in autophagy. 2761 92