Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A possible role of low pH in secretory vesicles for processing and secretion in the neurohypophysis was investigated. Subcellular fractionation of guinea-pig neural lobes revealed that a proton present in the membranes from this tissue could not be ascribed to secretory vesicles. However, a proton pump was found in coated microvesicles. Secretory vesicles isolated from rats and guinea pigs were stable under conditions known to lyse secretory vesicles from the adrenal medulla owing to the generation of a proton gradient. These results suggest that the internal pH of secretory vesicles from the neurohypophysis is closer to neutral than is the pH in chromaffin secretory vesicles. Processing of a neurophysin-glycopeptide intermediate from the biosynthesis of vasopressin in intact secretory vesicles incubated in vitro was activated by the addition of NH4Cl, known to increase the intravesicular pH. This activation of neurohormone processing was also apparent in isolated nerve endings incubated in the presence of NH4Cl, suggesting that NH4Cl can also be used to increase the intravesicular pH in intact nerve endings. However, NH4Cl did not affect the secretion of neurohormones, indicating that a low intravesicular pH is not important for exocytosis in the neurohypophysis. Our results indicate that a low pH generated during processing by mechanisms other than ATP-dependent proton transport may inhibit the processing enzymes, thereby preventing extensive breakdown of neurohormone precursors.
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PMID:Processing and secretion in the neurohypophysis. Stability of isolated secretory vesicles and role of internal pH. 294 70

The general pharmacological properties of YJA 20379-1 (2-amino-4,5-dihydro-8-phenylimidazo[2,1-b]thiazolo[4,5-g]benzo thi azole), a novel proton pump inhibitor with antiulcer activities, were investigated in mice, rats, guinea pig and rabbits. YJA 20379-1 at oral doses of 50, 100 and 200 mg/kg did not affect the general behaviour, hexobarbital hypnosis, motor coordination and body temperature in mice. The drug does not have analgesic and anticonvulsant action at 200 mg/kg p.o. The locomotor activity was not affected at 100 mg/kg p.o., but at 200 mg/kg, the activity was suppressed. YJA 20379-1 (at 2 x 10(-4) g/ml) did neither produce any contraction nor relaxation of isolated organs such as rat fundus, rat uterus, guinea pig ileum and guinea pig vas deferens, and the drug did not antagonize the contractile response to several spasmogens, such as histamine, acetylcholine, serotonin and oxytocin, and the drug up to 200 mg/kg p.o. did not affect pupil size of mice. The intestinal propulsion in mice was not affected up to 200 mg/kg p.o. The gastric emptying in rats was not affected at 100 mg/kg p.o., even if retardation in gastric emptying occurred at 200 mg/kg. YJA 20379-1 did not show anti-inflammatory action nor did it affect urinary excretion up to 200 mg/kg p.o. From these results, it is suggested that YJA 20379-1 at the high dose of 100 mg/kg p.o. may not exert any adverse effects.
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PMID:General pharmacological properties of YJA 20379-1, a novel proton pump inhibitor with antiulcer activities. 1063 48

The general pharmacological properties of YJA20379-2 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol[1,2-a]++ +benzoimidazole, a novel proton pump inhibitor with antiulcer activities were investigated in mice, rats, guinea pigs and rabbits. YJA20379-2 at oral doses of 50, 100 and 200 mg/kg did not affect the general behaviour, hexobarbital hypnosis and motor coordination in mice. The drug did not have analgesic or anticonvulsant action at 200 mg/kg. Locomotor activity and body temperature were not influenced at 100 mg/kg. At a concentration up to 2 x 10(-4) g/ml, YJA20379-2 did not produce any contraction or relaxation of isolated preparations, such as the rat fundus, the guinea pig ileum and the rat uterus, and did not antagonize the contractile response to several spasmogens, such as histamine, acetylcholine, serotonin and oxytocin. At dosages up to 200mg/kg p.o. YJA20379-2 did not affect the pupil size of mice. Intestinal propulsion of mice was not affected up to 200 mg/kg p.o. and the drug did not affect urinary excretion at 100 mg/kg p.o. These results indicate that at dosages up to 100 mg/kg p.o. YJA20379 was found not to affect this pharmacological profile. However, at 200 mg/kg the drug lowered body temperature and showed decreases in locomotor activity and urine volume.
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PMID:General pharmacological properties of YJA20379-2, a new antiulcer agent. 1072 61

Oxytocin (Oxt) is considered as a potential agent to treat multiple neuropsychiatric disorders, obesity and metabolic syndrome. Although the mechanisms underlying these effects remain unclear, nasal administration is considered to be a potential way to deliver Oxt into blood vessels. The development of an easier, more stable and efficient way is expected. A recent study demonstrated that orally administered Oxt can be transmitted into blood if it is prevented from degradation in stomach and reaches the intestinal tract. In this study, we pretreated mice with a proton pump inhibitor (PPI), omeprazole (20 mg/kg), and administered capsulized Oxt (0.25 mg), so that the Oxt can be prevented from degradation by pepsin due to the low pH in stomach and reach the intestinal tract. Functionally, these mice showed a similar decrease in food intake to those who underwent intraperitoneal administration. We also confirmed that this method dramatically increased plasma Oxt levels and the expression of neural activation marker c-Fos protein in the paraventricular and suprachiasmatic nucleus. Our study showed that by pretreating mice with PPI, Oxt in a gelatin-coated capsule can prevent Oxt from degradation by pepsin in stomach, and reach the bloodstream in an effective concentration. These results indicate that our method is a promising oral delivery of Oxt and should be investigated further for other peptide agents based on peripheral injection or nasal administration.
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PMID:Oral oxytocin delivery with proton pump inhibitor pretreatment decreases food intake. 3229 73