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)

It has been reported that somatostatin may be an effective antisecretory agent in a range of conditions causing severe secretory diarrhoea. In many children, intractable diarrhoeal illnesses result in significant morbidity and mortality. In a group of seven children with secretory diarrhoea, the effect of i.v. infusion of somatostatin (3.5 micrograms/kg stratum plus 3.5 micrograms/kg/h) on the net mucosal flux of salt and water was assessed using an in vivo steady-state perfusion technique. In one of the seven children who had evidence of deranged mucosal secretion and preserved villus function, somatostatin infusion resulted in a moderate reduction in secretion. In the remaining six, it had little or no beneficial effect. Somatostatin did not alter the rate of glucose absorption.
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PMID:The effect of somatostatin on small intestinal transport in intractable diarrhoea of infancy. 796 70

Cysteamine, a specific somatostatin depleter, was given to male rats to clarify its role in relation to the renin-angiotensin-aldosterone (RAA) axis and glomerulosa cell growth. Rats received seven daily sc injections of cysteamine at doses of 50 or 150 mg/kg body weight (BW). Their adrenal weights and whole cortical thickness increased, but zona glomerulosa thickness decreased dose-responsively. Plasma renin activity (PRA) and aldosterone concentration (PAC) decreased. Similar results were observed in rats on a low or high salt diet and receiving daily doses of 150 mg/kg BW of cysteamine. In hypophysectomized rats, however, cysteamine given for seven days at daily doses of 100 mg/kg BW did not change either PRA or PAC. Adrenal weight did not change either too. Our results indicate that cysteamine suppresses the RAA axis and glomerulosa cell growth, probably through pituitary factors.
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PMID:Effects of cysteamine, a somatostatin depleter, on the renin-angiotensin-aldosterone axis and glomerulosa cell growth in rats. 795 74

Hepatic transport of the synthetic somatostatin analog octreotide-SMS 201-995, (D)Phe-Cys-Phe-(D)Trp-Lys-Thr-Cys-Throl--and its novel derivative N-alpha-(alpha-D-glucosyl(1-4)-1-deoxy-D-fructosyl)-octreotide--SD Z CO-611, N-alpha-(alpha-D-glucosyl(1-4)-1-deoxy-D-fructosyl)-(D)Phe-Cys-Phe- (D)Trp-Lys-Thr-Cys-Throl--was studied. In rats SMS 201-995 showed a plasma elimination half-life of 1.2 +/- 0.2 hr; that of SDZ CO-611 was 1.9 +/- 0.3 hours. Within 120 min 66% of a mesenterically injected 4.4-nmol dose of SMS 201-995 was excreted in bile, but only 5.3% of SDZ CO-611 was excreted in bile. Biliary concentration of SMS 201-995 showed a maximum enrichment of 540-fold +/- 75-fold over peripheral blood concentration, indicating hepatic transport mechanisms different from simple diffusion. Comparison of plasma profiles of both peptides after mesenteric and femoral administration demonstrated the relative importance of hepatic extraction for SMS 201-995 but not for SDZ CO-611. The mode of extraction was studied by means of multiple-indicator dilution in isolated perfused rat liver, with inulin as nonpermeable marker. Ratio plots, ln([inulin]/[peptide]) vs. time, exhibited decreasing slopes for SMS 201-995, suggesting very rapid binding to hepatocyte membranes. The slope of the ratio plot of (inulin/SDZ CO-611) was almost zero even at low doses (down to 0.2 microgram), implying mainly extracellular distribution and nonhepatic elimination. Binding assays indicated the absence of somatostatin receptors in sinusoidal hepatocyte membranes. However, SMS 201-995 and SDZ CO-611 bound with high affinity to somatostatin receptors in rat cortical membranes. Multiple-indicator dilution experiments in presence of increasing cholyltaurine concentrations suggested an interaction of SMS 201-995 with sinusoidal bile salt transport. In isolated hepatocytes, uptake of SMS 201-995 was saturable and showed mutual inhibition with cholyltaurine. The results indicate that SMS 201-995 transport is different from receptor mediated endocytosis as known for peptide hormones and elimination pathways of SDZ CO-611 other than biliary excretion.
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PMID:Heterogeneity in hepatic transport of somatostatin analog octapeptides. 802 Aug 89

Under basal conditions, bile and bile salts applied intraduodenally influence plasma levels of several gastroenteropancreatic peptides. Besides those with stimulatory effects on exocrine pancreatic secretion, others with inhibitory or no effects are released as well. Furthermore, cholinergic and peptidergic neural mechanisms may also be activated. Secretin seems to be the most important mediator of bile- or bile salt-induced water and bicarbonate secretion. In addition, VIP released from peptidergic nerve endings in the pancreas may also be involved in the mediation of the hydrokinetic effect. With regard to water and bicarbonate secretion, cholinergic mechanisms probably are of minor importance. Cholinergic mechanisms, however, seem to be the most important mediator of bile- or bile salt-induced pancreatic enzyme secretion. CCK may act as an additional mediator of the ecbolic effect. This statement, however, is based on few results only and has to be confirmed by further studies. Gastroenteropancreatic peptides with an inhibitory action on the exocrine pancreas were also released by intraduodenal bile or bile salts. Somatostatin is released in physiologically relevant amounts to bring about a counter-regulation. Plasma PP levels are also enhanced by bile and bile salts. The amounts of PP released, however, are below those observed postprandially. In contrast to their stimulatory action on basal pancreatic secretion, bile and bile salts have no or even an inhibitory effect on pancreatic secretion stimulated by intraluminal nutrients. Accordingly, the release of gastroenteropancreatic peptides is not influenced (for example, secretin) or even reduced (for example, CCK) when bile or bile salts are added to intraluminal nutrients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The mediators of bile action on the exocrine pancreas. 809 58

A convenient synthetic method is described for the preparation of peptide-methotrexate (MTX) conjugates in which MTX is coupled selectively through the gamma-carboxyl group of its glutamic acid moiety to a free amino group in peptide analogs. The syntheses of a somatostatin analog-MTX conjugate (MTX-D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2) (AN-51) and two conjugates of analogs of luteinizing hormone-releasing hormone (LH-RH) with MTX [Glp-His-Trp-Ser-Tyr-D-Lys(MTX)-Leu-Arg-Pro-Gly-NH2] (AJ-04) and [Ac-Ser-Tyr-D-Lys(MTX)-Leu-Arg-Pro-NH-Et] AJ-51 are presented as examples. Benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent) was used in the synthesis for activation of 4-amino-4-deoxy-N10-methylpteroic acid, which reacted with the potassium salt of glutamic acid alpha-tert-butyl ester in dimethyl sulfoxide to form the suitably protected MTX derivative. This synthesis provides an example of the high suitability of BOP reagent for the salt-coupling method. The selectively protected MTX derivative was then coupled to the different peptide carriers and deprotected under relatively mild conditions by trifluoroacetic acid. The conjugates of MTX with hormonal analogs are suitable for targeting to various tumors that possess receptors for the peptide moieties.
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PMID:Selective coupling of methotrexate to peptide hormone carriers through a gamma-carboxamide linkage of its glutamic acid moiety: benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate activation in salt coupling. 810 Oct 4

We studied the effects of the 36-amino acid peptide, neuropeptide Y (NPY), on salt secretion by the rectal gland of Squalus acanthias. We used three preparations: whole isolated perfused glands, freshly prepared separated rectal gland tubules, and confluent monolayers of cultured rectal gland cells. In perfused glands NPY inhibited secretion stimulated by vasoactive intestinal peptide (VIP), forskolin, or adenosine 3',5'-cyclic monophosphate (cAMP) and theophylline. Maximal inhibition of 63 +/- 3.4% was seen at 3 x 10(-8) M NPY, with half-maximal effect at 3 x 10(-9) M. NPY did not inhibit the basal activity of rectal gland adenylate cyclase or that stimulated by VIP. The inhibitory action of NPY was not prevented by procaine, nifedipine, or diltiazem, suggesting that it was not secondary to the release of somatostatin or other unknown neurotransmitters from rectal gland nerves. In confirmation, somatostatin was not detected in the venous effluent after administration of NPY. NPY also inhibited transport-related oxygen consumption in separated rectal gland tubules and inhibited short-circuit current generated by confluent monolayers of primary cultures of rectal gland cells. The results indicate that NPY inhibits chloride secretion by a direct action on cells of the shark rectal gland at a site distal to the generation of cAMP.
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PMID:Neuropeptide Y inhibits chloride secretion in the shark rectal gland. 810 43

It has recently been demonstrated that the infusion of a high caloric load (3.3 kcal min-1 = 14.0 kJ min-1) into human upper jejunum inhibited pancreatic enzyme and bile salt secretion. The aim of the present study was to investigate whether this phenomenon was mediated by gastrointestinal hormones which interfere with pancreatic secretion. In six healthy volunteers, jejunal infusion of 1.3 kcal min-1 (5.5 kJ min-1) did not modify secretion of lipase and chymotrypsin to any significant extent compared with saline infusion, but the rate of 3.3 kcal min-1 (14.0 kJ min-1) resulted in an inhibition. Somatostatin and pancreatic polypeptide, which are known to inhibit exocrine pancreatic secretion, remained unchanged during jejunal nutrient infusion. The inhibition of pancreatic enzyme secretion was observed in temporal relationship with an increase of the stimulators of pancreatic exocrine secretion such as secretin, neurotensin, and CCK. The existence of an hitherto undefined inhibitor and a feedback mechanism is postulated.
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PMID:Effect of jejunal infusion of different caloric loads on pancreatic enzyme secretion and gastro-intestinal hormone response in man. 844 74

Insulin resistance has been demonstrated in patients with essential hypertension, and insulin-mediated sodium retention is believed to contribute to hypertension in these individuals. Recently, a hyperinsulinemic response to an oral glucose load has been found in salt-sensitive normotensive subjects, suggesting that insulin resistance may be present in these hypertension-prone individuals before the development of hypertension. In the present study, we examined the relation between insulin sensitivity and blood pressure response to salt intake in young, lean normotensive subjects on a high and a low salt diet. Insulin sensitivity was estimated by the "insulin suppression test," i.e., by measuring the plasma glucose and insulin concentrations achieved during a 180-minute infusion of somatostatin, insulin, and glucose in 18 healthy male volunteers (age, 21-28 years) given a standardized low salt diet (20 mmol/day) for 2 weeks, supplemented by either 220 mmol of NaCl per day or placebo in a single-blind randomized order for 1 week each. We defined salt sensitivity as a significant decrease in mean arterial blood pressure (> 3 mm Hg [p < 0.05]) measured for 60 minutes at 1-minute intervals on the low salt diet. By this definition, seven of the 18 subjects were salt sensitive. Although insulin infusion resulted in similar plasma insulin levels (approximately 50 milliunits/L) in both groups, concomitant glucose infusion resulted in plasma glucose levels that were more than 50% higher in the salt-sensitive than in the salt-resistant group (p < 0.005 by two-way analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin resistance in young salt-sensitive normotensive subjects. 847 36

1. The potential of bile salts to improve the enteral absorption of octreotide, an orally active somatostatin analogue, was investigated by a combination of in vitro, in situ and in vivo experiments. 2. Incorporation of octreotide into lipid monolayers (as measured by area increase of the monolayer at constant surface pressure using a Langmuir-Blodgett trough set-up) depended on the type of bile salt used for monolayer pre-treatment. Addition of 20 microM octreotide to the subphase containing 20 microM of the dihydroxylated bile salt ursodeoxycholate (UDCA) causes a 9% increase in area, whereas addition of octreotide to the subphase containing the 7 alpha-enantiomer of UDCA, chenodeoxycholate (CDCA), resulted in an area increase of the lipid monolayer of 20%. Area increase by octreotide alone was not significantly different from the increase of octreotide and UDCA in combination. 3. CDCA and UDCA in combination with octreotide increased the permeability of liposomal membranes for rubidium ions, whereas octreotide alone did not significantly change the permeability. This indicates membrane distortion as a possible cause for the enhanced absorption of octreotide by bile salts. 4. In polarized Caco-2 cell monolayers octreotide exhibited a permeation coefficient of 0.008 +/- 0.004 cm h-1. Addition of 0.2-1% of UDCA to the apical incubation medium had no significant effect upon the permeation coefficient. In contrast, 0.2-1% CDCA in the incubation medium resulted in a significant increase (P < 0.05) of the monolayer permeability of octreotide (0.015-0.037 cm h-1). 5. Octreotide was absorbed as the intact peptide from the gastrointestinal tract in rats with an absorption efficiency of 0.26%. Coadministration of bile salt resulted in a dose-dependent increase in absorption efficiency of the peptide up to 20.2%. The observed effect was more pronounced for CDCA than for UDCA. 6. The effect of CDCA and UDCA on octreotide absorption in vivo was assessed in a pharmacokinetic study with healthy volunteers. After oral administration of 4 mg octreotide in the presence of 100 mg bile salt, an average bioavailability of the peptide of 1.26% was achieved in the presence of CDCA, whereas in the presence of UDCA a bioavailability of only 0.13% was reached. This difference was statistically significant (P < 0.01). 7. In conclusion, the co-administration of CDCA is able to enhance the enteral absorption of octreotide. The in vitro and in situ experiments were predictive for the observed effect in human subjects.
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PMID:Permeation enhancement of octreotide by specific bile salts in rats and human subjects: in vitro, in vivo correlations. 882 66

To study the regulation of growth and differentiated function of insulin-secreting cells, the rat insulinoma cell line INS-1 was cultured in a defined serum-free medium containing prolactin, IGF-I, and triiodothyronine, which was originally reported to maintain insulin secretion of islet cells. Growth and viability, as well as cellular insulin content of INS-1 cells in the defined medium, were comparable to the control cells cultured in the complete medium containing 10% fetal calf serum. However, after a 3-day culture in this medium, insulin secretion in response to glucose, pyruvate, and leucine was markedly blunted compared with the control cells (-78, -68, and -56%, respectively), whereas the response to 30 mmol/l K+ was only slightly decreased. In these cells: 1) nutrient metabolism assessed by tetrazolium salt reduction was reduced in response to pyruvate and leucine, which are mainly metabolized in the mitochondria; 2) oxidation of both [3,4-(14)C]glucose and [1-(14)C]pyruvate was decreased (-22 and -32%, respectively); 3) glucose failed to depolarize the membrane potential, whereas tolbutamide was fully active; 4) video imaging analysis of cytosolic Ca2+ showed a decrease in the population of glucose-responsive cells, while the response to 30 mmol/l K+ was preserved; 5) serum replenishment for 3 days restored glucose-induced insulin secretion. Interestingly, conditioned serum-free medium from rat islets maintained the insulin secretory function of INS-1 cells, although glucagon, somatostatin, and some other factors failed to restore the function. In contrast, conditioned media from HepG2, PC12, and human umbilical vein endothelial cells did not substitute for serum. Thus, the impaired insulin secretion of the cells cultured in the defined medium is best explained by defective mitochondrial metabolism. Islet cells, but not INS-1 cells, produce factors required for normal signal generation by nutrient secretagogues.
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PMID:Glucose-induced insulin secretion in INS-1 cells depends on factors present in fetal calf serum and rat islet-conditioned medium. 928 42


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