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)

Prosomatostatin (pro-S) and its bioactive posttranslational products, somatostatin-14 (S-14), somatostatin-13 (S-13), and somatostatin-28 (S-28), were measured in human plasma by the use of immunoglobulins to the NH2-terminus of S-28 conjugated with agarose to separate them and, thereafter, by RIA with an antiserum recognizing the COOH-terminus of pro-S, and by specific RIA for the NH2-terminus of S-14 and pro-S. In healthy men, mean basal levels of pro-S were 4 pg equivalent S-14/ml; S-14/S-13 combined were 9 pg equivalent S-14/ml; and S-28 levels were 16 pg/ml. After a 700-kcal meal, pro-S, S-14, and S-14/S-13 did not change, whereas S-28 levels doubled by 120 min and remained elevated for 240 min. To evaluate the origins of these peptides, their levels were compared in peripheral, portal, gastric, and mesenteric veins of anesthetized patients and in patients with total resection of stomach and pancreas before and after nutrient intake. The stomach and small intestine were sources of both peptides; however, most S-28 originated in the small intestine. These findings suggest that, in contrast to S-14, S-28 is a hormone and may modulate postprandial nutrient absorption and use.
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PMID:Circulating prosomatostatin-derived peptides. Differential responses to food ingestion. 256 43

A series of six synthetic octapeptides, structurally related to somatostatin, demonstrate high affinity and selectivity for mu opioid receptors in radioligand binding assays. The compounds, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (CTP), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), D-tetrahydroisoquinoline carboxylic acid (D-Tic)-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (D-Tic-CTP), D-Tic-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (D-Tic-CTOP) and D-Tic-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (D-Tic-CTAP), were tested in vitro and in vivo for agonist and antagonist potency and selectivity. In vitro bioassays included the guinea pig ileum, mouse vas deferens and rabbit vas deferens. In vivo tests included hotplate antinociception and gastrointestinal transit inhibition, performed in mice. In vitro, all six derivatives were competitive, highly selective mu antagonists (pA2 values from 6.4-7.9). The compounds demonstrated varying degrees of intrinsic agonist activity especially in the mouse vas deferens, the least active being CTAP and D-Tic-CTAP, which showed no mu or kappa agonist actions, and delta activity only at very high (greater than 3 microM) concentrations. In vivo, none of these compounds showed antinociceptive actions when administered i.c.v. in mice. All were competitive mu antagonists in the hotplate antinociception test.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Novel peptidic mu opioid antagonists: pharmacologic characterization in vitro and in vivo. 256 79

This study examined the effects of chronic deletion of circulating growth hormone-releasing (GHRH) and/or somatostatin (SRIF) on normal growing male rats, as well as the effects of exogenous GHRH (1-29)NH2 and/or SMS 201-995 administration on the growth of rats with hypothalamic ablation. Passive immunization with anti-rat GHRH goat gamma-globulin (GHRH-Ab) for 3 weeks caused a marked decrease in the levels of pituitary GH mRNA and severe growth failure. Treatment with anti-SRIF goat gamma-globulin (SRIF-Ab) for 3 weeks produced a more modest decrease in GH mRNA levels in the pituitary and a slight but significant inhibition of normal somatic growth. Hypothalamic ablation produced a marked decrease in the level of mRNA in the pituitary. Chronic continuous administration of GHRH (1-29)NH2 stimulated pituitary GH synthesis, elevated serum levels of insulin-like growth factor I and increased body weight gain in rats with hypothalamic ablation treated with replacement doses of cortisone, testosterone and L-thyroxine. Combined treatment with GHRH (1-29)NH2 and SMS 201-995 appeared to promote the effect of GHRH on pituitary GH release and somatic growth in these animals. The results suggest that continuous administration of GHRH will be useful in the treatment of children with growth retardation resulting from hypothalamic disorders. In children with combined GHRH and somatostatin deficiencies, the addition of somatostatin to a GHRH treatment regimen may produce better results.
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PMID:GHRH treatment: studies in an animal model. 256 26

Three experiments were conducted with growing pigs actively immunized against a protein-conjugated somatostatin (SRIF) in Freund's adjuvant. In the first experiment, blood from 24-week-old pigs (seven immunized and eight control) was sampled at 20-min intervals for 6 h to evaluate basal GH concentrations. The animals were then injected iv with porcine GH-releasing factor (GRF)-(1-29)NH2 (10 micrograms/kg). Before GRF stimulation, immunized animals had higher (P less than 0.05) baseline mean GH levels (2.6 vs. 1.4 ng/ml) and area under the GH curve (AUC; 1632 vs. 779 ng/min.ml); they also had higher AUC after GRF administration (4268 vs. 1972 ng/min.ml). In a second experiment eight immunized and eight control pigs were injected iv four times at 90-min intervals with porcine GRF (10 micrograms/kg). Control pigs responding to the first injection did not respond to the second and third, and those responding to the second did not respond to the first, third, and fourth, indicating a decreased responsiveness that was longer than 3 h post-GRF response in control pigs. SRIF-immunized pigs had a more consistent GH response to the GRF injections. Overall, a reduced response was observed after the second and the fourth injections in immunized pigs, although five and six of eight animals had a GH peak response higher than 10 ng/ml during these periods. In a third experiment, effects of fasting, GRF, and SRIF immunization were studied. Immunization and fasting had their own positive effects on serum GH levels. Immunization increased baseline mean GH levels (5.0 vs. 2.2 ng/ml) and total AUC before (2318 vs. 1073 ng/min.ml) and after (1886 vs. 910 ng/min.ml) iv GRF stimulation (10 micrograms/kg) compared to controls. Fasting increased the mean baseline GH level (4.5 vs. 2.6 ng/ml), and it increased AUC before exogenous GRF stimulation (2009 vs. 1392 ng/min.ml). In conclusion, SRIF in pigs seems to be a potent GH-governing factor, since, when inhibited, baseline mean GH levels increase, and a consistent response to GRF is observed. Fasting could increase GH concentrations by different ways: decreasing SRIF release and increasing GRF release or modifying the sensitivity of the somatotrophs to both factors.
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PMID:Effects of active immunization against somatostatin on serum growth hormone concentration in growing pigs: influence of fasting and repetitive somatocrinin injections. 256 91

A series of heptapeptide somatostatin (SRIF) analogs containing mercaptopropionic acid (Mpa) and based on the parent structure Mpa-Tyr-[D]Trp-Lys-Val-Cys-Thr-NH2 were synthesized by solid-phase methodologies and assayed for their effects on rat growth hormone (GH) secretion and their ability to displace [125I]Tyr11-SRIF bound to various tissues in vitro. Structural modifications consisted primarily of aromatic substitutions for Thr. All analogs were less potent than SRIF in inhibiting GH secretion in vitro from 4-day primary cultures of rat pituitary cells (0.04-21% that of SRIF). Higher GH inhibitory potencies were observed in an acute 15 min in vivo potency assay probably reflecting increases in plasma half-life of the analogs as compared to native SRIF. All analogs had extremely low binding affinity for rat cerebral cortex (0.05-4% that of SRIF), while binding potency for rat pancreas ranged from 3-130% of SRIF. Several analogs exhibited enhanced binding to human small cell lung carcinoma cells (SCLC; NCI-H69) as compared to SRIF. One of these, containing Phe at the C-terminus, exhibited an affinity 3.5 X greater than SRIF itself and was further tested for possible effects on the proliferation of SCLC and rat pancreatic tumor cells (AR42J) in vitro. The proliferation of both tumor types was inhibited 32 and 60%, respectively (p less than 0.01). The data suggest that SRIF and certain analogs may have a direct action on proliferating tumors independent of endocrine effects and that the anti-tumor activity of SRIF analogs can be further dissociated from the other actions of native SRIF, thereby providing for potentially more selective therapeutic analogs.
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PMID:Novel heptapeptide somatostatin analog displays anti-tumor activity independent of effects on growth hormone secretion. 257 97

N intake in the form of protein has neither got an upper nor a lower limit for agricultural working animals within a diet and there is no control mechanism for it. A high surplus of certain amino acids results in a reduction of feed intake. N excretion in faeces depends on 1) the excretion of N containing indigestible feedstuffs, 2) bacterial nitrogen synthesis in the large intestine and 3) the excretion of true endogenous N containing substances (digestion enzymes, intestinal epithelium, N containing endogenous secretion). There are no other control mechanisms for N excretion in faeces. N excretion in urine mainly comprises the nitrogen from the degeneration of amino acids and nucleic acids. The interrelations between urea, NH3, allantoin, creatine and creatinine, uric acid and hippuric acid depend on the species (monogastric or ruminants), on the nitrogen and N amount consumed and on the recycling ratio of the amino acids. The absolute amount of N excretion is not subject to any control mechanism, it depends on the intake of protein and NPN substances, the interim stages, however, which lead to the formation of excretory products, are intermediately controlled. The most important interim stage is protein biosynthesis, which is a fixed, intermediately controlled value in maintenance level. Under growth conditions only, the protein synthesis quota can exceed the protein degradation quota of the total organism (positive N balance). The control mechanisms of protein biosynthesis have, according to current knowledge, the following structure: Stimulation: 1) growth hormone (STH) stimulates protein synthesis by means of somatomedins; 2) hormones of the thyroid gland (T4 and T3) are controlled by the hormone stimulating the thyroid gland (TSH); 3) insulin. Inhibition: 1) somatostatin inhibits STH, TSH and insulin; 2) cortisol directly inhibits protein synthesis and stimulates protein degradation. The control mechanisms of protein turnover in addition to genetic coding and proteolysis extend in the framework of evolution over the period of 3,400 million years from the existence of the bacterial cell to the development of mammals, which is 74% of the age of the earth and approximately 90% since the existence of the first traces of life. The control mechanisms of protein turnover in mammals do not permit gene manipulation in protein synthesis as in bacterial cells since the control mechanisms mentioned are missing there.
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PMID:[Nitrogen metabolism and its control mechanisms]. 266 79

The cytoprotective effect of a highly potent somatostatin (SRIF) analog, RC-121 (H-D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2), was examined in the absolute ethanol-induced gastric erosion model in rat. This analog diminished the degree of gastric erosion by 50-55% when administered in i.p. doses of 2 x 10(-10)-10(-8) g/100 g body weight, or in oral doses of 10(-8)-2 x 10(-7) g/100 body weight. The orally active, highly potent SRIF analogs may be useful as therapeutic agents in the treatment of human peptic ulcer.
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PMID:Protective effect of an orally administered, highly potent somatostatin analog (RC-121) against absolute ethanol-induced hemorrhagic erosions of the rat gastric mucosa. 273 41

Human pancreatic growth hormone-releasing factor (GRF-44-NH2) stimulated growth hormone (GH) secretion and intracellular cyclic AMP levels in cultured pituitary cells from both sheep and rat. Somatostatin (SRIF), over a wide range of doses and time, showed no significant effect on the elevated cyclic AMP levels in sheep cells, but did block the GH release in a dose-dependent manner. In rat cells, however, SRIF inhibited GRF-stimulated cyclic AMP levels by 75% maximum (still 8-fold greater than the basal levels) and GH release to almost half the basal value. We conclude that somatostatin inhibits GRF-elevated cyclic AMP levels in rat pituitary cells but not in sheep cells.
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PMID:Effects of growth hormone-releasing factor and somatostatin on growth hormone secretion and cellular cyclic AMP levels. Cultured ovine and rat anterior pituitary cells show markedly different responses. 285 5

A series of cyclic, conformationally restricted analogs of somatostatin have been prepared and tested for their ability to inhibit the binding of [3H]naloxone and [D-Ala2, D-Leu5] [3H]enkephalin to rat brain membranes. The most potent analog, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 where Pen is penicillamine in [D-Phe5, Cys6, Tyr7, D-Trp8, Pen11]somatostatin-(5-12)-octapeptide amide, exhibited high affinity for mu-opiate receptors (IC50 value of [3H]naloxone = 3.5 nM), being 7800 times more potent than somatostatin. The cyclic octapeptide also displayed high mu-opiate receptor selectivity with an IC50 [( D-Ala2,D-Leu5]enkephalin)/IC50 (naloxone) ratio of 271. The high affinity and selectivity of the somatostatin analog for mu-opiate receptors may be of use in examining the physiological role(s) of the mu-opiate receptor.
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PMID:Conformationally restricted analogs of somatostatin with high mu-opiate receptor specificity. 285 88

The effect of long-term administration of analogs of luteinizing hormone-releasing hormone (LH-RH) and somatostatin on the growth of the growth hormone (GH)- and prolactin (PRL)-secreting rat pituitary GH3 tumor was investigated. Daily administration of [D-Trp6]LH-RH (50 micrograms/day), early after inoculation of the GH3 tumor, inhibited tumor growth by more than 90% as compared to controls. Similarly, in two experiments, a single once-a-month injection of long-acting [D-Trp6]LH-RH microcapsules (in a dose calculated to release about 25 micrograms/day for 30 days) inhibited the growth of GH3 pituitary tumor by more than 50% 6 or 13 wk after transplantation, when the tumors were fully developed. Serum GH and PRL levels also were reduced markedly by treatment with [D-Trp6]LH-RH. On the other hand, the administration of an antagonistic analog of LH-RH, N-Ac-[D-Phe(4Cl)1,2, D-Trp3, D-Arg6, D-Ala10]LH-RH, did not significantly reduce the growth of this tumor, and the treatment with two different analogs of somatostatin, cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) and D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr NH2, appeared to enhance it. These results are in agreement with previous findings of growth inhibition of 7315a pituitary tumors with different hormone-secreting characteristics by agonistic analogs of LH-RH. The collective data from experimental work with rat pituitary tumor models support the contention that the use of [D-Trp6]LH-RH might be considered for the treatment of some patients with pituitary tumors who failed to respond to conventional therapy.
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PMID:Inhibition of growth of a prolactin and growth hormone-secreting pituitary tumor in rats by D-tryptophan-6 analog of luteinizing hormone-releasing hormone. 285 96


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