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)

Leucine-enkephalin, methionine-enkephalin, and morphine caused a reversible block of Ca2+ channel currents in neuroblastoma-glioma hybrid cells (NG108-15). The long-lasting (type 2) component of the Ca2+ channel current was blocked by leucine-enkephalin, while the transient (type 1) component was not affected. The enkephalin-induced blocking action was antagonized by naloxone and appears to be mediated by delta-opiate receptors. Two different aspects of the blocking effect were detected, a resting block and a recovery from block during prolonged depolarizing pulses. Recovery from block was more complete, and its time course was more rapid, with depolarization to more positive potentials. The dose dependence of the type 2 channel block at rest indicated a one-to-one binding stoichiometry, with an apparent dissociation constant of 8.8 nM. Somatostatin exerted a similar selective blocking action on the type 2 Ca2+ channel. The time- and voltage-dependent block of type 2 Ca2+ channels may provide a mechanism underlying the enkephalinergic presynaptic inhibition of transmitter release and the somatostatin block of pituitary growth hormone release.
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PMID:Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG108-15 cells. 243 4

This study examines the effects of somatocrinin (GRF) and somatostatin antiserum (ASS), jointly and separately on gastric and duodenal growth. 24-day-old rats received twice daily SC injections of saline or GRF (4 and 20 micrograms X kg-1) for 14 days. ASS was given IP every 2 days. Alone, GRF increased gastric fundus weight concomitantly with DNA, RNA and protein contents producing hyperplasia and hypertrophy within this gland. Alone, ASS increased RNA and protein cellular concentrations. Joint ASS and GRF treatment stabilized the weight and protein content of the fundus, while reducing RNA contents as well as RNA and protein concentrations. GRF alone caused significant increments in duodenal weight and protein content suggesting cellular hypertrophy. Growth hormone, gastrin, cholecystokinin and secretin may be considered as putative mediators of these trophic effects.
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PMID:Effect of somatocrinin and a somatostatin antiserum on duodenal and gastric growth in the rat. 243 13

Growth hormone releasing factor (GRF), a 44-residue peptide originally isolated from human pancreatic tumors, shows structural similarities to the members of the secretin-vasoactive intestinal peptide (VIP) peptides. This study was designed to determine the effects of human GRF (hGRF-(1-44] on pancreatic secretion in vivo in conscious dogs and in vitro in dispersed rat pancreatic acini. GRF given i.v. in graded doses in dogs caused a small but significant stimulation of pancreatic HCO3- and protein outputs and potentiated secretin- and cholecystokinin (CCK)-induced pancreatic HCO3- but not protein secretion. When given together with somatostatin, GRF failed to reverse the inhibitory action of this peptide on HCO3- and protein responses to secretin plus CCK in dogs. Studies in vitro dispersed rat pancreatic acini showed that GRF added to the incubation medium of these acini caused an increase in basal amylase release and shifted to the left the amylase dose-response curve to caerulein and urecholine but failed to affect the amylase response to VIP. This study indicates that GRF in vivo stimulates basal and augments secretin- or CCK-induced pancreatic HCO3- secretion and that this is probably due to direct stimulatory action of the peptide on pancreatic secretory cells.
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PMID:Effects of growth hormone releasing factor on pancreatic secretion in vivo and in vitro. 246 9

Growth hormone (GH) release is influenced mainly by two hypothalamic factors, growth hormone-releasing factor (GRF) and somatostatin and is modulated by other hormones such as gonadal steroids. The objective of this study was to determine if castration (CA) and exogenous testosterone (TE) affect endogenous and GRF-induced GH release. Purebred Yorkshire male pigs (n = 32) were assigned to one of the following treatments: T1:CA; T2:CA +/- TE; T3: intact (IN); T4: IN +/- TE, in a 2 x 2 factorial design. Piglets were castrated at 3 days of age. Testosterone propionate (1.0 mg/kg) in sesame oil (2 ml) or sesame oil alone was injected sc SID during a 10-day period before each sampling day at 9, 15 and 21 weeks of age. Jugular blood samples were collected for a 6-hr period preceding and following iv injection of hGRF (1-29)NH2 (10 micrograms/kg). These procedures were repeated at 9, 15 and 21 weeks of age. The overall mean GH levels and the area under the GH peaks before and after GRF stimulation were lower (P less than .05) in castrated animals than in intact animals. Testosterone treatment increased (P less than .05) circulating TE levels and increased the amplitude of the endogenous GH peaks but did not affect (P greater than .05) the GRF-induced GH release. Increasing age produced a marked reduction of the amplitude of the GH peaks, the area under the GH peaks, the baseline mean and the overall mean GH levels during the 6-hr period preceding GRF injection. The present data support the hypothesis that castration in pigs reduces circulating and GRF-induced GH release. Exogenous testosterone for 10 days did not stimulate endogenous or GRF-induced GH release with the exception of the amplitude of the endogenous GH peaks.
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PMID:Castration and testosterone effects on endogenous and somatocrinin-induced growth hormone release in intact and castrated male pigs. 249 17

Growth hormone (GH) secretion is mediated by hypothalamic factors, mainly growth hormone releasing factor (GRF) and somatostatin (SS). The hypothalamic hormones, under direct neurotransmitter control, stimulate GH secretion through different central mechanisms. Atropine, an anticholinergic agent, can cross the blood-brain barrier and inhibit GH secretion stimulated by exercise and sleep in normal persons. In order to study the inhibiting effect of atropine on GH release and whether glucose can be replaced by atropine, normal persons and acromegaly patients were observed during exercise, after atropine, and 100 g glucose loading. The results confirmed that GH secretion increases after exercise and that this GH elevation can be inhibited by atropine in normal subjects. But in acromegaly patients high basal GH levels can not be inhibited by 100 g glucose loading or 0.6 mg atropine during the active phase of the disease. Blood sugar levels remained unchanged during the atropine test. It is suggested that the atropine test can be used as a GH inhibitory test in acromegaly patients with overt diabetes.
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PMID:Inhibitory effects of atropine on growth hormone release in normal subjects and acromegaly. 250 52

The effects of pituitary and pancreatic hormones on the change in hepatic cytochrome P450s were studied in alloxan- or streptozotocin-induced male rats. In two major sex-specific forms, P450-male and P450(6 beta-1), the former was decreased in chronic (5 week) diabetes to only less than one-third of controls and the latter was also reduced in early (1 week) diabetes. In contrast, a main phenobarbital-inducible form, P450b, was enhanced 25- to 30-fold in these diabetic rats. 3-Methylcholanthrene-inducible P448H was also elevated 3-fold in alloxan-induced diabetes. These changes in hepatic contents of P450-male, P450-6 beta-1, and P450b, which are under the regulation of pituitary growth hormone, associated well with the reported results of time-dependent changes in growth hormone levels in diabetes (G.S. Tannenbaum (1981) Endocrinology 108, 76-82), suggesting that the change in growth hormone level is a factor responsible for alterations in hepatic cytochrome P450s. Normalizing effects of insulin on these forms were also studied. Treatment of diabetic rats with insulin reversed the decreased amounts of both P450-male protein and mRNA. Insulin also normalized hepatic contents of P450b, P4506 beta-1, and P448H. However, the treatment of hypophysectomized rats with insulin had no effect, and treatment of diabetic rats with growth hormone or a suppressing agent of somatostatin, cysteamine, showed trivial effects on P450-male and P450b. These results suggest that insulin does not act directly as a substitute of growth hormone, but exerts its effect indirectly through the normalization of a growth hormone-mediated process(es) in diabetic rats.
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PMID:Cytochrome P450 in livers of diabetic rats: regulation by growth hormone and insulin. 252 54

Growth hormone secretion was stimulated in vitro by products of arachidonic acid epoxygenase, the epoxyeicosatrienoic acids. 5,6-Epoxyeicosatrienoic and 14,15-epoxyeicosatrienoic acid stimulated growth hormone release from an enriched population of somatotrophs (approximately 85%) by twofold. Inhibition of arachidonic acid metabolism by indomethacin did not affect growth hormone-releasing hormone stimulation of growth hormone release. In contrast, pretreatment of somatotrophs with an 11,12-isonitrile analogue of arachidonic acid that inhibits arachidonic acid epoxygenase, resulted in a 20-25% inhibition of growth hormone-releasing hormone-stimulated growth hormone release. 14,15-Epoxyeicosatrienoic acid stimulated a concentration-dependent increase (twofold) in the cytoplasmic concentration of adenosine 3',5'-cyclic monophosphate (cAMP) in the somatotrophs. 14,15-Epoxyeicosatrienoic acid also rapidly increased the intracellular free calcium concentration in somatotrophs from resting levels (approximately 80 nM) to greater than 250 nM. Growth hormone-releasing hormone increased the free intracellular calcium to 160-180 nM. Preincubation of somatotrophs with somatostatin inhibited growth hormone-releasing hormone-stimulated growth hormone secretion, cAMP accumulation, and 14,15-epoxyeicosatrienoic acid stimulated cAMP accumulation. These data are suggestive that the epoxyeicosatrienoic acids may have a role in the secretion of growth hormone.
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PMID:Effect of epoxyeicosatrienoic acids on growth hormone release from somatotrophs. 256 27

Growth hormone (GH) has long been considered to have importance in diabetes. With poor control in Type 1 diabetes GH levels are high and may aggravate poor metabolic control. Pharmacological suppression of GH release at this stage might reverse the metabolic changes, with the possible added benefit of lower plasma insulin concentrations. Diabetic patients with life-long GH deficiency rarely develop retinopathy, while pituitary ablation in patients with retinopathy often leads to improvement. Growth hormone release inhibiting factor, somatostatin, has a short plasma half-life, and multiple effects on the endocrine system and on the gastrointestinal tract, making it unsuitable for clinical use as a GH suppressant. Long-acting analogues have a long half-life, but remain non-specific in their effects. In Type 2 diabetes the analogue Octreotide suppresses insulin and glucagon release, leaving glucose levels either unchanged or somewhat elevated. Gastrointestinal side-effects have been common, but may diminish with long-term treatment. In Type 1 diabetes insulin requirement is decreased by Octreotide, but as in Type 2 diabetes GH suppression has been observed consistently only when the drug was given at bed-time. The decrease in insulin requirement may reflect suppression of glucagon release and/or gut effects. Amelioration of the 'dawn phenomenon' has not proved possible, and hypoglycaemia has proved a particular problem with Octreotide given subcutaneously at night. The lack of effective GH suppression (particularly in patients with proliferative retinopathy), lack of specificity, and the gut and hypoglycaemic side-effects, argue strongly against a clinical role for the current somatostatin analogues in diabetes mellitus.
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PMID:Somatostatin analogues in diabetes mellitus. 256 19

Previous research has established that growth hormone pulse amplitude declines with increasing age. The purpose of this study was to determine whether this decline is associated with (1) increased pituitary response to somatostatin, and/or (2) increased number or affinity of pituitary somatostatin receptors. In the first study, pituitary slices from young (3-4 months), middle-aged (12-14 months), and old (22-24 months) male Fischer 344 rats were superfused with minimal essential medium (1 ml/min) and fractions collected at 5-min intervals. Tissues were stimulated with 10(-7) M hpGRF (1-44) for 1 min and, 40 min later, with hpGRF in the presence of 5 x 10(-9) M somatostatin-14 or somatostatin-28. Two pituitaries from each age group were superfused simultaneously and the experiment replicated 4 times. Growth hormone release was measured by radioimmunoassay. In a second study, somatostatin receptors in purified pituitary membranes from the three age groups were compared using iodo-[Tyr0]-D-Trp8 somatostatin-14. Animals from each age group were pooled, membranes extracted, and incubated with increasing doses of cold peptide. Binding characteristics were analyzed by Scatchard analysis and Ka and Bmax calculated. Results indicated that (1) basal growth hormone release diminished both with age and somatostatin administration, (2) GRF-induced release of growth hormone was similar in all age groups when data were expressed as percent increase from baseline, and (3) in the presence of somatostatin-14, GRF-induced release of growth hormone was attenuated in old as compared to young or middle-aged rats (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased pituitary response to somatostatin in aging male rats: relationship to somatostatin receptor number and affinity. 257 35

As growth hormone has been implicated in the "dawn phenomenon," an early morning rise in serum glucose, we have studied the control of growth hormone release in diabetes using an acutely dispersed system of adenohypophysial cells from normal or diabetic rats (65 mg/kg streptozotocin, 8 days before sacrifice; serum glucose, 490 +/- 17 mg/dL). Growth hormone release is normally controlled by the two hypothalamic hormones, growth hormone releasing factor and somatostatin. We have found cells of the diabetic rats exhibit changes in sensitivity that result in increased growth hormone release in static incubation. In normal cells, rat growth hormone releasing factor increases growth hormone release three- to four-fold with an EC50 of 151 +/- 27 pM (n = 7). In contrast, in cells from diabetic rats, there was a significant (twofold) increase in sensitivity to growth hormone releasing factor (EC50 = 75 +/- 15 pM, n = 7) which resulted in increased growth hormone release with lower but not maximal (10 nM) growth hormone releasing factor. Basal nonstimulated release was unchanged. Somatostatin inhibition of stimulated growth hormone release was reduced (n = 7); half-maximal inhibition occurred with 0.21 +/- 0.03 nM (normal) and 0.76 +/- 0.17 nM somatostatin (diabetic). In perifusion the peak secretion rate was significantly lower for diabetic cells stimulated by a maximal dose of growth hormone releasing factor. These studies suggest somatotrophs of diabetic rats have altered sensitivity in vitro to the controlling hormones growth hormone releasing factor and somatostatin.
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PMID:Altered release of growth hormone from dispersed adenohypophysial cells of streptozotocin diabetic rats. I. Effects of growth hormone releasing factor and somatostatin. 257 47


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