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)

We have examined the actions of vasoactive intestinal peptide (VIP) and certain other known immune modulators on a nuclear pool(s) of protein kinase C (PKC) in isolated rat splenocyte nuclei. Rat splenocyte nuclei pure by enzymatic and electron microscope criteria demonstrated a time- and concentration-dependent activation of nuclear PKC (nPKC) by VIP. A biphasic pattern of three bell-shaped curves was observed with peak phosphorylation at 10(-15), 10(-9) and 10(-6)M VIP. The phosphorylation of endogenous nuclear substrates was characterized as a PKC-mediated event by use of three known PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), sphingosine, and staurosporine, which produced similar phosphate incorporation measurements. Also, this activity was blocked with the addition of a monoclonal antibody to PKC. Inhibitors of the ability of VIP to activate nPKC included somatostatin, 8-bromo-cAMP, peripheral benzodiazepine receptor modulators, and the PKC inhibitors, sphingosine and staurosporine. These data have direct relevance to our knowledge of cell-mediated immunity.
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PMID:Vasoactive intestinal peptide (VIP) activation of nuclear protein kinase C in purified nuclei of rat splenocytes. 197 36

Suppression of growth hormone by means of somatostatin has been suggested as a possible adjunct therapy in Type 1 diabetes. To assess the acute effect of the somatostatin analogue SMS 201-995 on kidney function in uncomplicated Type 1 diabetes, 13 normoalbuminuric, normotensive diabetic patients were investigated before and during IV infusion of SMS 201-995 (8 micrograms h-1). A control experiment with infusion of carrier only was also performed. The SMS infusion induced a reduction in the glomerular filtration rate (clearance of 125I-iothalamate) and renal plasma flow (131I-hippuran) from 140 +/- 15 (mean +/- SD) and 550 +/- 69 to 131 +/- 14 (2p less than 0.005) and 492 +/- 73 ml min-1 1.73-m-2 (2p less than 0.001), while filtration fraction and total renal resistance rose (both 2p less than 0.001). Urinary albumin excretion rate, blood pressure, and blood glucose concentration were unchanged. Plasma growth hormone and glucagon were significantly suppressed. The reduction in glomerular filtration rate and renal plasma flow correlated with the fall in glucagon concentration (r = 0.57, 2p = 0.04, and r = 0.63, 2p = 0.02). The urinary flow rate was markedly reduced, urine osmolality increased, and fractional excretion of sodium, calcium, and phosphate were reduced. Arginine vasopressin, atrial natriuretic peptide, angiotensin II, and aldosterone were unchanged by the SMS infusion. Thus SMS 201-995 acutely reduces glomerular filtration rate and renal plasma flow in uncomplicated Type 1 diabetes and has an antidiuretic effect. The effects may be related to suppression of glucagon secretion.
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PMID:Acute effects of a somatostatin analogue on kidney function in type 1 diabetic patients. 214 82

Mechanisms regulating peptidergic, noradrenergic and cholinergic development were compared in dissociated cell cultures of neonatal rat sympathetic ganglia. The majority of cultured neurons contained at least two neurotransmitters and many neurons contained three or more. These studies were undertaken to determine whether co-existing transmitters were co-ordinately regulated by the environment. Co-culture of sympathetic neurons with ganglion non-neuronal cells increased substance P and choline acetyltransferase activity but decreased somatostatin and tyrosine hydroxylase activity. Conversely, elimination of non-neuronal cells virtually abolished neuronal expression of substance P and choline acetyltransferase and increased somatostatin and tyrosine hydroxylase. Consequently, under these conditions, somatostatin and tyrosine hydroxylase were similarly regulated, whereas substance P was associated with choline acetyltransferase. By contrast, stimulation of adenylate cyclase or treatment with membrane-permeable adenosine 3',5'-phosphate analogs increased tyrosine hydroxylase and decreased choline acetyltransferase, but had no effect on substance P or somatostatin levels. Moreover, potassium- or veratridine-induced membrane depolarization increased tyrosine hydroxylase but decreased substance P, somatostatin and norepinephrine levels. However, inhibition of neurotransmitter release with magnesium or calcium-free medium prevented the decrease in norepinephrine levels but not the decrease in substance P and somatostatin. Consequently, the effects of membrane depolarization on peptide levels cannot be ascribed to release and subsequent depletion of substance P and somatostatin and must result from decreased net synthesis (synthesis minus catabolism) of the transmitters. Nerve growth-factor treatment also differentially regulated transmitter metabolism; nerve growth factor increased protein-specific activities of tyrosine hydroxylase and choline acetyltransferase but did not increase the protein-specific content of substance P and somatostatin. Quantitative transmitter expression was also influenced by neuron density; increasing density elevated substance P and choline acetyltransferase activity but decreased somatostatin and tyrosine hydroxylase activity per neuron. Finally, culture of sympathetic neurons in a defined (serum-free) medium also altered some but not all traits, decreasing substance P, somatostatin and choline acetyltransferase without any change in tyrosine hydroxylase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential regulation of peptide and catecholamine characters in cultured sympathetic neurons. 241 73

Static muscular contraction has been shown to increase cardiovascular and ventilatory function in reflex manner. The sensory arm of this reflex arc is comprised of group III and IV muscle afferents. The discharge properties of these muscle afferents whose activation causes the pressor reflex response to contraction were investigated. Group III afferents were more responsive to mechanical stimuli, such as tendon stretch and probing their receptive fields than were group IV afferents. In contrast, group III afferents were less responsive to ischemic contraction than were group IV afferents. Equal percentages of group III and IV afferents were stimulated by potassium, lactic acid and arachidonic acid, each of which are metabolic products of contraction. Adenosine, phosphate and lactate, however, had no effect on the discharge of the afferents. Intrathecal injection of antagonists or antibodies to substance P and somatostatin attenuated the pressor response to contraction by about half, a finding that suggests a role for these 2 peptides in the spinal transmission of the reflex.
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PMID:Pressor reflex response to static muscular contraction: its afferent arm and possible neurotransmitters. 245 28

The two mammalian neuropeptides substance P (SP) and neurokinin A (NKA) have been demonstrated to stimulate DNA synthesis in connective tissue cells, suggesting that peripheral neurons may play a role in development and tissue regeneration. In this study we have tried to identify intracellular messengers required for SP- and NKA-induced DNA synthesis. SP and NKA, as well as platelet-derived growth factor (PDGF) stimulated formation of inositol phosphates in smooth muscle cells (SMC), whereas no effect on inositol phosphates formation occurred in response to nonmitogenic neuropeptides. Pretreatment of the cells with pertussis toxin markedly decreased DNA synthesis induced by NKA. This toxin inhibits formation of inositol phosphates by acting on a regulatory G-protein. Calcium and calmodulin antagonists also inhibited NKA-induced DNA synthesis. These results imply that the mitogenic signal(s) produced by activated neuropeptide receptors involves formation of inositol phosphate and activation of a calcium/calmodulin dependent process. We further report that other neuropeptides occurring in peripheral neurons, i.e., vasoactive intestinal polypeptide, calcitonin gene-related peptide, neuropeptide Y, somatostatin, or cholecystokinin, are without growth-stimulatory effect on cultured SMC.
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PMID:Coupling between inositol phosphate formation and DNA synthesis in smooth muscle cells stimulated with neurokinin A. 245 38

The effects of somatostatin on catecholamine secretion and inositol phosphate accumulation have been studied using isolated perfused bovine adrenal glands and cultured bovine adrenal medullary cells. Somatostatin had no effect on basal adrenaline or noradrenaline secretion from either preparation. At concentrations above 1 microM, somatostatin inhibited the secretion of both catecholamines induced by 5 microM nicotine from cultured chromaffin cells. In contrast, over the concentration range 0.1 nM-10 microM, somatostatin had no effect on the secretory responses produced by 10 nM angiotensin II or 1 microM histamine. Inositol phosphate accumulation in cultured bovine adrenal medullary cells was unaffected by 0.1 nM-0.1 microM somatostatin, however at 1 and 10 microM somatostatin it was significantly increased, by 23% and 103% respectively. The effects of somatostatin (0.1 nM-10 microM) and of 50 microM muscarine on inositol phosphate accumulation were simply additive. Similarly, somatostatin at 0.1 nM and 10 nM together with 10 nM angiotensin II or 1 microM histamine produced additive inositol phosphate responses. In contrast, 1 microM somatostatin gave significantly more-than-additive (synergistic) inositol phosphate responses with angiotensin II and histamine. The results suggest that some adrenal medullary cells possess several types of receptors, and that these receptors may interact to produce non-additive responses.
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PMID:Actions of somatostatin on perfused bovine adrenal glands and cultured bovine adrenal medullary cells. 256 51

The concept of multifactorial pituitary control is now well established. As in other cell systems, integration of complex messages involves dynamic interactions of receptors and coupling mechanisms. Regulation of adenohypophyseal secretions has been shown to involve cyclic AMP production, the modulation of phosphatidylinositol phosphate breakdown and Ca2+ mobilization. Dopamine, somatostatin and angiotensin II receptors are negatively coupled to adenylate cyclase in anterior pituitary cells. In the case of angiotensin, this effect on adenylate cyclase appears paradoxical since the peptide markedly stimulates prolactin secretion. In fact, angiotensin II also markedly stimulates inositol phosphate production and this effect could account for the stimulated hormone secretion. In addition, dopamine could inhibit inositol phosphate production stimulated by angiotensin II and thyrotropin-releasing hormone. Dopamine and somatostatin also directly modulate voltage-dependent calcium channels, perhaps through a direct coupling with potassium channels. On the other hand, steroids modulate the sensitivity of adenohypophyseal cells to neurohormones by different mechanisms. In the case of somatostatin, it increases the number of specific binding sites, while in the case of dopamine estradiol affects the transduction mechanisms of D2 dopamine receptors. In conclusion, dopamine and somatostatin receptors appear coupled to various transduction mechanisms through pertussis-sensitive G proteins in anterior pituitary cells.
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PMID:Multiple transduction mechanisms of dopamine, somatostatin and angiotensin II receptors in anterior pituitary cells. 256 74

Male patients with recurrent calcium (Ca) urolithiasis (RCU) with idiopathic hypercalciuria (I-HC, n = 12) or normocalciuria (NC, n = 12), and age, sex, and weight-matched controls (C, n = 12) were evaluated before and after a carbohydrate-rich synthetic meal for blood glucose, free fatty acids (FFA), alpha-amino-nitrogen, several glucometabolic hormones and parathyroid hormone (PTH), and urine Ca, phosphate, oxalate, and cyclic adenosine monophosphate (cAMP) levels as well as saturation. Fasting serum Ca was significantly higher and PTH significantly lower in I-HC than in controls, whereas in fasting urine cAMP and phosphate were unchanged. There were only minor differences between fasting blood glucose levels and postprandial glucose tolerance of RCU patients and controls. However, serum insulin was significantly elevated in I-HC versus C, but serum C-peptide, plasma glucagon, and somatostatin levels were comparable in RCU and C. FFA were significantly lower in RCU than C. Postprandial phosphaturia and urinary saturation with Ca-phosphates were significantly higher in RCU versus C, whereas urinary cAMP, pH, and oxalate were similar. We conclude that: (1) in RCU patients some postabsorptive steps in glucose metabolism may be abnormal; (2) those with I-HC have enhanced postprandial Ca and phosphate excretion concomitantly with disordered insulin metabolism; and (3) RCU patients may suffer from a postprandial renal phosphate leak, which may make their urine more lithogenic.
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PMID:Blood levels of glucometabolic hormones and urinary saturation with stone forming phases after an oral test meal in male patients with recurrent idiopathic calcium urolithiasis and in healthy controls. 257 28

Ten male healthy volunteers were studied in order to determine whether the synthetic somatostatin analogue Sandostatin (SMS 201-995) has effects similar to those of natural somatostatin on renal water and electrolyte excretion. The study was carried out in three separate placebo-controlled randomized double-blind cross-over trials. The subjects received single sc injections of 100 micrograms Sandostatin and placebo under conditions of mild diuresis (trial 1), water load with enhanced diuresis (trial 2), and water load with exogenous lysin-vasopressin (5 IU sc) induced antidiuresis (trial 3). The following parameters were measured: urine flow rate, serum and urine osmolalities, osmolar clearance, free water and creatinine clearances, excretion rates of sodium, potassium, calcium, chloride, and phosphate, and immunoreactive insulin. A marked antidiuretic effect was observed within 2 h after dosing in all three trials. Urine flow rates were reduced by 45% in trial 1 and by 29 and 31% in trials 2 and 3, respectively (all P less than 0.05). There were no differences in effects on serum and urine osmolalities between Sandostatin and placebo. Osmolar clearance was significantly reduced in trial 1 (P less than 0.01). Free water clearance significantly decreased only in trial 2 (P less than 0.05). Sodium excretion decreased by 49, 48 and 67%, respectively, the differences being significant in trials 1 and 3 (P less than 0.05). Calcium excretion decreased by 66, 70 and 54% (all P less than 0.001). Chloride excretion decreased by 28, 22 and 44%, the differences being significant in trials 2 and 3 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antidiuretic effect of Sandostatin (SMS 201-995) in healthy volunteers. 265 54

The effect of a long acting somatostatin analogue SMS 201-995 on stomal effluents in patients with severe short bowel syndrome was investigated in a double blind placebo controlled balance study. Six patients, five with Crohn's disease and one with radiation enteropathy were studied. Five patients had a jejunostomy and one an ileostomy. The patients had a normal food intake, but because of severe malabsorption had received home parenteral nutrition for several years. Faecal mass was reduced (p less than 0.005) and intestinal net sodium absorption was increased (p less than 0.005) by intravenous infusion of SMS 25 micrograms/h. Net absorption of potassium, calcium, magnesium phosphate, zinc, nitrogen and fat was not influenced. Subcutaneous injections of 50 micrograms SMS every 12 hours had a similar effect on net intestinal absorption of sodium and water. Four patients continued with a five to six months open follow up study when subcutaneous SMS in the same dose was administered by the patients at home. The effect on faecal sodium loss persisted, but in one patient faecal mass gradually increased and finally exceeded pretreatment values. SMS may decrease net absorption of water and sodium following reduced secretion of digestive juices rather than by increasing absorptive capacity. SMS may be useful as an antidiarrhoeal drug in patients with high output jejuno- or ileostomies, but in patients who need permanent parenteral nutrition the effect is too small to significantly alter management.
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PMID:Effect of a long acting somatostatin analogue SMS 201-995 on jejunostomy effluents in patients with severe short bowel syndrome. 231 26


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