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 effect of exogenous insulin on secretion vesicle margination and secretion vesicle lysis in isolated perifused rat pancreatic islets. Recruitment of somatostatin (SRIF) receptors to the plasma membrane was used as a marker of secretion vesicle margination, whereas insulin release reflected the process of secretion vesicle lysis. A newly designed perifusion protocol allows one to interrupt intermittently either secretion vesicle margination or secretion vesicle lysis. Islets were initially perifused with glucose (30, 100, 165, 200, or 300 mg/dl) in the presence of sodium isethionate. Sodium isethionate inhibits secretion vesicle lysis, but not the recruitment of SRIF receptors. Thus, the margination of secretion vesicles to the surface membrane continued without their lysis. Sodium isethionate was then removed, and islets were challenged with 400 microM isobutylmethylxanthine (IBMX). In the islets perifused with high glucose concentrations, IBMX lysed a greater number of vesicles and caused enhanced release of insulin. The presence of exogenous insulin during the initial phase of secretion vesicle margination did not affect subsequent IBMX-induced insulin secretion from the islets perifused with low glucose concentrations (30 or even 100 mg/dl). When the glucose concentration was increased to 165, 200, or 300 mg/dl, insulin significantly diminished IBMX-induced insulin release. In separate experiments, increasing concentrations of insulin (50, 100, and 200 microU/ml) reduced glucose-induced recruitment of SRIF receptors in a dose-dependent manner. Our observations strongly suggest the existence of a well balanced relationship between ambient glucose and insulin concentrations in terms of their positive and negative feedback actions on insulin release. Their influences seem to be exerted at the level of secretion vesicle margination at the plasma membrane.
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PMID:Feedback inhibition of insulin on insulin secretion in isolated pancreatic islets. 241 17

Somatostatin receptors appear to be localized to secretory granules in pancreatic islet homogenates. Recruitment of these receptors to the islet-cell surfaces may mark the contact event between secretory granules and plasma membranes before release of insulin by fission. Isethionate, an impermeant anionic replacement for chloride, blocks the release step but does not affect receptor recruitment. By contrast, low concentrations of phenothiazine drugs, such as trifluoperazine and promethazine, inhibit both receptor recruitment and secretion. Scatchard analysis of phenothiazine effects on somatostatin receptors reveals that these drugs reduce the number of receptors but do not affect the affinity of the receptor for somatostatin. These data indicate that membrane contact and fission steps during exocytosis can be biochemically separated.
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PMID:Differential control of insulin secretion and somatostatin-receptor recruitment in isolated pancreatic islets. 631 Nov 75

Recruitment, migration and adherence of macrophages and their interaction with inoculated promastigotes are key steps in the initiation of the inflammatory process in cutaneous leishmaniasis. Parasite- and nervous system-derived factors might be involved in this process. In the present study the chemotactic activities of live, killed and sonicated Leishmania major promastigotes and of the promastigote culture supernatant as well as the L. major surface protease gp63 towards a murine macrophage cell line, Raw 264.7, were investigated, using the Boyden technique. The sensory neuropeptides SOM, CGRP and SP, and the autonomic neuropeptides VIP and NPY, were also investigated for possible modulatory effects on this chemotaxis, using the living promastigotes. Living promastigotes were the most efficient attractants for macrophages compared with other forms of the parasites. Prior incubation of the macrophages with the parasites completely abolished the chemotactic activity. This might indicate that the living promastigote chemotaxis is a receptor-mediated process. On the other hand, paraformaldehyde-killed promastigotes not only failed to induce macrophage chemotaxis but also inhibited it in comparison with the control. The surface protease gp63 tended to inhibit the macrophage chemotactic activity and the sonicate tended to stimulate it compared with controls. The culture supernatant had no effect, indicating that the chemoattractive factors putatively synthesized by the living promastigotes are not released to the surrounding medium. Somatostatin inhibited L. major promastigote-induced macrophage migration at a high concentration, 10(-6) M, while substance P inhibited it at both low concentrations, 10(-10) and 10(-9) M, and a high one, 10(-6) M, the last-mentioned having the greatest inhibitory effect. A stimulatory effect of calcitonin gene-related peptide was found at high concentrations, 10(-5) and 10(-6) M. Vasoactive intestinal peptide stimulated macrophage chemotactic activity at both a high, 10(-5) M, and at a low, 10(-9) M, concentration, the same concentration at which neuropeptide Y exerted its maximum inhibitory effect.
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PMID:In vitro Leishmania major promastigote-induced macrophage migration is modulated by sensory and autonomic neuropeptides. 971 14

Recruitment of the SH2 domain containing cytoplasmic protein-tyrosine phosphatase SHP-1 to the membrane by somatostatin (SST) is an early event in its antiproliferative signaling that induces intracellular acidification-dependent apoptosis in breast cancer cells. Fas ligation also induces acidification-dependent apoptosis in a manner requiring the presence of SHP-1 at the membrane. Moreover, we have recently reported that SHP-1 is required not only for acidification, but also for apoptotic events that follow acidification (Thangaraju, M., Sharma, K., Liu, D., Shen, S. H., and Srikant, C. B. (1999) Cancer Res. 59, 1649-1654). Here we show that ectopically expressed SHP-1 was predominantly membrane-associated and amplified the cytotoxic signaling initiated upon SST receptor activation and Fas ligation. The catalytically inactive mutant of SHP-1 (SHP-1C455S) abolished the ability of the SST agonists to signal apoptosis by preventing the recruitment of wild type SHP-1 to the membrane. Overexpression of the anti-apoptotic protein Bcl-2 in MCF-7 cells inhibited SST-induced apoptosis upstream of acidification by inhibiting p53-dependent induction of Bax as well as by raising the resting pH(i) and attenuating SST-induced decrease in pH(i). By contrast, Bcl-2 failed to prevent apoptosis triggered by direct acidification. These data demonstrate that (i) membrane-associated SHP-1 is required for receptor-mediated cytotoxic signaling that causes intracellular acidification and apoptosis, and (ii) Bcl-2 acts distal to SHP-1 and p53 to prevent SST-induced acidification but cannot inhibit the apoptotic events that ensue intracellular acidification.
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PMID:Regulation of acidification and apoptosis by SHP-1 and Bcl-2. 1050 21