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)

Neuropeptides may have functions in the central nervous system (CNS) other than altering neuronal excitability. For example, they may act as regulators of brain metabolism by affecting glycogenolysis. Since it has been suggested that glial cells might provide metabolic support for neuronal activity, they may well be one of the targets for neuropeptide regulation of metabolism. Consistent with this view are reports that peptide-containing nerve terminals have been seen apposed to astrocytes, but it is also quite possible that peptides could act at sites lacking morphological specialization. Primary cultures containing CNS glial cells have been shown to respond to beta-adrenergic agonists with an increase in cyclic AMP and, as a result, with an increase in glycogenolysis and have also been shown to respond to a variety of peptides with changes in cyclic AMP. In the study reported here, we have examined the effects of several peptides on relatively pure cultures of rat astrocytes. We demonstrate that the increase in intracellular cyclic AMP induced by noradrenaline is markedly enhanced by somatostatin and substance P and is inhibited by enkephalin, even though these peptides on their own have little or no effect on the basal levels of cyclic AMP. Vasoactive intestinal peptide (VIP) on the other hand increases cyclic AMP in the absence of noradrenaline. These results suggest that neuropeptides influence glial cells as well as neurones in the CNS and, in the case of somatostatin and substance P, provide further examples of neuropeptides modulating the response to another chemical signal without having a detectable action on their own.
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PMID:Neuropeptides modulate the beta-adrenergic response of purified astrocytes in vitro. 619 28

Vasoactive intestinal peptide (VIP) has been shown to increase cyclic AMP content in isolated epithelial cells of rat ventral prostate. The stimulatory effect of VIP was dependent on time and temperature and was potentiated by a phosphodiesterase inhibitor. At 15 degrees C, the response occurred in the 1 X 10(-10)-10(-7)M range of VIP concentrations. Half-maximal stimulation of cellular cyclic AMP was obtained at 1.4 nM and maximal stimulation (3-fold basal level) at about 100 nM VIP. Chicken VIP and porcine secretin were agonists of porcine VIP but exhibited a 2-times higher and a 170-times lower potency, respectively. A high concentration (1 X 10(-6)M) of glucagon, somatostatin, neurotensin, substance P, Met-enkephalin or Leu-enkephalin did not modify cAMP levels. The finding of a VIP-stimulated cAMP system in rat prostatic epithelial cells together with the previous characterization of high-affinity receptors for VIP in the same cell preparation, as well as the presence of VIP-containing neurones innervating the male genitourinary tract, strongly suggest that VIP may be involved in prostatic growth regulation and function.
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PMID:Cyclic AMP-stimulating effect of vasoactive intestinal peptide in isolated epithelial cells of rat ventral prostate. 631 52

Smooth muscle cells isolated by enzymatic digestion were used to determine the direct effects of galanin on circular and longitudinal muscle layers from dog proximal colon and to investigate the intracellular pathways involved in these effects. Effects of galanin were compared to those observed with other contracting [cholecystokinin octapeptide (CCK8)] and relaxing [vasoactive intestinal peptide (VIP)] agents. In longitudinal cells, galanin and CCK8 induced a contraction that was maximal at 1 nM galanin and 1 nM CCK8 and was 23.9 +/- 4.5% and 23.4 +/- 3.4%, respectively, of the length of resting cells. Incubation of cells in Ca(2+)-free medium or in the presence of nifedipine caused an inhibition of galanin-induced contraction whereas it had no effect on the contraction induced by CCK8. Vasoactive intestinal peptide, forskolin, and 8 bromo cAMP inhibited CCK-induced contraction but failed to inhibit contraction induced by galanin. The contraction induced by galanin was abolished; the CCK-induced contraction was unchanged by pertussis toxin. In circular cells, CCK8 induced a contraction that was maximal at 10 nM and was 24.2 +/- 2.6%. Galanin had no effect by itself. When cells were preincubated (1 min) with galanin (10 fM-1 microM), the CCK8-induced contraction was inhibited, with a maximal effect at 10 nM galanin. Likewise, VIP inhibited the CCK8-induced contraction with a maximal effect at 1 microM. Preincubation of cells with somatostatin, N-ethylmaleimide, and (R)-p-cAMPS inhibited galanin- and VIP-induced relaxation. In conclusion, galanin induces a contraction of longitudinal smooth muscle cells that is dependent on an influx of extracellular calcium and an activation of pertussis toxin G-protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Galanin induces opposite effects via different intracellular pathways in smooth muscle cells from dog colon. 752 50

Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide with a wide range of biological activities. Recent data suggest that functional VIP receptors are expressed on various tumor cells. Somatostatin (SST) and its long-acting analogue octreotide (OCT) are potent inhibitors of tumor cell growth and secretion. In the present study, the interactions between VIP and SST/OCT on primary tumors (insulinomas, n = 3; VIPomas, n = 2; intestinal adenocarcinomas, n = 5; neuroblastomas, n = 5; papillary thyroid cancers, n = 7; carcinoids, n = 5; ductal breast cancers, n = 8; small cell lung cancers, n = 3; ACTH-producing hypophyseal adenomas, n = 5; pheochromocytomas, n = 5) as well as on tumor cell lines (A431, HT29, PANC1, COLO320, HMC1, and KU812 cells) were analyzed by use of 123I-labeled VIP and 123I-labeled Tyr-3-OCT. Cross-competition between VIP and SST/OCT for binding to tumor cells was observed. The rank-order of potency for displacement of 123I-labeled VIP binding to intact A431 cells was VIP [concentration causing half-maximal inhibition (IC50) = 2.9 +/- 1.9 (SD) nM] > OCT (IC50 = 9.3 +/- 1.7 nM) = SST > substance P = secretin (IC50 = 1 microM). Binding of 123I-labeled Tyr-3-OCT to A431 cells, in turn, was inhibited by OCT = Tyr-3-OCT (IC50 = 1.5 +/- 0.3 nM) = SST > VIP (IC50 = 4.9 +/- 1.1 nM). This rank-order of potency was also obtained for primary tumors and tumor cell lines. Furthermore, SST and OCT inhibited VIP-induced [3H]thymidine incorporation, cyclic AMP formation, and tyrosine kinase activity with IC50 values < 10 nM. Together, these data provide evidence for functional interactions between SST and VIP on various tumor cells. These interactions may involve peptide cross-competition at cellular binding sites and may have implications for the biology and pathophysiology of respective cells and disease states.
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PMID:Cross-competition between vasoactive intestinal peptide and somatostatin for binding to tumor cell membrane receptors. 790 85

Vasoactive intestinal peptide (VIP) receptors were investigated in rat peritoneal macrophage membranes (RPMM) using [125I]VIP as ligand. The receptor binding was rapid, reversible, saturable, specific, and dependent on time, temperature, and membrane concentration. The Scatchard analysis of binding data was consistent with the existence of two classes of VIP binding sites with Kd values of 0.60 +/- 0.08 and 275 +/- 39 nM and binding capacities of 580 +/- 71 and 72,500 +/- 810 fmol VIP/mg protein, respectively. The interaction showed a high degree of specificity, as suggested by competitive displacement experiments with several peptides structurally or not structurally related to VIP. These pharmacological studies showed the following order of potency: VIP (IC50 = 1 nM) > rGRF (IC50 = 13 nM) > PHI (IC50 = 421 nM) >> secretin. Glucagon, somatostatin, insulin octapeptide of cholecystokinin [CCK(26-33)], and pancreastatin were ineffective at concentrations up to 1 microM. Binding of [125I]VIP to membranes is markedly reduced by increasing the ionic strength of incubation medium. Treatment of membranes with dithiothreitol, trypsin, and phospholipases A2 and C resulted in a loss of the ability of these membranes to bind VIP. However, treatment with phospholipase D did not affect binding of VIP by membranes. The molecular characterization of VIP receptors in RPMM was performed after [125I]VIP cross-linking to membranes using the cross-linker dithiobis (succinimidyl propionate). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane proteins revealed specific [125I]VIP-protein complexes of M(r) 55,000 +/- 1700, 35,000 +/- 900, and 22,000 +/- 500.
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PMID:Characteristics of receptors for VIP in rat peritoneal macrophage membranes. 800 37

Accurate and sensitive sandwich ELISA has been developed for the detection and identification of each of the three neuropeptides, namely, Vasoactive intestinal peptide, Somatostatin and Substance P. The neuropeptides conjugated with BSA and emulsified with Freund's adjuvant were used for immunisation of rabbits. Titres of polyclonal antibodies were checked by indirect immunofluorescence. The animals were bled when titres were high, sera separated, complement inactivated and IgG class of antibodies were purified using a protein G column. Purified IgG antibodies were used for coating the wells and for conjugation with HRPO and used for the detection of the synthetic neuropeptides in a standard solution or in the culture supernatant. The ELISA thus developed for the assay of each of the three neuropeptides had a sensitivity (0.01 ng - 12.8 ng/ml) equal to or better than that reported for these peptides by radioimmunoassay. The assay was highly specific and did not react with a panel of other neuropeptides tested. High level of sensitivity without compromising the specificity was achieved by using activated polyvinyl plates and using purified IgG from high titre rabbit anti-peptide sera. The non specific reaction was minimised by using 10,000 MW cut off amicon filtered supernatants.
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PMID:New, sensitive and specific ELISA for the detection of neuropeptides in culture supernatants. 804 Mar 48

Interactions between growth factor receptor systems may be important in the regulation of cell growth. The proliferation of pancreatic tumor AR42J cells has been shown to be stimulated by Epidermal growth factor (EGF) and gastrin and inhibited by somatostatin. To analyze the interaction between these different peptides, we explored the influence of EGF and gastrin on the somatostatin receptors. Treatment of AR42J cells with 10 nM EGF or gastrin for 24 hr increased specific binding of [125I] Tyr3SMS to 131 and 147% of that in control cells, respectively. The effect of peptides on [125I]Tyr3SMS binding was time- and dose-dependent, with half-maximal effect at 0.2 +/- 0.03 nM EGF and 0.3 +/- 0.15 nM gastrin. Scatchard plots revealed an increase in somatostatin receptor number of 27 and 80% after 48 hr of treatment with EGF and gastrin, respectively, without any change in receptor affinity. The increase in somatostatin receptor density was accompanied by the enhancement of biological responses to somatostatin. In cells pretreated with EGF or gastrin, the potency of somatostatin for inhibiting vasoactive intestinal peptide-stimulated cAMP content was increased 2-fold as that of somatostatin analog, SMS, for inhibiting cell proliferation. Furthermore, the efficiency of SMS as antiproliferative agent was greatly increased. Vasoactive intestinal peptide or forskolin did not modify [125I]Tyr3SMS binding of control or treated cells. The phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) did not affect [125I]Tyr3SMS binding. On the other hand, cycloheximide completely blocked the increase in [125I]Tyr3SMS binding induced by EGF and gastrin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Up-regulation of somatostatin receptors by epidermal growth factor and gastrin in pancreatic cancer cells. 805 63

In mucosa-bearing organs with inherent lymphoid populations, classical modes for control of the immune response may be augmented by products of extrinsic sensory afferent nerve endings which arborize through the lamina propria compartment containing large numbers of T and B lymphocytes. Therefore, we sought to determine the role of neuropeptides (substance P, vasoactive intestinal peptide, and somatostatin) in immune response regulation by using a homogeneous line of T lymphocytes (AO40.1 hybrid), whose activation is driven by a specific Ag (OVA) and where the end point (IL-2 release) could not be contributed to by accessory or other cells. IL-2 was quantitated by the rate of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) metabolism with the use of a murine CD4+ IL-2-dependent T lymphocyte line, and dose-response effects of each neuropeptide were examined over a broad concentration range (10(-14)-10(-6) M) encompassing that regarded as physiologic. Vasoactive intestinal peptide stimulated IL-2 release at low concentrations with a marked effect at 10(-14) M that gradually returned to control levels by 10(-7) M. Somatostatin was associated with a substantial augmentation of AO40.1 T lymphocyte IL-2 release at 10(-10) to 10(-8) M concentrations, whereas substance P demonstrated a stimulatory effect only at high concentrations (10(-9) to 10(-6) M). Concomitant [3H]thymidine uptake studies suggested that changes in cell proliferation or viability did not account for neuropeptide-induced effects in our system. With several exceptions, similar results were found with mitogen (Con A)-stimulated AO40.1 cells and human colonic lamina propria mononuclear cells. It was concluded that the three study neuropeptides, over a broad range of concentrations, have profound stimulatory (and occasionally inhibitory) effects upon the function of a cloned T lymphocyte hybrid cell responding to specific Ag and that these events may reflect those of Ag-driven mucosal T lymphocytes exposed to neuropeptides in vivo.
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PMID:Modulation of T lymphocyte function by neuropeptides. Evidence for their role as local immunoregulatory elements. 851 59

Vasoactive intestinal peptide (VIP) receptors and beta-adrenergic receptors were investigated in rat Harderian gland membranes using 125I-VIP and 125I-cyanopindolol (125I-CYP), respectively, as ligands. The receptor bindings were rapid, reversible, saturable, specific, and dependent on time, temperature, and membrane concentration. The stoichiometric data suggested the presence of two classes of VIP receptors with Kd values of 0.36 and 65.37 nM and binding capacities of 323 and 39,537 fmol VIP/mg protein, respectively. The interaction showed a high degree of specificity, as suggested by competitive displacement experiments with several peptides structurally or not structurally related to VIP as follows: VIP > helodermin > rGRF > PHI > > secretin. Glucagon, somatostatin, insulin, and pancreastatin were ineffective at concentrations up to 1 microM. However, the stoichiometric data suggest the presence of one class of binding sites for 125I-CYP. The Kd for the single site was 290 pM with a binding capacity of 32 pmol/L. The pharmacological characterization of 125I-CYP binding to membranes showed that only isoproterenol, a beta-adrenergic agonist, and norepinephrine, an alpha beta-adrenergic agonist, was as effective as propranolol in inhibiting 125I-CYP binding to Harderian gland membranes. However, alpha 1- and alpha 2-adrenergic agonists and blockers such as methoxamine, prazosin, clonidine, and yohimbine were shown to be ineffective. These results demonstrate the presence of specific VIP and beta-adrenergic receptors in the Harderian gland and suggest a role for VIP and beta-adrenergic agonists in the physiology of this gland.
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PMID:Characterization of binding sites for beta-adrenergic agonists and vasoactive intestinal peptide in the rat harderian gland. 872 8

We recently demonstrated that cultured malignant schwannoma (MS)-derived cells can support human skin mast cell (HSMC) survival in vitro. Cultured HSMCs were spindleshaped in close contract with MS-derived cells, suggesting cell to cell interaction. To elucidate the mechanism of the enhanced HSMC survival in coculture with MS-derived cells and the cellular interactions between HSMC and MS-derived cells, we examined the immunocytochemical characteristics of MS-derived cells using immunofluorescence. Morphologically, cultured MS-derived cells were polygonal with abundant cytoplasm and resembled perineurial cells. The cultured cells immunoreacted positively with vimentin, fibronectin, laminin and collagen IV, but negatively with anti-S100 protein, anti-neuron specific enolase, and anti-neurofilament (68 kd, 145 kd, 200 kd) antibodies. MS-derived cells were distinct from Schwann cells in their lack of S100 protein and also distinguishable from endoneurial fibroblasts that produce fibronectin, but never expressed laminin or collagen IV. MS-derived cells thus possess the characteristics of perineurial cells in their general morphology and their immunocytochemical properties. Immunoreactivity for substance P (SP) and neurokinin A (NKA) was found in the cytoplasm of these cells, particularly around the nuclei. Vasoactive intestinal peptide, somatostatin, and calcitonin gene related peptide were negative. From these findings, we characterized the MS-derived cell's in vitro properties and concluded that it is similar to a perineurial cell. The extracellular matrix protein, laminin, and fibronectin expressed in the MS-derived cell might contribute to HSMC survival and morphology through cell to matrix adhesion. Neuropeptides such as SP and NKA, expressed in the MS-derived cell, might play some role in enhanced HSMC survival in vitro.
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PMID:Immunocytochemical characterization of malignant schwannoma-derived cells in culture. 904 33


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