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)

Activin A stimulated synthesis and secretion of intact FSH in dispersed human FSH-secreting adenoma cells. Significant stimulation was observed after 24 hr. Activin A caused an increase in Ca2+ concentration ([Ca2+]i). This response occurred soon after the activin A action. These effects were blocked in Ca(2+)-deficient medium and by nitrendipine (5 microM). Somatostatin inhibited the activin A-induced intact FSH secretion and the [Ca2+]i response. These findings indicated that Ca2+ influx through voltage-gated Ca2+ channel was involved in the activin A induced synthesis and secretion of intact FSH.
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PMID:Effects of activin A and somatostatin on intact FSH secretion and intracellular Ca2+ concentration in human FSH-secreting pituitary adenoma cells. 134 12

The interaction between somatostatin and activin A was studied in terms of FSH secretion in rat pituitary cells in primary culture. Incubation of pituitary cells with 1 nM activin A for 48 hrs resulted in an increase in FSH release into incubation medium. The effect of activin A was dependent on cell-density and the higher the density, the smaller the stimulatory action of activin A. Somatostatin, by itself, did not affect the FSH secretion. When 100 nM somatostatin was included together with activin A or the cells were pretreated with somatostatin for 2 hrs, the activin A-induced FSH secretion was enhanced. This potentiation effect of somatostatin was inversely dependent on the cell-density. These results indicate that somatostatin enhances, rather than inhibits, the activin A action in pituitary cells.
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PMID:A stimulatory effect of somatostatin: enhancement of activin A-mediated FSH secretion in rat pituitary cells. 256 71

The avian ciliary ganglion contains choroid neurons that innervate choroid vasculature and express somatostatin as well as ciliary neurons that innervate iris/ciliary body but do not express somatostatin. We have previously shown in culture that activin A induces somatostatin immunoreactivity in both neuron populations. We now show in vivo that both targets contain activin A; however, choroid expressed higher levels of activin A mRNA. In contrast, follistatin, an activin A inhibitor, was higher in iris/ciliary body. Iris cell-conditioned medium also contained an activity that inhibited activin A and could be depleted with anti-follistatin antibodies. These results suggest that development of somatostatin is limited to choroid neurons by differential expression of activin A and follistatin in ciliary ganglion targets.
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PMID:Activin A and follistatin expression in developing targets of ciliary ganglion neurons suggests a role in regulating neurotransmitter phenotype. 757 34

We have previously shown that the expression of somatostatin-like immunoreactivity in cultured ciliary ganglion neurons is stimulated by a macromolecule found in choroid cell-conditioned medium (ChCM). Here, we present the following evidence that this somatostatin-stimulating activity (SSA) is activin: human recombinant activin induces somatostatin-like immunoreactivity in CG neurons; ChCM induces hemoglobin synthesis in K562 cells, a biological activity characteristic of activin; activin A-specific antibodies recognize a protein in ChCM; cultured choroid cells contain activin RNA; and SSA is inhibited by follistatin, a specific activin-binding protein. Thus, activin is likely to be a neurodifferentiation factor for CG neurons in vivo.
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PMID:Induction of somatostatin immunoreactivity in cultured ciliary ganglion neurons by activin in choroid cell-conditioned medium. 768 35

The developing avian ciliary ganglion has been a particularly amenable system for the identification, isolation, and characterization of putative target-derived molecules that mediate retrograde interactions. To date a number of biochemically distinct activities that regulate neuronal survival, transmitter phenotype, and chemosensitivity of ciliary ganglion neurons have been identified. Of these, only two survival-promoting molecules have been purified to homogeneity: ciliary neurotrophic factor and a related molecule, growth-promoting activity. A somatostatin-inducing activity found in cultured choroid cells is very likely to be chick activin A. Other molecules that regulate acetylcholine and acetylcholine receptor expression comigrate on a gel filtration column at a molecular weight of 50-60 kD, but they have yet to be isolated. Once molecules that mimic retrograde influences are identified, a number of criteria must be met before their physiological significance can be established. These criteria are (1) availability of the molecule from the target at the appropriate time in development; (2) ability of the neurons to respond to the molecule at the appropriate time in development; (3) demonstration that blocking the activity or availability of the molecule is able to block the target-derived developmental change expressed in the neurons. Of the molecules that are thought to retrogradely influence ciliary neuron development, only growth-promoting activity is known to meet criteria 1 and 2, and experiments are currently underway to test whether inhibition of growth-promoting activity in vivo will exacerbate normal cell death.
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PMID:Target-derived molecules that influence the development of neurons in the avian ciliary ganglion. 791 99

Pancreatic AR42J cells are derived from acinar cells and express both exocrine and neuroendocrine properties. We have recently shown that these cells convert into insulin-producing cells in vitro after treatment with activin A and betacellulin. Here, we investigated the effect of hepatocyte growth factor (HGF) in those cells. When AR42J cells were incubated with HGF, DNA synthesis was attenuated, and the amylase content was reduced in a concentration-dependent manner. HGF-treated cells extended processes, but bundle formation was not observed using an antibody against tubulin. Reverse both insulin and pancreatic polypeptide (PP) were expressed in HGF-treated, but not naive, AR42J cells. Immunocytochemical analysis indicated that approximately 3% of the HGF-treated cells were stained with antiinsulin antibody, and some were also stained with anti-PP antibody. When AR42J cells were exposed to a combination of activin A and HGF, cells extended longer processes, and over 10% of them were stained with antiinsulin antibody. In these cells, messenger RNAs for insulin, PP, glucose transporter 2, and glucokinase, but not those for glucagon or somatostatin, were expressed. A subclone of AR42J cells, AR42J-B13, was obtained. Most of the AR42J-B13 cells converted to insulin-producing cells after the incubation with activin A and HGF. Insulin secretion was augmented by tolbutamide, depolarizing concentrations of potassium, carbachol, and glucagon-like peptide-1 in these cells. These results indicate that HGF reduces the acinar cell-like property of AR42J cells and converts them into insulin-producing cells. The effect of HGF was markedly enhanced by activin A.
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PMID:Formation of insulin-producing cells from pancreatic acinar AR42J cells by hepatocyte growth factor. 875 73

Previous studies have suggested that activin may serve as a neurodifferentiation factor regulating somatostatin expression in neurons of the avian ciliary ganglion (CG). As one aspect of examining the role of activin in CG development, we inquired whether any of the known activin receptors are expressed by developing CG neurons in vivo. In addition, we examined whether activin A mRNA is expressed in the choroid layer and iris of the chicken eye. Oligonucleotide primers were designed for the chicken activin receptor type IIA (cActR-IIA), type IIB (cActR-IIB), and activin A. In reverse-transcription-polymerase chain reaction (rtPCR), an appropriately sized product was amplified from CG cDNA using primers to the cActR-IIA but not the cActR-IIB. Sequencing confirmed the identity of the PCR product as a fragment of the cActR-IIA. It thus appears that mRNA for the type IIA but not the type IIB activin receptor is expressed in the chicken CG. An antisense strand digoxigenin-labeled riboprobe complimentary to a 358-bp portion of the cActR-IIA kinase region hybridized to cells within cryostat sections of embryonic CG. From E6.5-E18, hybridization of this probe appears to be specific for cells with a neuronal morphology. Using rtPCR with activin A-specific primers we detected activin mRNA in the choroid layer of E14 and E19 eyes, and from the iris at E14. Our results are consistent with a role for activin as a neurodifferentiation factor in vivo, and imply that within the CG, the cActR-IIA is specifically expressed by neurons, and that activin A is expressed in the targets of these neurons.
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PMID:Activin receptor mRNA expression by neurons of the avian ciliary ganglion. 898 61

Activin as a neurodifferentiation factor. Our studies of neurotransmitter expression have focused on the expression of neuropeptide transmitters in the avian ciliary ganglion (CG) and have examined the influence of choroidal vascular smooth muscle cells in regulating the differential expression of somatostatin in the CG. In these activities we have identified activin A as a potential target-derived neurodifferentiation factor that can stimulate somatostatin expression in cultured CG neurons. In cultured CG neurons, activin can stimulate the expression of somatostatin in choroid neurons, the pattern of neurotransmitter expression found in vivo, and in the ciliary neurons that would normally not express somatostatin. In vivo, mRNA transcripts of the cActR-IIA appear to be expressed by both choroid and ciliary CG neurons. This suggests that activin might serve as an instructive factor in controlling neuropeptide phenotype. For activin to serve as an instructive factor requires that activin be produced by choroid smooth-muscle target cells. Indeed, activin mRNA and activin-like immunoreactivity are found in choroid cells, in vitro. However, the lack of somatostatin expression by ciliary neurons suggests that activin is not produced by their targets, the iris and ciliary body. This simple view is countered by the observation that activin A mRNA is also present in the iris and activin-like immunoreactivity is detectable in the iris and ciliary body. Instead, the production of the specific activin inhibitor follistatin in the iris and ciliary body is likely to limit the availability of activin to only those neurites innervating the choroid layer, thus accounting for the differential expression of somatostatin in only the choroid CG neurons. This somewhat more complicated arrangement is similar to the mechanism thought to be employed for primary induction during frog embryogenesis. The observations reviewed here are all consistent with the hypothesized role for activin as a molecule whose availability to neurites in the target regulates neurotransmitter expression. Additional in vivo perturbation experiments are needed to further examine this hypothesis; nevertheless, activin appears as a strong candidate for a target-derived neurotransmitter differentiation factor. Activin's potential roles in differentiation: A wide variety of biological effects have been ascribed to activin. Initially identified and purified as a gonadal hormone stimulating the production and release of FSH from the pituitary, activin is also implicated in the stimulation of erythroid differentiation, as a modulator of follicular granulosa cell differentiation, as a mesodermalizing factor in both amphibian and avian early development, and as a component in establishing left-right axial patterning in the chicken embryo. Activin has also been found to be a survival factor for several neuronal cell lines and for rat embryonic neural retina cells in culture. However, activin is not a survival factor for chicken CG neurons in culture. Our observation that activin may play a function in target-derived control of neuropeptide expression adds yet another aspect to the list of its potential biological functions. In addition, activin shares regions of amino acid sequence identity with members of the TGF-beta superfamily, which includes the TGF-betas, Mullerian inhibitory substance, Drosophila decapentaplegic gene product, dorsalin, bone morphogenetic proteins, inhibin, and glial-derived neurotrophic factor. Interestingly, these are all factors that have effects upon cellular differentiation. Effects of activin on other neurons. Activin A--as well as two other TGF-beta superfamily members, BMP-2 and BMP-6--has been shown to induce expression of mRNAs for several neuropeptides in cultured rat sympathetic neurons. In addition, activin A induces ChAT mRNA in cultured sympathetic neurons. (ABSTRACT TRUNCATED)
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PMID:Target tissue influence on somatostatin expression in the avian ciliary ganglion. 916 Sep 73

An important developmental question concerns whether neurotransmitter phenotype is an inherent property of neurons or is influenced by target tissues. This issue can be addressed in the avian ciliary ganglion (CG) which contains two cholinergic populations, ciliary and choroid neurons, that differentially express the peptide cotransmitter, somatostatin. The present study tests the hypothesis that differences in the level of expression of activin A and its endogenous inhibitor follistatin in CG neuron target tissues are responsible for selective expression of somatostatin in choroid neurons. Intraocular injection of activin A or follistatin (300 ng injected at E10/E11) in cultured embryos resulted in a 39% increase or a 23% decrease, respectively, in somatostatin-positive neurons relative to controls. Chorioallantoic membrane application of follistatin (1 microgram daily from E7 to E13) reduced somatostatin positive neurons by 54%. Neuron number, size, and target tissue morphology were unaffected by these treatments. Together with our previous studies, these data suggest that activin A and follistatin are target-derived molecules that regulate neuropeptide phenotype in the ciliary ganglion.
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PMID:Activin A and follistatin influence expression of somatostatin in the ciliary ganglion in vivo. 976 80

AR42J is an exocrine pancreatic cell line that has been reported to differentiate towards an endocrine phenotype when stimulated with various growth factors, such as activin A, hepatocyte growth factor (HGF), betacellulin or glucagon-like peptide 1. In our experiments, AR42J-B13 cells differentiated morphologically in response to the growth factor treatment as reported previously. However, they failed to express the insulin gene. We found that the cells did not express several transcription factors known to be found in the beta-cell, including Nkx6.1, isl-1, Pax4 and Pax6. In addition, the mRNA level for pdx-1 and Nkx2.2 were very low in comparison to the insulinoma cell lines INS-1 and RINm5F. However, some transcription factors typically found in beta-cells and neuroendocrine cells were expressed also in the AR42J-B13 cells. These included BETA2/NeuroD, HNF1alpha, C/EBPbeta and IA-1. Unlike the insulinoma cells, AR42J cells expressed the exocrine transcription factor p48. In order to induce endocrine differentiation, we transfected the AR42J-B13 cells with the full length cDNAs of isl-1, Nkx6.1, Nkx2.2 and pdx-1 under the control of the CMV promoter, both separately and in combinations. The expression of Nkx2.2 led consistently to the appearance of pancreatic polypeptide but not insulin, glucagon or somatostatin mRNA. The PP mRNA expression in Nkx2.2 cDNA transfected cells was independent of the growth factor treatment used for differentiating AR42J cells. In conclusion, the AR42J-B13 line possesses some features of a pancreatic neuroendocrine cell. However, we were unable to confirm the capacity of these cells to differentiate into insulin-producing cells. Our results indicate that Nkx2.2 plays a role in the transcriptional regulation of PP expression.
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PMID:Transcription factor expression and hormone production in pancreatic AR42J cells. 1094 Apr 82


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