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)

The mechanism of periodic gonadotropin-releasing hormone (GnRH) secretion from hypothalamic neurons is difficult to elucidate due to the diffuse distribution of GnRH neurons and the complex interaction of neuronal inputs onto them. Recent use of transgenic techniques allowed construction of an immortalized GnRH neuronal cell line (GT1), which has neuronal markers and secretes GnRH in a periodic fashion. Using the patch-clamp recording technique in the whole-cell and nystatin perforated-patch configuration, the present experiments show that this cell line expressed a tetrodotoxin-sensitive Na channel, two types of Ca channels, three types of outward K channels and a K inward rectifier. The latter current was suppressed in some cells by GnRH or somatostatin. In addition, a gamma-aminobutyric acid (GABA) response, presumably through GABAA receptors, is recorded. In long-term current-clamp recordings, spontaneous depolarizing activity was found to increase, and then decrease, between 20-35 min after removal of the cells from serum- and steroid-containing medium. In some cases, more than one cycle of activity was seen. Under voltage clamp, an inward current was recorded at similar times, with reversal at about -15 mV. Thus, two mechanisms of cell interaction, GABAA responses and feedback through GnRH responses, and one mechanism of endogenous periodic electrical activity were observed in these cells, which could synchronize periodic GnRH release.
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PMID:Ion channel properties and episodic activity in isolated immortalized gonadotropin-releasing hormone (GnRH) neurons. 750 28

Somatostatin enhances an inward rectifier K conductance in cultured locus coeruleus neurons, while substance P reduces an inward rectifier K conductance in cultured nucleus basalis and locus coeruleus neurons. The role of arachidonic acid metabolites in these responses was studied. The somatostatin-induced response was reduced by phospholipase A2 inhibitors, non-specific lipoxygenase inhibitors and specific 5-lipoxygenase inhibitors. A cyclooxygenase inhibitor and a 12-lipoxygenase inhibitor had no effect. 5(S)-HPETE occasionally increased the K conductance, but failed to occlude the somatostatin response. The substance P response was suppressed by a 5-lipoxygenase inhibitor but not by a 12-lipoxygenase inhibitor. These results suggest that the 5-lipoxygenase pathway is not a specific messenger of either one of these responses, but that it plays a more general role in maintaining or enhancing the effectiveness of both somatostatin and substance P responses.
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PMID:The role of arachidonic acid metabolism in somatostatin and substance P effects on inward rectifier K conductance in rat brain neurons. 753 42

In locus coeruleus neurons, substance P (SP) suppresses an inwardly rectifying K+ current via a pertussis toxin-insensitive guanine nucleotide binding protein (G protein; GnonPTX), whereas somatostatin (SOM) or [Met]enkephalin (MENK) enhances it via a pertussis toxin-sensitive G protein (GPTX). The interaction of the SP and the SOM (or MENK) effects was studied in cultured locus coeruleus neurons. In neurons loaded with guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]), application of SOM (or MENK) evoked a persistent increase in the inward rectifier K+ conductance. A subsequent application of SP suppressed this conductance to a level less than that before the SOM (or MENK) application; the final conductance level was independent of the magnitude of the SOM (or MENK) response. This suppression by SP was persistent, and a subsequent SOM (or MENK) application did not reverse it. When SP was applied to GTP[gamma S]-loaded cells first, subsequent SOM elicited only a small response. In GTP-loaded neurons, application of SP temporarily suppressed the subsequent SOM- (or MENK)-induced conductance increase. These results suggest that the same inward rectifier molecule that responds to an opening signal from GPTX also responds to a closing signal from GnonPTX. The closing signal is stronger than the opening signal.
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PMID:Opposing mechanisms of regulation of a G-protein-coupled inward rectifier K+ channel in rat brain neurons. 753 96

In GH3/B6 cells at least two different inward K+ currents are observed that are regulated by thyrotropin-releasing hormone and somatostatin, respectively. Using a polymerase chain reaction based approach a cDNA was isolated and functionally expressed in human embryonic kidney cells that encodes an inward rectifier K+ channel, rIRK3, with a predicted molecular mass of 49.7 kDa. Corresponding transcripts of 2.6 kb have been detected in rat brain, pituitary and GH3/B6 cells. In situ hybridization revealed that rIRK3 mRNA is distributed throughout the brain and occurs predominantly in the piriform cortex, indusium griseum, supraoptic nucleus, facial nucleus and cerebellar Purkinje cells.
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PMID:Cloning, functional expression and mRNA distribution of an inwardly rectifying potassium channel protein. 779 7

In cultured noradrenergic neurons from the rat locus coeruleus, application of recombinant G protein beta 1 gamma 2 subunits (30 nM) to the cytoplasmic side induced single channel activity similar to the somatostatin-induced single channel activity of G protein-coupled inward rectifier potassium channels (Kir (G)). In contrast, recombinant GTP gamma S-activated, myristoylated alpha i2 (100 nM) did not activate this brain Kir (G). Application of beta 1 gamma 2 C68S (30 nM or 150 nM), in which the cysteine residue fourth from the carboxyl terminus of gamma 2 was replaced by serine, failed to activate the brain Kir(G). This mutant lacks prenylation which is required for the association of beta gamma subunit with the cell membrane. Thus, our results suggest that the association of beta gamma subunit with the cell membrane is a prerequisite for activating Kir(G) channels.
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PMID:Activation of G protein-coupled inward rectifier K+ channels in brain neurons requires association of G protein beta gamma subunits with cell membrane. 870 63

The recent cloning of five somatostatin receptors has made it possible to begin screening for selective ligands in order to begin characterization of these receptor subtypes expressed endogenously. We have recently reported the characterization of ligands selective for SSTR2 and SSTR5 [Raynor K. et al. (1993) Molec. Pharmac. 43, 838-844; 44, 385-392]. Both of these somatostatin receptor subtypes are endogenously expressed in the mouse pituitary cell line AtT-20 [O'Carroll A.-M. et al. (1992) Molec. Pharmac. 42, 939-946; Patel Y. C. et al. (1994) J. biol. Chem. 269, 1506-1509; Tallent M. et al. (1996) Neuroscience 71, 1073-1081]. Using these selective ligands, as well as other somatostatin analogs, we have characterized the somatostatin receptor which couples to the inward rectifier K+ current in AtT-20 cells. This receptor is sensitive to hexapeptide analogs of somatostatin, but insensitive to octapeptide analogs. This pharmacological profile is distinct from any of the cloned somatostatin receptors and therefore may represent a novel receptor. Somatostatin has been shown to potentiate an inward rectifying K+ channel in many different types of neuronal and non-neuronal cells. The activation of this current is thought to be an important mechanism by which somatostatin inhibits neuronal firing and decreases neurotransmitter and hormone release [Mihara S. et al. (1987) J. Physiol. 390, 335-355]. Therefore, the novel somatostatin receptor coupling to the inward rectifier in AtT-20 cells may be important in somatostatin's role in regulating neurotransmission and hormone release.
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PMID:Evidence that a novel somatostatin receptor couples to an inward rectifier potassium current in AtT-20 cells. 880 4

1. In cultured rat locus coeruleus neurons, somatostatin or met-enkephalin induces an inwardly rectifying K+ conductance. This inward rectifier was analyzed at the single-channel level. 2. Using the inside-out patch-clamp, guanosine 5'-triphosphate (GTP) application to the cytoplasmic side in the presence of somatostatin or met-enkephalin in the pipette produced a large increase in channel activity, which disappeared on switching from GTP to guanosine 5'-diphosphate. 3. The unitary conductance was approximately 30 pS at -95 mV with an extracellular K+ concentration of 156 mM and an intracellular K+ concentration of 124 mM at 23 degrees C. The channel showed burst behavior, and the closed time histogram was fit by two exponentials, with the fast time constant being 0.4 ms. The burst time histogram was also fit by two exponentials, with time constants of 0.24 and 2.0 ms (at 10 nM somatostatin). When the somatostatin concentration was changed from 500 to 1 nM, the kinetic behavior of the channel did not change, except that the open probability of the patch was decreased. 4. The current-voltage relation of the unitary channel current showed inward rectification. The reversal potential coincided with the K+ equilibrium potential, and it shifted according to a change in the K+ equilibrium potential. 5. In the presence of external somatostatin, the application of guanosine 5'-O-(3-thiotriphosphate) to the cytoplasmic side induced an irreversible activation of this channel. 6. These results indicate that this K+ channel is the microscopic counterpart of the somatostatin- or met-enkephalin-induced inwardly rectifying K+ current in whole cell recording, and that the channel is activated by a G protein without a diffusible second messenger. Thus this channel is identified as a neuronal G-protein-coupled inward rectifier K+ channel. 7. Analysis of the burst behavior, based on a close-close-open kinetic model, revealed that there are at least four states in the K+ channel, a short gap, a longer closing, a short opening, and a long opening, and that the neuronal inward rectifier is activated at faster rates than the atrial inward rectifier.
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PMID:Single-channel properties of a G-protein-coupled inward rectifier potassium channel in brain neurons. 882 60

Muscarine and somatostatin enhance an inward rectifier K+ conductance in the AtT-20 pituitary cell line. Both effects are abolished by pertussis toxin (PTX). To determine which PTX-sensitive G protein mediates these agonist effects, we made cDNAs encoding mutant PTX-insensitive Gi alpha subtypes, in which the cysteine residue fourth from the C terminus was replaced with serine. The mutated cDNA was transfected into AtT-20 cells, resulting in stable cell lines overexpressing a Gi alpha subtype. As controls, wild-type Gi alpha cDNA was transfected into AtT-20 cells. The agonist-induced increase of the inward rectifier K+ conductance in the transfectants was examined with the whole-cell clamp method. Only in the cell lines into which the mutated (PTX-insensitive) Gi2 alpha cDNA was transfected, did the muscarine response become PTX-insensitive, suggesting that Gi2 couples to the muscarinic receptor and enhances the activity of the inward rectifier K+ channel. However, PTX-insensitive somatostatin responses were not obtained in any of the cell lines transfected with a mutated Gi alpha cDNA, suggesting either that none of the Gi subtypes is a transducer for the somatostatin effect or that the mutation prevents the coupling of the Gi alpha to the somatostatin receptor.
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PMID:G protein specificity of the muscarine-induced increase in an inward rectifier potassium current in AtT-20 cells. 912 37

1. Types of G proteins (G protein alpha-subunit subtypes) which mediate the activation of inward rectifier K+ currents by somatostatin (somatotrophin release-inhibiting factor, SRIF) were determined in cultured locus coeruleus neurones from newborn rats and in AtT-20 cells (a mouse pituitary cell line). 2. The whole-cell patch clamp technique was used together with injection of antibodies against pertussis toxin (PTX)-sensitive G protein alpha-subunits or with injection of antisense (or sense) oligonucleotides against these G proteins. 3. In locus coeruleus neurones, the SRIF-induced activation of inward rectifier K+ currents was inhibited by anti-G alpha i1/G alpha i2 antibody injection, but not by anti-G alpha i3 or by anti-G alpha o/G alpha i3 antibody injection, suggesting that the SRIF response is mediated through G alpha i1 and/or G alpha i2. 4. The SRIF-induced activation of the inward rectifier was suppressed in locus coeruleus neurones after injection of antisense oligonucleotides against G alpha i2, but not by injection of sense oligonucleotides against G alpha i2. Injection of antisense (or sense) oligonucleotides against G alpha i1, G alpha i3 and G alpha O (common) had no effect. These results suggest that G alpha i2 is involved in this SRIF response. 5. In AtT-20 cells, the SRIF-induced activation of inward rectifier K+ currents was suppressed by injection of anti-G alpha i3 antibody, but not by injection of anti-G alpha i1/G alpha i2 antibody. 6. The above results indicate that Gi mediates the SRIF effects on inward rectifier K+ currents. However, different subtypes of Gi are involved in the brain neurones and in the endocrine cells: Gi2 in locus coeruleus neurones and Gi3 in AtT-20 cells.
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PMID:Different G proteins mediate somatostatin-induced inward rectifier K+ currents in murine brain and endocrine cells. 927 8

Kir6.2, a member of the inward rectifier K+ channel family, is a component of the ATP-sensitive K+ (K[ATP]) channel considered to play a key role in glucose-induced insulin secretion. We studied the distribution of Kir6.2 in mouse pancreas at the cellular level. The sites of Kir6.2 mRNA expression were determined by in situ hybridization histochemistry with a digoxigenin (DIG)-labeled antisense cRNA probe. The hybridization signal was unevenly present throughout the islets of Langerhans, while no distinct signal was detected in exocrine acinar cells. This distribution was confirmed by another cRNA probe complementary to a different region of Kir6.2 mRNA. In situ hybridization and immunofluorescence staining of serial sections with the anti-insulin, the anti-glucagon, and the anti-somatostatin antibodies showed Kir6.2 mRNA to be present in alpha-, beta-, and delta-cells. Furthermore, immunofluorescence staining with antibody raised against Kir6.2 revealed that Kir6.2 protein is localized within the pancreatic islets and is not found in exocrine pancreas. Kir6.2 was further shown to be located together with insulin, glucagon, or somatostatin. The positive staining of Kir6.2 appeared concentrated along the contour of each islet cell, suggesting that Kir6.2 is at the plasma membrane of islet cells. These results suggest that Kir6.2, as a component of K(ATP) channels, is an important molecule in the regulation of all the release of insulin, glucagon, and somatostatin.
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PMID:Localization of the ATP-sensitive K+ channel subunit Kir6.2 in mouse pancreas. 928 44


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