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)

Rab3B is involved in the exocytosis of synaptic vesicles and secretory granules in the central nervous system and the anterior pituitary cells. The aim of this study was to elucidate both the role of rab3B in GH secretion and the mutual relationship of rab3B and SNARE proteins. Adult male rats were injected intravenously with 10 microg of growth hormone releasing hormone (GHRH) or 10 microg of somatostatin (SRIF). Untreated rats were used as controls, and their pituitary glands were sectioned for histochemical examination. Rab3B is localized on the limiting membrane of the secretory granules and the cytosol. Confocal laser scanning microscopic observation of immunohistochemical double staining of rab3B and GH revealed that immunoreactivity of rab3B increased in GHRH-treated rats and decreased in SRIF-treated rats. Confocal laser scanning microscopic observation of immunohistochemical double staining of SNAP-25, syntaxin, and rab3B revealed the co-localization of rab3B and these SNARE proteins in GHRH-treated rats, and their dissociation in SRIF-treated rats. These results suggest that rab3B plays a principal role in GH secretion in the anterior pituitary cells and that SNAP-25 and syntaxin act as co-workers with rab3B in the functional regulation of GH secretion.
 ...
PMID:Dynamics of subcellular organelles, growth hormone, Rab3B, SNAP-25, and syntaxin in rat pituitary cells caused by growth hormone releasing hormone and somatostatin. 1450 89

Regulation of SNARE proteins by glucose in pancreatic islets is complex and insufficiently clarified. We aimed to study effects of glucose per se separate from enhancing effects on exocytosis. A 24h culture of rat islets at elevated glucose (27 mmol/L) increased t-SNARES (SNAP-25, syntaxin) (Western blotting). Co-culture with diazoxide, which inhibits glucose-induced insulin secretion, reversed these effects. Effects on SNAP-25 were similar in human and rat islets. Effects of diazoxide were mimicked by blocking secretion with somatostatin (rat islets). Blocking secretion by cooling abolished both glucose and diazoxide effects on SNAP-25. Total SNAP-25 mRNA as well as isoforms alpha and beta were increased by 24-h elevated glucose. Diazoxide failed to reverse the glucose effects on mRNA. However, effects of diazoxide on SNAP-25 protein were nullified by proteasome inhibitors (ALLN, MG-132, and epoxomicin) but not by lysosomal inhibition (NH(4)Cl). Exocytosis per se modifies SNAREs by a process linked to proteasomal activation.
 ...
PMID:Evidence that insulin secretion influences SNAP-25 through proteasomal activation. 1575 69

We have hypothesized that the plasma membrane protein components of the exocytotic soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) complex, syntaxin 1A and SNAP-25, distinctly regulate different voltage-gated K+ (Kv) channels that are differentially distributed. Neuroendocrine islet cells (alpha, beta, delta) uniformly contain both syntaxin 1A and SNAP-25. However, using immunohistochemistry, we show that the different pancreatic islet cells contain distinct dominant Kv channels, including Kv2.1 in beta cells and Kv2.2 in alpha and delta cells, whose interactions with the SNARE proteins would, respectively regulate insulin, glucagon and somatostatin secretion. We therefore examined the regulation by syntaxin 1A and SNAP-25 of these two channels. We have shown that Kv2.1 interacts with syntaxin 1A and SNAP-25 and, based on studies in oocytes, suggested a model of two distinct modes of interaction of syntaxin 1A and the complex syntaxin 1A/SNAP-25 with the C terminus of the channel. Here, we characterized the interactions of syntaxin 1A and SNAP-25 with Kv2.2 which is highly homologous to Kv2.1, except for the C-terminus. Comparative two-electrode voltage clamp analysis in oocytes between Kv2.2 and Kv2.1 shows that Kv2.2 interacts only with syntaxin 1A and, in contrast to Kv2.1, it does not interact with the syntaxin 1A/SNAP-25 complex and hence is not sensitive to the assembly/disassembly state of the complex. The distinct regulation of these closely related channels by SNAREs may be attributed to differences in their C termini. Together with the differential distribution of these channels among islet cells, their distinct regulation suggests that the documented profound down-regulation of islet SNARE levels in diabetes could distort islet cell ion channels and secretory responses in different ways, ultimately contributing to the abnormal glucose homeostasis.
 ...
PMID:Target soluble N-ethylmaleimide-sensitive factor attachment protein receptors (t-SNAREs) differently regulate activation and inactivation gating of Kv2.2 and Kv2.1: Implications on pancreatic islet cell Kv channels. 1675 85

Understanding the trafficking of G-protein-coupled receptors (GPCRs) is of particular importance, especially when modifications of the neurochemic environment occur as in pathological or therapeutic circumstances. In the central nervous system, although some GPCRs were reported to internalize in vivo, little is known about their trafficking downstream of the endocytic event. To address this issue, distribution and expression pattern of the major somatostatin receptor subtype, the somatostatin type 2 (sst2), was monitored in the hippocampus using immunofluorescence, autoradiographic and immunogold experiments from 10 minutes to 7 days after in vivo injection of the receptor agonist octreotide. We then analyzed whether postendocytic trafficking of the receptor was dependent upon integrity of the microtubule network using colchicine-injected animals. Together, our results suggest that upon agonist stimulation, dendritic receptors are retrogradely transported through a microtubule-dependent mechanism to a trans Golgi domain enriched in the t-SNARE syntaxin 6 and trans Golgi network 38 proteins, before recycling. Because we show that the exit rate from the trans Golgi apparatus back to the plasma membrane (hours) is slower than the entry rate (minutes), the neuronal postendocytic trafficking of sst2 receptor is likely to have functional consequences in several neurological diseases in which an increase in somatostatin release occurs.
 ...
PMID:Activated somatostatin type 2 receptors traffic in vivo in central neurons from dendrites to the trans Golgi before recycling. 1752 81

Neuropeptides are signaling molecules that interact with G-protein coupled receptors located both pre- and postsynaptically. Presynaptically, these receptors are localized in axons and terminals away from presynaptic specializations. Neuropeptides are stored in dense core vesicles that are distinct from the clear synaptic vesicles containing classic neurotransmitters such as glutamate and GABA. Because they require a stronger Ca(2+) signal than synaptic vesicles, dense core vesicles do not release neuropeptides with single action potentials but rather require high-frequency trains. Thus, neuropeptides only modulate strongly stimulated synapses, providing negative or positive feedback. Many neuropeptides have been found to inhibit glutamate release from presynaptic terminals, and the major mechanism is likely direct interaction of betagamma G-protein subunits with presynaptic proteins such as SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor). The use of mouse genetic models and specific receptor antagonists are beginning to unravel the function of inhibitory neuropeptides. The opioid receptors kappa and mu, which are activated by endogenous opioid peptides such as dynorphin, enkephalin, and possibly the endomorphins, are important in modulating pain transmission. Dynorphin, nociceptin/orphanin FQ, and somatostatin and its related peptide cortistatin appear to play a role in modulation of learning and memory. Neuropeptide Y has important functions in ingestive behavior and also in entraining circadian rhythms. The existence of neuropeptides greatly expands the computational ability of the brain by providing additional levels of modulation.
 ...
PMID:Presynaptic inhibition of glutamate release by neuropeptides: use-dependent synaptic modification. 1755