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)

1. Vasoactive intestinal polypeptide (VIP) is present in high concentrations in the hypothalamus and appears to be involved in the modulation of growth hormone (GH) secretion. The effects of VIP on hypothalamic somatostatin (SMS) release are, however, controversial. 2. To further elucidate the mechanism of action of this peptide on GH secretion we studied the effects of VIP on SMS secretion from incubated rat hypothalamic fragments in vitro. 3. At 10(-6) M, VIP induced a significant increase in basal SMS release (P less than 0.01), whereas at 10(-10) M it had an inhibitory effect. 4. We suggest that the increase in GH after in vivo administration of VIP may be modulated, at least in part, by a direct effect of this peptide on SMS neurons, while the stimulatory effect of high doses of VIP on SMS release may represent a pharmacological interaction of this peptide with growth hormone releasing hormone, peptide histidine isoleucine, or glucagon receptors.
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PMID:Dose-dependent effects of vasoactive intestinal polypeptide on somatostatin release from hypothalamic fragments in vitro. 257 24

The paraventricular nucleus (PVN) of male albino rats was analyzed for the presence of glucocorticoid receptor-like immunoreactivity (GR-LI) in neuropeptide containing neurons. Using immunohistochemistry, coronal sections trough the entire PVN were double-stained with a mouse monoclonal antibody against GR and one of the following antisera: rabbit antiserum to corticotropin releasing factor (CRF), neurotensin (NT), enkephalin (ENK), cholecystokinin (CCK), thyrotropin releasing hormone (TRH), galanin (GAL), peptide histidine isoleucine (PHI), vasoactive intestinal polypeptide (VIP), somatostatin (SOM) or tyrosine hydroxylase (TH). For comparison the occurrence of GR-LI in NT-, SOM-, NPY- or TH-positive neurons of the arcuate nucleus was also studied. Our results indicate that GR-LI is present in the parvocellular part of the PVN but not in its magnocellular portion. Virtually every parvocellular neuron in the PVN containing one of the above mentioned peptides was also positive for GR, with the exception of SOM neurons, of which only about two thirds showed detectable levels of GR-LI. All TH-positive, presumably dopamine neurons in the PVN were GR-positive. In the arcuate nucleus all TH- and NPY-positive neurons as well as a large proportion of the SOM- and NT-immunoreactive neurons contained GR-LI. The results indicate that in the PVN, in addition to the CRF neurons, certain peptidergic neurons in the parvocellular part of the PVN, without any established role in the control of ACTH synthesis and release, may also be under glucocorticoid control. This seems to be the case also for most arcuate neurons.
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PMID:Coexistence of glucocorticoid receptor-like immunoreactivity with neuropeptides in the hypothalamic paraventricular nucleus. 259 16

Several non-opioid regulatory peptides have been described in normal human skin localized both in neural fibres and in cellular elements. These include substance P, neurokinin A, neurotensin, calcitonin gene-related peptide, vasoactive intestinal polypeptide, peptide histidine methionine, neuropeptide Y, somatostatin, galanin and atrial natriuretic peptide. In the present review the morphological aspects and distribution of peptidergic nerves in normal human skin are presented. The main functional roles on nociception, pruritus, cutaneous blood flow and sweat production are discussed in regard to neuropeptides. The relationships between neuropeptides, mast-cells and neurogenic inflammation are discussed in detail. Pathological conditions are reported in which an alteration in the peptidergic control might be of importance in their pathogenesis. Some working hypothesis are discussed.
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PMID:[Neuropeptides and the skin: morphological, functional and physiopathological aspects]. 268 Sep 14

The occurrence and distribution of peptide-containing nerve fibers to the cerebral circulation are described. Immunocytochemical studies have revealed that cerebral blood vessels are invested with nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP). In addition, there are studies reporting the occurrence of putative neurotransmitters such as cholecystokinin, dynorphin B, galanin, gastrin releasing peptide, vasopressin, neurotensin, and somatostatin. The nerves occur as a longitudinally oriented network around large cerebral arteries. There is often a richer supply of nerve fibers around arteries than veins. The origin of these nerve fibers has been studied by retrograde tracing and denervation experiments. These techniques, in combination with immunocytochemistry, have revealed a rather extensive innervation pattern. Several ganglia, such as the superior cervical ganglion, the sphenopalatine ganglion, the otic ganglion, and small local ganglia at the base of the skull, contribute to the innervation. Sensory fibers seem to derive from the trigeminal ganglion, the jugular-nodose ganglionic complex, and from dorsal root ganglia at level C2. The noradrenergic and most of the NPY fibers derive from the superior cervical ganglion. A minor population of the NPY-containing fibers contains VIP instead of NA and emanates from the sphenopalatine ganglion. The cholinergic and the VIP-containing fibers derive from the sphenopalatine ganglion, the otic ganglion, and from small local ganglia at the base of the skull. Most of the SP-, NKA-, and CGRP-containing fibers derive from the trigeminal ganglion. Minor contributions may emanate from the jugular-nodose ganglionic complex and from the spinal dorsal root ganglia. NPY is a potent vasoconstrictor in vitro and in situ. VIP, PHI, SP, NKA, and CGRP act via different mechanisms to induce cerebrovascular dilatation. The sympathetic, the parasympathetic, and the sensory systems appear to be involved in modulating cerebrovascular tone in hypertension and in conditions of threatening vasoconstriction, e.g., subarachnoid hemorrhage and migraine.
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PMID:Neuropeptides in the cerebral circulation. 270 77

High-performance liquid chromatography-purified 125I-vasoactive intestinal peptide (VIP) bound to T-47D human breast cancer cells in a specific, saturable, and reversible manner. Scatchard plots were compatible with the presence of one class of VIP receptors with high affinity (Kd = 4.5 X 10(-10) M VIP, and Bmax = 293 fmol/mg protein). The neuropeptide and its natural analogues inhibited the binding of 125I-VIP and stimulated cyclic AMP (cAMP) generation in T-47D cells 96-fold (EC50 = 7 X 10(-10) M VIP), in the following order of potency: VIP greater than helodermin greater than human peptide with N-terminal histidine and C-terminal methionine greater than human pancreatic growth hormone-releasing factor greater than human secretin. In contrast, 125I-VIP binding was not displaced by pancreatic glucagon, human oxyntomodulin, truncated glucagon-like peptide-1, glucagon-like peptide-2, the somatostatin analogue SMS 201-995, gastric inhibitory peptide, and a series of steroid hormones or peptides unrelated to VIP. VIP also increased cAMP generation in seven other human breast cancer cell lines: H4-66B, HSL 53, HSL 78, MCF 7, MDA-MB231, T-47D2, and ZR75-1. Adenylate cyclase activity rose from 72.2 +/- 14 to 1069 +/- 66 pmol cAMP/min mg protein after the addition of 10(-7) M VIP to T-47D plasma membranes. In agreement with our pharmacological results and the Scatchard analysis of the binding data, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the solubilized receptor in the T-47D membranes permitted identification of one autoradiographic band with a molecular weight of 69,000. The sensitivity of the Mr 69,000 binding site to GTP and low doses of VIP implies that in T-47D cells, this component constitutes the membrane domain involved in the functional regulation of adenylate cyclase by VIP receptors. Our results indicate a role for the VIP receptor-cAMP system in human breast cancer cells.
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PMID:Pharmacology, molecular identification and functional characteristics of vasoactive intestinal peptide receptors in human breast cancer cells. 284 44

To determine the effect of vasoactive intestinal peptide (VIP) on the secretion of somatostatin by neurons, dispersed fetal cerebral cortical and diencephalic cells grown in culture were exposed on day 10 or 11 of culture to various concentrations of VIP, and for comparison to the structurally related peptides PHI (Peptide Histidine Isoleucine-27), growth hormone (GRH1-44-NH2) and secretin and to cholecystokinin. VIP elicited a dose-dependent release of somatostatin from both cortical and diencephalic cells, the lowest effective concentration being 6 X 10(-9) M. PHI also brought about release of somatostatin, but was between 0.06 and 0.1 times as potent as VIP. Placed together in a concentration of 10(-7) M, the two peptides did not have an additive effect. In this system GRH1-44-NH2, secretin and CCK octapeptide were without effect.
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PMID:Vasoactive intestinal peptide and PHI stimulate somatostatin release from rat cerebral cortical and diencephalic cells in dispersed cell culture. 286 Sep 51

The characterization of GH-releasing peptides in vivo has been complicated by the effects of endogenous hypothalamic regulation of GH secretion. We describe a model to minimize endogenous hypothalamic interference by pretreating adult male rats with iv diethyldithiocarbamate and antisomatostatin serum. This pretreatment regimen established stable, detectable basal levels of plasma GH and eliminated spontaneous GH pulses for 12 h. Repeated pulsatile administration of 400 ng/kg iv rat hypothalamic GH-releasing factor (rGRF) produced consistent GH responses. Linear, nearly identical, dose responses (from 300-5000 ng/kg) were observed with rGRF and human pancreatic GH-releasing factor (GRF44) with ED50 values of 1059.3 and 1116.9 ng/kg, respectively. We also investigated a synthetic hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP), which was previously reported to have potent GH-releasing activity. In contrast to either rGRF or GRF44, repeated administration of the same dose of GHRP did not produce consistent GH responses. The first bolus of GHRP produced a larger GH pulse than the second (P less than 0.01), followed by increasing GH responses from injections 2 to 7. GHRP was about 2 log orders less potent than either rGRF or GRF44 on a molar basis. The disparity between the native peptides and GHRP suggests that the synthetic peptide may act to release GH through a different mechanism(s). In summary, these data indicate that the diethyldithiocarbamate/anti-somatostatin serum-treated animal may be a useful model for investigating the pituitary actions of GH-releasing peptides.
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PMID:Dose-response characteristics of various peptides with growth hormone-releasing activity in the unanesthetized male rat. 286 Oct 83

Previous studies have shown that intracisternal (i.c.), but not intravenous administration of thyrotropin-releasing hormone (TRH), an endogenous tripeptide (pGlu-His-Pro-NH2), produces a time-, dose-dependent and vagus-mediated stimulation of acid secretion in rats. This study was designed to test the hypothesis that endogenous brain TRH plays a role in regulation of acid secretion in the pylorus-ligation model. In confirmation of previous reports, i.c. TRH (1 microgram) significantly (P less than 0.01) stimulated gastric acid output, gastric secretory volume and decreased gastric intraluminal pH. Intracerebroventricular (i.c.v.) infusion of TRH antiserum (anti-TRH) 30 min prior to pyloric occlusion significantly reduced acid output, secretory volume and raised gastric pH. This inhibitory gastric acid secretory response to i.c.v. anti-TRH appears to be specific since i.c.v. infusion of normal rabbit serum or antisera raised against neurotensin (NT), Leu-enkephalin (L-enk), gonadotropin-releasing hormone (GnRH), somatostatin (SRIF) and alpha-melanocyte stimulating hormone (alpha-MSH) were without measurable effect. The findings of this study indicate that endogenous brain TRH, but not NT, L-enk, GnRH, SRIF or alpha-MSH plays a physiological role in regulation of acid secretion.
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PMID:Inhibition of gastric acid secretion by immunoneutralization of endogenous brain thyrotropin-releasing hormone. 288 Jun 45

Cyclic hexapeptide analogs of somatostatin with insulin, glucagon, and growth hormone (GH) release inhibitory potencies of 50-200 times those of somatostatin have been synthesized. Replacement of the Phe-7 residue with histidine has resulted in increased oral bioavailability and duration of action. Metabolic degradation of L-Trp containing analogs upon oral administration has also been overcome by incorporation of histidine. The all L-amino acid containing analog cyclo(NMePhe-His-Trp-Lys-Val-Ala) shows oral bioavailability comparable to D-Trp containing analogs.
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PMID:Somatostatin analogs with improved oral bioavailability. 288 53

We describe a 63-yr-old man with disseminated medullary carcinoma of the thyroid and pancreatic nesidioblastosis and microadenosis with pancreatic polypeptide (PP) hypersecretion. His major symptoms were watery diarrhea, flushing, and abdominal bloating; these and the elevated plasma PP levels did not change after resection of the distal two thirds of the pancreas, which contained a 2-cm mass of nesidioblastotic tissue. Postoperatively, a long-acting somatostatin analog, SMS 201-995 (100 micrograms/day), normalized PP secretion acutely and chronically (7 months) and ameliorated his symptoms. The analog had no side-effects and did not alter glucose tolerance, calcitonin hypersecretion, or growth of the medullary carcinoma, but it did inhibit GH secretion. After withdrawal from therapy for 1 month, PP hypersecretion and all symptoms except diarrhea recurred. The coexistence of medullary carcinoma of the thyroid and PP cell nesidioblastosis represents a new variant of the overlap syndromes between multiple endocrine neoplasia types I and II. Patients with medullary carcinoma and unexplained watery diarrhea should have fasting gastroenteropancreatic hormone assays done to screen for a potential gastrointestinal or pancreatic origin for the diarrhea.
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PMID:Medullary carcinoma of the thyroid, pancreatic nesidioblastosis and microadenosis, and pancreatic polypeptide hypersecretion: a new association and clinical and hormonal responses to long-acting somatostatin analog SMS 201-995. 288 96


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