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. Human skin mast cells, unlike other human mast cells so far studied, released histamine in a concentration-related manner in response to substance P, vasoactive intestinal peptide (VIP) and somatostatin (1 microM to 30 microM). In contrast, eledoisin, physalaemin, neurokinin A, neurokinin B, calcitonin gene-related peptide (CGRP), neurotensin, bradykinin and Lys-bradykinin induced negligible histamine release. 2. The low histamine releasing activity of physalaemin, eledoisin, neurokinin A and neurokinin B relative to substance P suggests that the human skin mast cell activation site is distinct from the tachykinin NK-1, NK-2 or NK-3 receptors described in smooth muscle. 3. The relative potencies of substance P and its fragments SP2-11, SP3-11, SP4-11 and SP1-4 in releasing histamine from human skin mast cells suggests that both the basic N-terminal amino acids and the lipophilic C-terminal portion of substance P are essential for activity. 4. Peptide-induced histamine release, like that induced by compound 48/80, morphine and poly-L-lysine, is rapid, reaching completion in 10-20 s, is largely independent of extracellular calcium but requires intact glycolysis and oxidative phosphorylation. 5. The substance P analogue, [D-Pro4,D-Trp7,9,10] SP4-11 (SPA), not only reduced substance P-induced histamine release in a concentration-related manner but also inhibited that induced by VIP, somatostatin, compound 48/80, poly-L-lysine and morphine but not anti-IgE. 6. The similar characteristics of histamine release induced by substance P, VIP, somatostatin, compound 48/80, poly-L-lysine and morphine suggest that they share a common pathway of activation-secretion coupling distinct from that of IgE-dependent activation. Furthermore, the ability of human skin mast cells to respond to basic non-immunological stimuli including neuropeptides may reflect a specialised function for these cells.
 ...
PMID:Characterization of neuropeptide-induced histamine release from human dispersed skin mast cells. 246 82

Mast cells of human skin, but not lung, adenoids, tonsils, or intestine, release histamine in response to substance P, vasoactive intestinal polypeptide, and somatostatin. The substance P receptor of skin mast cells is not of the NK-1, NK-2 or NK-3 subtypes of smooth muscle. Time course and calcium dependency of release by peptides differed from anti-IgE. With anti-IgE, the molar ratios of histamine:PGD2:LTC4 generated by skin mast cells was 1,000:25:2, whereas with substance P these ratios were 1,000:1:0.1. Similar results were obtained with the other neuropeptides. The ability of peptides to stimulate skin mast cell histamine release suggests a mechanism whereby their release from dermal nerve endings is coupled to changes in microvasculature.
 ...
PMID:Interaction of neuropeptides with human mast cells. 246 22

The antagonistic effect of newly synthesized substance P (SP) analogues containing D-histidine was examined on behavioural responses induced in mice by SP, neurokinin (NK) A, physalaemin, eledoisin, somatostatin and bombesin. [D-Pro2,D-Trp7,9]SP (DPDT-SP) and [D-Arg1,D-Trp7,9,Leu11]SP (spantide) were used as references for comparison. When co-administered with SP intrathecally, all the SP analogues used decreased the SP-induced response which consists of scratching, biting and licking. DPDT-SP and spantide attenuated non-specifically the SP-like behavioural responses induced by physalaemin, eledoisin, NK A and somatostatin. In general, the introduction of D-histidine in position 9 of the SP molecule resulted in potent antagonistic activity of the SP derivative on the behavioural responses to SP. Of these SP analogues, [D-Arg1,D-Pro2,4,D-Phe7,D-His9]SP attenuated selectively the behavioural responses produced by NK-1 receptor agonists such as SP and physalaemin. Simultaneous injection of [D-Phe7,D-His9]SP-(6-11) selectively inhibited the SP-induced behavioural response without affecting the other peptide-induced behavioral response. The results suggest that the behavioural antagonism induced by [D-Arg1,D-Pro2,4,D-Phe7,D-His9]SP and [D-Phe7,D-His9]SP-(6-11) is probably due to the specific blockade of spinal NK-1 receptors.
 ...
PMID:Substance P analogues containing D-histidine antagonize the behavioural effects of intrathecally co-administered substance P in mice. 248 48

Neurokinin A and B are present in neurons situated in lung and NK-1 receptors have been described on tracheal submucosal gland cells. In the present study we compared the ability of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) to stimulate airway mucus secretion. Furthermore, we characterized the interaction of NKA and NKB with galanin and somatostatin. The rank order of the tachykinins to stimulate airway mucus secretion was SP > NKA > NKB suggesting that NK-1 receptors mediate these effects(EC50:SP: 50 nmol/l, NKA: 200 nmol/l, NKB: 400 nmol/l). Galanin and somatostatin were equally potent to inhibit NK-A and NK-B stimulated airway mucus release. These results suggest that NK-A and NK-B are potent stimulators of airway macromolecule secretion. Galanin and somatostatin potently inhibit these actions of the tachykinins. Therefore, airway mucus secretion is controlled by a complex network of several different mediators.
 ...
PMID:Galanin and somatostatin inhibition of neurokinin A and B induced airway mucus secretion in the rat. 754 Nov 2

In murine Schistosomiasis mansoni, granuloma eosinophils make SP. We investigated whether SP affects lymphokine secretion in murine schistosomiasis. SP at > or = 10(-10) M, and other tachykinins at much higher concentrations, substantially increased IFN-gamma secretion from spleen or granuloma inflammatory cells primed in vitro by suboptimal stimulatory concentrations of egg Ag or mitogen. Cells receiving maximal antigenic or mitogenic stimulation were affected marginally. Also, tachykinins induced no IFN-gamma from resting cells receiving no Ag or mitogen stimulation. There are three distinct tachykinin receptors, called NK-1, NK-2 and NK-3. SP binds the NK-1 receptor with highest affinity. Specific NK-1 receptor antagonists blocked all tachykinin-induced, IFN-gamma secretion. An NK-2 receptor inhibitor had no effect. Thus, SP and other tachykinins were acting through an NK-1 receptor. Inflammatory cells from 4-day-old granulomas cultured in vitro secrete IFN-gamma. Yet, there was no measurable IFN-gamma when SP receptor antagonists were added to the cultures. Moreover, animals treated in vivo with the NK-1 receptor antagonist CP-96,345 produced smaller granulomas. This suggested that endogenous SP may be necessary for normal induction of granuloma IFN-gamma secretion and a normal granulomatous response. Granuloma macrophages make somatostatin (SOM) that can decrease IFN-gamma secretion. Yet, IFN-gamma secretion was unaffected when both SP and SOM were in the cell cultures. In conclusion, SP modulates Ag-driven IFN-gamma secretion through a NK-1 receptor. Also, SP and SOM may be components of a natural circuit within inflammation that regulates IFN-gamma production.
 ...
PMID:Substance P modulates antigen-induced, IFN-gamma production in murine Schistosomiasis mansoni. 768 34

A rare insulin-immunoreactive neuroendocrine tumor of the duodenum in a 54 year old male is reported. The incidentally identified tumor was located on the anterior free wall of the duodenal bulb and measured approximately 6 mm in diameter. Uncomplicated endoscopic resection of the tumor was carried out. The lesion exhibited classic histologic features of insulinoma of the beta-islet cell type with stromal amyloid deposition. In addition to positive reactivities of chromogranin A, neuron-specific enolase, synaptophysin, Leu 7 (CD57), cystatin C, CA15-3 and cytokeratin, the non-argyrophilic tumor cells were strongly immunoreactive for insulin and C-peptide. The stromal amyloid was clearly labeled for amylin. A few cells were stained for somatostatin, whereas other hormones were negative. Interestingly, a few isolated insulin-positive cells were identified in the non-neoplastic duodenal mucosa in the proximity of the tumor. Immunoelectron microscopy using paraffin sections disclosed insulin-immunoreactive secretory granules in the cytoplasm. The patient exhibited no signs or symptoms of hypoglycemia. Serum insulin levels were not measured prior to resection. No tumors were demonstrated in the pancreas. Magnetic resonance imaging revealed a 1 cm asymptomatic pituitary mass, in association with moderately elevated serum prolactin levels. The patient is currently being followed up in the outpatient clinic.
 ...
PMID:Aberrant insulinoma of the duodenal bulb. 858 Nov 56

Intrathecal (i.t.) administration of morphine in the spinal subarachnoid space of mice produced a severe hindlimb scratching followed by biting and licking. The onset of the scratching behaviour was observed 60-70 s after i.t. injection of morphine (60 and 90 nmol), and had a duration of 3-4 min. The morphine-induced behaviour was increased additively by i.t. co-administration of substance P (SP). This characteristic behavioural response was inhibited dose-dependently by i.t. co-administration of the tachykinin NK-1 receptor antagonists, sendide and CP-96,345. Significant antagonistic effects of SP (1-7), a putative antagonist for NK-1 receptors and [D-Phe7, D-His9]SP (6-11), a selective antagonist for SP receptors, were observed against the morphine-induced behaviour. Pretreatment with i.t. SP antiserum and i.t. capsaicin resulted in reduction of the response to morphine. I.t. administration of somatostatin (SOM) antiserum, cysteamine, a relatively selective depletor of SOM and cyclo-SOM, a SOM receptor antagonist, produced no inhibitory effect on the morphine-induced behaviour. These results demonstrate that a spinal system of neurones containing SP may be involved in elicitation of the behavioural episode following i.t. injection of morphine in mice.
 ...
PMID:Spinally-mediated behavioural responses evoked by intrathecal high-dose morphine: possible involvement of substance P in the mouse spinal cord. 882 71

The effects of infusion of the two tachykinins, substance P (SP) and neurokinin A (NKA), and of capsaicin on the release of glucagon-like peptide-1 (GLP-1), somatostatin, and vasoactive intestinal polypeptide (VIP) were studied in isolated, vascularly perfused ileal segments. SP (10(-8) M) stimulated GLP-1, somatostatin, and VIP release to 141.8+/-6.6% (N = 18), 230.3+/-38.7% (N = 21), and 359.7+/-60.5% (N = 22) of basal output, respectively. NKA (10(-8) M) only stimulated VIP release (to 181.2+/-16.7% of basal release, N = 22). The effects of SP and NKA were blocked by the NK-1 receptor antagonist CP96345 (10(-6) M). Infusion of atropine (10(-6) M) had no effect on the SP-induced GLP-1 release, but partly inhibited the effect of SP on somatostatin and VIP release, and the effect of NKA on VIP release. Capsaicin infusions (10(-5) M) significantly stimulated both GLP-1, somatostatin, and VIP release to 111.1+/-4.5% (N = 9), 138.0+/-15.8% (N = 9) and 208.3+/-63.8% (N = 8) of basal release, respectively. Simultaneous addition of receptor antagonists to all three tachykinin receptors (CP96345, SR48968, and SR142801, all at 10(-6) M) significantly inhibited the effect of capsaicin on VIP release, whereas the release of GLP-1 and somatostatin was unaffected. We conclude that tachykinins potently stimulate the release of GLP-1, somatostatin, and VIP in the porcine ileum via NK-1 receptors. The effect on somatostatin and VIP is partly mediated via cholinergic neurons. Sensory neurons releasing tachykinins could be involved in the regulation of VIPergic neurons.
 ...
PMID:Tachykinins stimulate release of peptide hormones (glucagon-like peptide-1) and paracrine (somatostatin) and neurotransmitter (vasoactive intestinal polypeptide) from porcine ileum through NK-1 receptors. 1048 5

Recently we reported using minilibraries to replace Lys(9) [somatostatin (SRIF) numbering] of the potent somatostatin agonist L-363,301 (c[-Pro-Phe-D-Trp-Lys-Thr-Phe-]) to generate the potent neurokinin receptor (NK-1) antagonist c[-Pro-Phe-D-Trp-p-F-Phe-Thr-Phe-]. This novel cyclic hexapeptide did not bind the SRIF receptor. Thus, a single mutation converted L-363,301, a SRIF agonist with potency ca. 2-8 times the potency of SRIF in laboratory animals,(24) into a selective NK-1 receptor antagonist with an IC(50) of 2 nM in vitro. During the screening of the same libraries for ligands of the delta-opioid receptor, we identified four compounds (1-4) which represent a new class of delta-opioid antagonists, some of which were also NK-1 receptor antagonists. The most potent delta-opioid antagonist, c[-Pro-1-Nal-D-Trp-Tyr-Thr-Phe-] (2), showed a K(e) value of 128 nM in the mouse vas deferens assay and a delta-receptor binding affinity constant of 152 nM in the rat brain membrane binding assay. These results are of interest because they represent a novel class of delta-opioid antagonists and, like two previously reported delta-opioid antagonists, they lack a positive charge. To examine further the requirement for a positive charge in the delta-opioid ligands, we prepared two analogues of the beta-casomorphin-derived mixed mu-agonist/delta-antagonist, H-Dmt-c[-D-Orn-2-Nal-D-Pro-Gly-] (7), in which we eliminated the positive charge either through formylation of the primary amino group (5) or by the deletion of this N-terminal amino group (6). These latter compounds proved to be delta-opioid antagonists with K(e) values in the 16-120 nM range, as well as fairly potent mu-opioid antagonists (K(e) approximately 200 nM). These six compounds provide the most convincing evidence to date that there is no requirement for a positive charge in mu- and delta-opioid receptor antagonists. In addition, cyclic hexapeptide 4 lacks a phenolic hydroxyl group. Taken together, these data suggest that the prevailing assumptions about delta- and mu-opioid receptor binding need revision and that the receptors for these opioid ligands have much in common with the NK-1 and somatostatin receptors.
 ...
PMID:Novel ligands lacking a positive charge for the delta- and mu-opioid receptors. 1069 81

The localization, release, and effects of substance P and neurokinin A were studied in the porcine pancreas and the localization of substance P immunoreactive nerve fibers was examined by immunohistochemistry. The effects of electrical vagus stimulation and capsaicin infusion on tachykinin release and the effects of substance P and neurokinin A infusion on insulin, glucagon, somatostatin, and exocrine secretion were studied using the isolated perfused porcine pancreas with intact vagal innervation. NK-1 and NK-2 receptor antagonists were used to investigate receptor involvement. Substance P immunoreactive nerve fibers were localized to islets of Langerhans, acini, ducts, and blood vessels. Vagus stimulation had no effect on substance P and neurokinin A release, whereas capsaicin infusion stimulated release of both. Substance P and neurokinin A infusion increased release of insulin, glucagon, and exocrine secretion, whereas somatostatin secretion was unaffected. The effect of substance P on insulin, glucagon, and exocrine secretion was blocked by the NK-1 receptor antagonist. The effect of electrical stimulation of vagus nerves on insulin and exocrine secretion was not influenced by tachykinin receptor antagonists. We conclude that tachykinins stimulate both endocrine and exocrine pancreatic functions through NK-1 receptors. Tachykinins are not involved in vagal regulation of pancreatic secretion in pigs but could constitute part of an alternative stimulatory system.
 ...
PMID:Tachykinins in the porcine pancreas: potent exocrine and endocrine effects via NK-1 receptors. 1076 49


1 2 Next >>