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 potency of several peptides and drugs as histamine liberators was assessed using the rat isolated hind limb preparation. Neurotensin (NT) and compound 48/80 (C48/80) were effective in concentrations as low as 10(-9) M and 10(-8) M, respectively. Threshold concentrations of vasoactive intestinal peptide (VIP) and substance P (SP) varied between 5 X 10(-7) to 5 X 10(-6) M while somatostatin (SS) was barely active at 6 X 10(-6) M. No histamine release could be detected following the use of high concentrations of thyrotropin releasing hormone (TRH) (6 X 10(-6) M), dynorphin (DYN) (6 X 10(-6) M) bradykinin (BK), des-Arg9-BK or bombesin (BB) (at 10(-5) M). Poly-L-Lysine and the calcium ionophore A23187 were about 100 times less active than NT. Concanavalin A (Con A) was inactive at 10(-6) M. These results indicate that NT is more potent (on a molar basis) as histamine liberator in the rat hind limb preparation (which contains a large population of cutaneous and subcutaneous mast cells) than any of the other compounds tested. Histamine release by NT was inhibited by preexposure of the rat hind limb mast cells to a high concentration of SP (1.5 X 10(-6) M). This result adds further support to the hypothesis suggesting that NT and SP might share a common mechanism of action and/or act through common receptors at least in rat mast cells.
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PMID:Potency of various peptides as histamine liberators in the rat hind limb. 241 86

A bland procedure, conducted in ice, is described for the extraction with HCl of smooth-muscle-contracting substances from plexus-containing ileal longitudinal muscle (l.m.) sheets obtained mainly from rabbits and some guinea-pigs. The spasmogenic activity in rabbit extracts was distinguished from acetylcholine, histamine and 5-hydroxytryptamine by antagonists; and from prostaglandins, by its insolubility in ether at acid pH and by pretreatment of the animals with indomethacin. The fact that it contracts the separated l.m. of the guinea-pig ileum, whether plexus-containing or plexus-free, and in atropine distinguishes it also from methionine-enkephalin, somatostatin, 13-norleucine motilin, bombesin, and cholecystokinin octapeptide (CCK8). This activity was partially purified, first by several partitions with ether at pH 1.4-2.2 and then by treatment at pH 4.5-5 with lead acetate. The virtual absence of ATP was confirmed by the firefly bioluminescence technique. The guinea-pig-ileum-contracting component in the partially purified extracts was destroyed by pepsin, chymotrypsin and DPCC-treated trypsin, indicating its peptide nature and distinguishing it from oxytocin, vasopressin, bradykinin, etc. In parallel assays the partially purified rabbit extracts were considerably more active than Substance P on jird or rat ascending colons than on the guinea-pig l.m., suggesting the presence of a second spasmogenic component in the extracts. In guinea-pig extracts the partially purified activity was 8-16 times greater when plexus-containing than when plexus-free, pointing to Auerbach's plexus as the source of the activity.
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PMID:Extraction and partial purification of spasmogenic substances in Auerbach's plexus. 242 21

1. We examined the possibility that the neuropeptide, galanin, may act as a transmitter in longitudinal muscle isolated from the rat ileum. 2. Galanin at nanomolar concentrations produced a phasic contraction with a concomitant increase in rhythmic activity. At concentrations in excess of 3 x 10(-8) M, the contraction was followed by a rapid desensitization; hence, with the cumulative re-addition of galanin, there was no response. This desensitization was probably selective for galanin because there was no attenuation of the contractile responses to substance P, neurokinin A and B, bradykinin or carbachol. 3. The phasic contraction induced by galanin was not inhibited by atropine, guanethidine, hexamethonium, naloxone, tetrodotoxin or [D-Pro2, D-Trp7,9]-substance P. 4. Electrical stimulation of intramural nerves at low frequencies (1-5 Hz) led to an augmentation of spontaneous rhythmic contractions, which were completely or partially inhibited by atropine. However, guanethidine, hexamethonium, naloxone, [D-Pro2, D-Trp7,9]-substance P and desensitization to galanin were without effect on the response to such electrical stimulation. 5. In contrast, transmural electrical stimulation at higher frequencies in the presence of atropine and guanethidine produced biphasic contractile responses with transient and slow components. The slow component was selectively attenuated by galanin desensitization. 6. The slow component induced by high frequency stimulation was markedly attenuated by repeated electrical stimulation at short intervals (2.5 min between 30 s trains). Following repeated stimulation, the contractile response to galanin was also attenuated. Thus, a cross-desensitization between the mediator of the slow component and galanin had to be considered. In contrast, responses to tachykinins and the transient component induced by electrical stimulation were without effect. 7. Somatostatin, vasoactive intestinal polypeptide and alpha,beta-methylene ATP were without effect on the tone of the muscle. Calcitonin gene-related peptide, neurotensin, gastrin-releasing peptide, neuropeptide Y and capsaicin produced either a transient arrest of the spontaneous rhythmic activity or a transient relaxation. 8. These results suggest that the slow component of the non-cholinergic non-adrenergic contraction, as induced by intramural nerve stimulation is apparently due to the endogenous release of galanin, presumably released from galanin-containing nerves in the rat ileum.
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PMID:Contribution of galanin to non-cholinergic, non-adrenergic transmission in rat ileum. 246 26

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.
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PMID:Characterization of neuropeptide-induced histamine release from human dispersed skin mast cells. 246 82

To study the nature and extent of mast cell heterogeneity within a single species, we have developed methodologies to isolate rat lung mast cells (LMC) and have compared these to peritoneal mast cells (PMC) and intestinal mucosal mast cells (IMMC). In normal and athymic nude (rnu/rnu) rats, a single intratracheal administration of bleomycin (5 U/kg) leads to pulmonary fibrosis accompanied by parenchymal hyperplasia of mast cells that are histochemically like PMC rather than IMMC. Using collagenase digestion of fibrotic rat lungs (30-80 days after bleomycin treatment), we recovered an average of 58.1 x 10(6) viable cells per rat, containing 2.5% mast cells. Control experiments in which PMC were subjected to the isolation procedure used for LMC showed that there was no qualitative effect on PMC, but that a reduction of 26-60% in responsiveness to secretagogues occurred. Isolated LMC secreted histamine in response to 48/80, A23187, substance P, VIP and somatostatin and bradykinin, but at lower levels than PMC. The anti-allergic compound theophylline, which does not inhibit antigen-induced histamine secretion by IMMC, was effective against both LMC and PMC. Taken together, the thymus independence of pulmonary mast cell hyperplasia, the histochemical characteristics and the responsiveness to secretagogues and anti-allergic compounds indicate that the majority of dispersed LMC are similar to PMC rather than to IMMC. Whether LMC should be considered analogous to PMC or, because of their size, histamine content and responsiveness to many secretagogues, intermediate between PMC and IMMC, remains to be determined through additional studies.
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PMID:Isolation and characterization of lung mast cells from rats with bleomycin-induced pulmonary fibrosis. 246 79

Neurotensin, bradykinin and somatostatin inhibited in a time- and concentration-dependent manner prostaglandin E1- or forskolin-stimulated cAMP production in neuroblastoma N1E115 cells. Cell treatment with 1 microgram/ml pertussis toxin for 6 hours reversed the inhibition elicited by peptides after short incubation periods (less than or equal to 1 min) but, in contrast, had no effect after longer incubation periods (greater than or equal to 3 min). Fluoroaluminate also inhibited prostaglandin E1-stimulated cAMP production in N1E115 cells, and this effect was not reversed by pertussis toxin. The 6 hour treatment with pertussis toxin was shown to be sufficient to ADP ribosylate virtually all of the 41 kD protein substrate corresponding to the alpha subunit of Gi. Protein kinase C activation with phorbol ester did not inhibit basal or stimulated cAMP production. Our data point to the existence of both pertussis toxin sensitive and insensitive mechanisms of neuropeptide-mediated inhibition of cAMP formation in N1E115 cells. The toxin insensitive response is not mediated by protein kinase C. The possibility is discussed that it results from the activation of a pertussis toxin insensitive G protein.
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PMID:Neurotensin, bradykinin and somatostatin inhibit cAMP production in neuroblastoma N1E115 cells via both pertussis toxin sensitive and insensitive mechanisms. 256 13

The effect of a low-dose bradykinin (BK) infusion (30 ng/kg min) on glucagon-induced hepatic glucose production and glucose cycling was studied in five normal volunteers. Studies were performed during constant insulin concentration as achieved by simultaneous somatostatin infusion and insulin replacement. In the basal period glucagon was infused at a rate of 0.5 ng/kg min. Then, glucagon infusion rate was increased to 3 ng/kg min to test the response to hyperglucagonemia. In a second set of experiments BK was infused concomitantly with the high dose glucagon. Each subject served as his own control. BK infusion did not prevent the glucagon-induced rise in hepatic glucose production and glucose cycling. However, at a later stage BK accelerated the negative feedback mechanisms activated by glucagon (decrease in hepatic glucose production) significantly. These findings suggest that intravenous BK may interact with mechanisms involved in the down-regulation of hepatic glucagon effects.
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PMID:Glucagon and hepatic glucose production: modulation by low-dose bradykinin infusion. 257 Mar 43

1. The intracellularly-recorded electrical and mechanical responses to field stimulation of intramural nerves in three sympathetically-innervated smooth muscles--the mouse vas deferens, the rabbit ear artery and the rabbit mesenteric bed preparation were investigated. 2. In each tissue there was evidence for co-transmission involving noradrenaline (NA) and adenosine 5'-triphosphate (ATP) or a closely related nucleotide. 3. The electrical response in each tissue consisted of excitatory junction potentials (ejps) which were abolished by alpha, beta-methylene ATP (alpha, beta MeATP, 1-10 X 10(-6) M), suggesting that they were mediated by ATP. Only in the rabbit ear artery was there an additional electrical event mediated by NA. This took the form of a small slow membrane depolarization which followed the ejps and which was antagonized by either of the alpha-adrenoreceptor blocking agents phentolamine (1 X 10(-6) M) or prazosin (1 X 10(-7) M). 4. In the mouse vas deferens and rabbit mesenteric artery, both transmitter substances (NA and ATP) played a role in the contractile response to field stimulation. In the rabbit ear artery, NA alone appeared to mediate the contractile event. 5. Contractile responses to nerve-released ATP were accompanied by a membrane potential change, whereas those to NA appeared to be mediated largely by a voltage-independent mechanism. 6. In the mouse vas deferens, the ejps and action potentials evoked by field stimulation appeared to be mediated by a discrete increase in permeability to Na+ and K+. 7. In the mouse vas deferens, local application of bradykinin (1-100 X 10(-7) M) produced a small, slow membrane hyperpolarization. VIP (1-100 X 10(-7) M), neuropeptide Y (1-100 X 10(-7) M), substance P (1-100 X 10(-7) M), somatostatin (1-100 X 10(-7) M), leu-enkephalin (1-100 X 10(-7) M), metenkephalin (1-100 X 10(-7) M) and bombesin (1-100 X 10(-7) M), similarly applied, each produced no significant change in membrane potential. None of these peptides appear to be the transmitter mediating the ejp in this tissue.
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PMID:The electrical and mechanical basis of co-transmission in some vascular and non-vascular smooth muscles. 284 46

Somatostatin (SRIF) is a putative peptide neurotransmitter that may interact with brain capillaries following neurosecretion of the peptide. The present studies investigate the binding and metabolism of SRIF analogues in isolated bovine brain microvessels. 125I-[Tyr1]SRIF was rapidly degraded by capillary aminopeptidase with a half-time of approximately 3 min at 23 degrees C. The microvessel aminopeptidase had a low affinity and high capacity for the peptide, Km = 76 microM and Vmax = 74 nmol min-1 mgp-1. 125I-[Tyr11]SRIF was converted to free iodotyrosine at a much slower rate, presumably by a lower-activity endopeptidase. 125I-[Try11]SRIF was rapidly bound by microvessels, whereas another basic peptide, [Tyr8]bradykinin, or an acidic peptide, CCK8, or a neutral peptide, leucine enkephalin, were bound to a considerably less extent. The binding of 125I-[Tyr11]SRIF to the capillaries was nonsaturable up to a concentration of 1 microgram/ml of unlabeled peptide, and the binding reaction was extremely rapid, reaching equilibrium within 5 s at either 0 degrees C or 37 degrees C. Approximately 20% of the SRIF bound by the microvessels was resistant to acid wash and presumably represented internalized peptide. In addition, the 125I-[Tyr11]SRIF bound rapidly to the endothelial cytoskeleton remaining after a 1% Triton X-100 extraction of the microvessels. The peptide-cytoskeletal binding reaction was nonsaturable up to 1 microgram/ml of unlabeled [Tyr11]SRIF, but it was inhibited by 0.5% polylysine or 0.8 M KCl and was stimulated by 1 mM dithiothreiotol. These studies suggest that brain microvessels rapidly sequester and degrade SRIF analogues and that this may represent one mechanism for rapid inactivation of the neuropeptides subsequent to neurosecretion.
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PMID:Rapid sequestration and degradation of somatostatin analogues by isolated brain microvessels. 285 72

We reported recently the presence of somatostatin-like immunoreactivity (SLI) in the glomerulus of rat kidney. In the present study, we examined factors affecting SLI release from isolated rat glomeruli using a perifusion system. Perifusate containing a mixture of essential amino acids stimulated SLI release, while other hormonal agents such as parathyroid hormone, vasopressin, angiotensin II, bradykinin, epinephrine, PGE2, known to have direct actions on the glomerulus, had no discernible effect on SLI release. Addition of somatostatin to the perifusate did not affect either basal or angiotensin II-stimulated PGE2 release from isolated glomeruli. Our preliminary results demonstrate the stimulatory effect of mixed amino acids on somatostatin release from isolated glomeruli. Further studies are needed to elucidate the possible physiological significance of the present findings.
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PMID:Amino acids release somatostatin-like immunoreactivity from isolated rat glomeruli. 286 84


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