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)

1. Neurogenic plasma extravasation evoked by topical application of 1% vv(-1) mustard oil on the skin of the acutely denervated rat hindleg (primary reaction) inhibited the development of a subsequent oil-induced plasma extravasation induced in the skin of the contralateral hindleg by 49.3+/-7.06% (n=9) and in the conjunctival mucosa due to 0.1% wv(-1) capsaicin instillation by 33.5+/-10.05% (n=6). The primary reaction also inhibited the non-neurogenic hindpaw oedema evoked by s.c. injection of 5% wv(-1) dextran into the chronically denervated hindpaw by 48.0+/-4.6% (n= 5). 2. Capsaicin injection (100 microg ml(-1) in 50 microl, s.c.) into the acutely denervated hindleg caused 56.5+/-4.0% (n=5) inhibition in the intensity of plasma extravasation elicited by 1% vv(-1) mustard oil smearing on the contralateral side. After chronic denervation, subplantar injection of 5% wv(-1) dextran elicited a non-neurogenic inflammatory response with intensive tissue oedema without causing any systemic anti-inflammatory effect. Bilateral adrenalectomy did not inhibit the mustard oil-induced anti-inflammatory effect in the contralateral hindleg. 3. Pretreating the rats with polyclonal somatostatin antiserum (0.5 ml rat(-1), i.v.) or with the somatostatin depleting agent cysteamine (280 mg kg(-1), s.c.) prevented the inhibitory action of mustard oil-induced inflammation on subsequent neurogenic plasma extravasation and strongly diminished the inhibition of non-neurogenic oedema formation evoked by dextran. 4. Exogenous somatostatin (10 microg kg(-1), i.p.) caused a 30.3+/-8.3% (n=6) inhibition of plasma extravasation caused by mustard oil smearing on the acutely denervated hindleg and this inhibitory effect was abolished by somatostatin antiserum (0.5 ml rat(-1), i.v.). The plasma level of somatostatin-like immunoreactivity (SST-LI) increased by 40.03+/-6.8% (n= 6) 10 min after topical application of 1% vv(-1) mustard oil on the acutely denervated hindpaws compared to the paraffin oil treated control group. Chronic denervation of the hindlegs or cysteamine (280 mg kg(-1), s.c.) pretreatment prevented the mustard oil-induced elevation of SST-LI in plasma. 5. It is concluded that chemical excitation of the capsaicin-sensitive sensory receptors not only induces local neurogenic plasma extravasation but also inhibits the development of a subsequent inflammatory reaction at remote sites of the body in the rat. A role for somatostatin in this systemic anti-inflammatory effect is suggested.
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PMID:Systemic anti-inflammatory effect induced by counter-irritation through a local release of somatostatin from nociceptors. 983 33

Capsaicin-sensitive neurones release a number of neuropeptides, such as substance P, neurokinin A, somatostatin and calcitonin gene-related peptide (CGRP), which exert a number of effects on smooth muscle tissues. Endothelin-1 was thought to potentiate the capsaicin-evoked release of neuropeptides from sensory neurones of the rat. We have investigated the neuromodulatory effects of endothelin-1 on capsaicin-induced release of neurotransmitters from rat vas deferens. Capsaicin and human alpha calcitonin gene-related peptide (human alphaCGRP) reduced the rat vas deferens twitch responses induced by electrical field stimulation. Human beta calcitonin gene-related peptide-(8-37) [human betaCGRP-(8-37)] (1 microM), a selective alphaCGRP receptor antagonist, antagonized the inhibitory effects of both drugs. Endothelin-1 concentration dependently evoked an increase in basal tone of the musculature and potentiated the amplitude of the electrically stimulated responses, blocking inhibitory effects of capsaicin but not of human alphaCGRP. Moreover, endothelin-1 did not markedly change the inhibitory effects of papaverine (0.1-100 microM) or isoprenaline (1 nM-100 microM) on responses to electrical field stimulation. FR 139317 [(N,N-hexamethylene) carbamoyl-Leu-D-Trp(N-Me)-D-2-Pya], a selective endothelin ET(A) receptor antagonist, administered 30 min before endothelin-1 restored the capsaicin effects whereas BQ 788 [Dmpc-gamma-MeLeu-D-Trp-(1-methoxycarbonyl)-D-Nle], a selective endothelin ET(B) receptor antagonist, was completely ineffective. The endothelin-1-induced block of the capsaicin effect was resistant to tetrodotoxin (1 microM) and 30-min pre-treatment with MEN 10.627 (cyclo[(Met-Asp-Trp-Phe-Dap-Leu) cyclo (2beta-5beta)]), a selective tachykinin NK2 receptor antagonist, did not abolish the endothelin-1 effect on the inhibitory response to capsaicin. These results suggest that endothelin-1 selectively inhibits the capsaicin-induced release of neurotransmitters from rat vas deferens and these effects are mediated via endothelin ET(A) receptors but not by tachykinin release.
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PMID:Endothelin-1 affects capsaicin-evoked release of neuropeptides from rat vas deferens. 993 22

CCK exhibits a potent cytoprotective activity against acute gastric lesions, but its role in ulcer healing has been little examined. In this study we determined whether exogenous CCK or endogenously released CCK by camostate, an inhibitor of luminal proteases, or by the diversion of pancreatico-biliary secretion from the duodenum, could affect ulcer healing. In addition, the effects of antagonism of CCK-A receptors (by loxiglumide, LOX) or CCK-B receptors (by L-365,260), an inhibition of NO-synthase by N(G)-nitro-L-arginine (L-NNA), or sensory denervation by large neurotoxic dose of capsaicin on CCK-induced ulcer healing were examined. Gastric ulcers were produced by serosal application of acetic acid and animals were sacrificed 9 days after ulcer induction. The area of ulcers and blood flow at the ulcer area were determined. Plasma levels of gastrin and CCK and luminal somatostatin were measured by RIA and mucosal biopsy samples were taken for histological evaluation and measurement of DNA synthesis. CCK given s.c. reduced dose dependently the ulcer area; the threshold dose of CCK being 1 nmol/kg and the dose inhibiting this area by 50% being 5 nmol/kg. This healing effect of CCK was accompanied by a significant increase in the GBF at ulcer margin and the rise in luminal NO production, plasma gastrin level and DNA synthesis. Concurrent treatment with LOX, completely abolished the CCK-8-induced acceleration of the ulcer healing and the rise in the GBF at the ulcer margin, whereas L-365,260 remained without any influence. Treatment with camostate or diversion of pancreatic juice that raised plasma CCK level to that observed with administration of CCK-8, also accelerated ulcer healing and this effect was also attenuated by LOX but not by L-365,260. Inhibition of NO-synthase by L-NNA significantly delayed ulcer healing and reversed the CCK-8 induced acceleration of ulcer healing, hyperemia at the ulcer margin and luminal NO release, and these effects were restored by the addition to L-NNA of L-arginine but not D-arginine. Capsaicin denervation attenuated CCK-induced ulcer healing, and the accompanying rise in the GBF at the ulcer margin and decreased plasma gastrin and luminal release of somatostatin when compared to those in rats with intact sensory nerves. Detectable signals for CCK-A and B receptor mRNAs as well as for cNOS mRNA expression were recorded by RT-PCR in the vehicle control gastric mucosa. The expression of CCK-A receptor mRNA and cNOS mRNA was significantly increased in rats treated with CCK-8 and camostate, whereas CCK-B receptor mRNA remained unaffected. We conclude that CCK accelerates ulcer healing by the mechanism involving upregulation of specific CCK-A receptors, enhancement of somatostatin release, stimulation of sensory nerves and hyperemia in the ulcer area, possibly mediated by NO.
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PMID:Acceleration of ulcer healing by cholecystokinin (CCK): role of CCK-A receptors, somatostatin, nitric oxide and sensory nerves. 1045 43

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.
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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

In the rat stomach, evidence has been provided that capsaicin-sensitive sensory nerves (CSSN) are involved in a local defense mechanism against gastric ulcer. In the present study capsaicin or resiniferatoxin (RTX), a more potent capsaicin analogue, was used to elucidate the role of these sensory nerves in gastric mucosal protection, mucosal permeability, gastric acid secretion and gastrointestinal blood flow in the rat. In the rat stomach and jejunum, intravenous RTX or topical capsaicin or RTX effected a pronounced and long-lasting enhancement of the microcirculation at these sites, measured by laser Doppler flowmetry technique. Introduction of capsaicin into the rat stomach in very low concentrations of ng-microg x mL(-1) range protected the gastric mucosa against damage produced by topical acidified aspirin, indomethacin, ethanol or 0.6 N HCl. Resiniferatoxin exhibited acute gastroprotective effect similar to that of capsaicin and exerted marked protective action on the exogenous HCl, or the secretagogue-induced enhancement of the indomethacin injury. The ulcer preventive effect of both agents was not prevented by atropine or cimetidine treatment. Capsaicin given into the stomach in higher desensitizing concentrations of 6.5 mM markedly enhanced the susceptibility of the gastric mucosa and invariably aggravated gastric mucosal damage evoked by later noxious challenge. Such high desensitizing concentrations of capsaicin, however, did not reduce the cytoprotective effect of prostacyclin (PGI2) or beta-carotene. Capsaicin or RTX had an additive protective effect to that of atropine or cimetidine. In rats pretreated with cysteamine to deplete tissue somatostatin, capsaicin protected against the indomethacin-induced mucosal injury. Gastric acid secretion of the pylorus-ligated rats was inhibited with capsaicin or RTX given in low non-desensitizing concentrations, with the inhibition being most marked in the first hour following pylorus-ligation. Low intragastric concentrations of RTX reduced gastric hydrogen ion back-diffusion evoked by topical acidified salicylates. It is concluded that the gastropotective effect of capsaicin-type agents involves primarily an enhancement of the microcirculation effected through local release of mediator peptides from the sensory nerve terminals. A reduction in gastric acidity may contribute to some degree in the gastric protective action of capsaicin-type agents. The vasodilator and gastroprotective effects of capsaicin-type agents do not depend on vagal efferents or sympathetic neurons, involve prostanoids, histaminergic or cholinergic pathways.
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PMID:Capsaicin-sensitive afferent sensory nerves in modulating gastric mucosal defense against noxious agents. 1067 23

We examined the role of capsaicin-sensitive afferent neurons in pH-dependent gastrin secretion in the rat stomach. The change in serum gastrin levels relative to changes in luminal pH (using omeprazole for luminal alkalization or 0.1 N HCl for luminal acidification) was studied after oral administration of 4% lidocaine or capsaicin-induced ablation of afferent neurons. The increase of serum gastrin levels by luminal alkalization was significantly inhibited (50%) after administration of 4% lidocaine. Capsaicin pretreatment (125 mg/kg subcutaneously over two days) inhibited the change in serum gastrin levels both the luminal alkalization (38%) and acidification (66%). Antral gastrin contents, somatostatin contents, gastrin mRNA expression, and somatostatin mRNA expression were not significantly affected by capsaicin pretreatment. Our results indicate that capsaicin-sensitive afferent neurons participate in the secretion of gastrin by luminal alkalization and inhibition of gastrin by luminal acidification.
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PMID:Acid-sensitive and alkaline-sensitive sensory neurons regulate pH dependent gastrin secretion in rat. 1087 40

Capsaicin, the pungent ingredient of chilli peppers has become a "hot" topic in neuroscience with yearly publications over half thousand papers. It is outlined in this survey how this exciting Hungarian research field emerged from almost complete ignorance. From the initial observation of the phenomenon of "capsaicin desensitization", a long-lasting chemoanalgesia and impairment in thermoregulation against heat, the chain of new discoveries which led to the formulation of the existence of a "capsaicin receptor" on C-polymodal nociceptors is briefly summarized. Neurogenic inflammation is mediated by these C-afferents which are supplied by the putative capsaicin receptor and were termed as "capsaicin sensitive" chemoceptive afferents. They opened new avenues in local peptidergic regulation in peripheral tissues. It has been suggested that in contrast to the classical axon reflex theory, the capsaicin-sensitive sensory system subserves a "dual sensory-efferent" function whereby initiation of afferent signals and neuropeptide release are coupled at the same nerve endings. Furthermore, in the skin at threshold stimuli which do not evoke sensation elicit already maximum efferent response as enhanced microcirculation. In isolated organ preparations large scale of new type of peptidergic capsaicin-sensitive neurogenic smooth muscle responses were revealed after the first one was described by ourselves on the guinea-pig ileum in 1978. Recently the "capsaicin receptor" has been cloned and it is now named as the "transient receptor potential vanilloid 1" (TRPV1). Hence, capsaicin research led to the discovery of the first temperature-gated ion channel gated by noxious heat, protons, vanilloids and endogenous ligands as anandamide, N-oleoyldopamine and lipoxygenase products. Another recent achievement is the discovery of a novel "unorthodox" neurohumoral regulatory mechanism mediated by somatostatin. Somatostatin released from the TRPV1-expressing nerve endings reaches the circulation and elicits systemic antiinflammatory and analgesic "sensocrine" functions with counter-regulatory influence e.g. in Freund's adjuvant-induced chronic arthritis. Nociceptors supplied by TRPV1 and sst4 somatostatin receptors has become nowadays promising targets for drug development.
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PMID:Forty years in capsaicin research for sensory pharmacology and physiology. 1556 73

Ecabet sodium (ecabet), a cytoprotective drug, produces an increase in mucosal blood flow. One of the gastrointestinal motility regulatory factors has been assumed to be the induction of changes in the levels of peptides (gastrin, somatostatin and motilin) in plasma. On the other hand, recently, capsaicinsensitive afferent nerves were shown to play an important role in gastric mucosal defensive mechanism. Capsaicin stimulates afferent nerves and enhances the release of calcitonin gene-related peptide (CGRP) and substance P in the stomach. We studied the effect of ecabet on human plasma gastrin-, somatostatin-, motilin-, CGRP- and substance P-like immunoreactive substance (IS) in healthy subjects. Ecabet sodium at a dose of 3.0 g, or placebo, was orally administered in five healthy males. The blood samples were taken before and at 20, 40, 60, 90, 120, 180 and 240 min after administration, subjected to extracting procedures, and submitted to a highly sensitive enzyme immunoassay system. Single administration of ecabet caused significant (P<0.05) increases in plasma CGRP-, substance P- and somatostatin-IS concentration compared with placebo. Ecabet significantly decreased plasma gastrin-IS levels compared with placebo. In this study, we hypothesized that ecabet might stimulate capsaicin-sensitive afferent nerves indirectly and improve mucosal blood flow; this might be a key mechanism underlying its gastroprotective action.
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PMID:Ecabet sodium raises plasma levels of calcitonin generelated peptide and substance P in healthy humans. 1596 37

Capsaicin-sensitive, TRPV1 (transient receptor potential vanilloid 1) receptor-expressing primary sensory neurons exert local and systemic efferent effects besides the classical afferent function. The TRPV1 receptor is considered a molecular integrator of various physico-chemical noxious stimuli. In the present study its role was analysed in acute nociceptive tests and chronic neuropathy models by comparison of wild-type (WT) and TRPV1 knockout (KO) mice. The formalin-induced acute nocifensive behaviour, carrageenan-evoked inflammatory mechanical hyperalgesia and partial sciatic nerve lesion-induced neuropathic mechanical hyperalgesia were not different in WT and KO animals. Acute nocifensive behaviour after intraplantar injection of phorbol 12-myristate 13-acetate, an activator of protein kinase C (PKC), was absent in TRPV1 KO animals showing that PKC activation elicits nociception exclusively through TRPV1 receptor sensitization/activation. Thermal hyperalgesia (drop of noxious heat threshold) and mechanical hyperalgesia induced by a mild heat injury (51 degrees C, 15s) was smaller in KO mice suggesting a pronociceptive role for TRPV1 receptor in burn injury. Chronic mechanical hyperalgesia evoked by streptozotocin-induced diabetic and cisplatin-evoked toxic polyneuropathy occurred earlier and were greater in the TRPV1 KO group. In both polyneuropathy models, at time points when maximal difference in mechanical hyperalgesia between the two groups was measured, plasma somatostatin concentrations determined by radioimmunoassay significantly increased in WT but not in TRPV1 KO mice. It is concluded that sensitization/activation of the TRPV1 receptor plays a pronociceptive role in certain models of acute tissue injury but under chronic polyneuropathic conditions it can initiate antinociceptive counter-regulatory mechanisms possibly mediated by somatostatin released from sensory neurons.
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PMID:Investigation of the role of TRPV1 receptors in acute and chronic nociceptive processes using gene-deficient mice. 1615 May 43

Substance P (SP) and calcitonin gene-related peptide (CGRP), released from capsaicin-sensitive sensory nerves induce local neurogenic inflammation, while somatostatin exerts systemic anti-inflammatory actions. The aim of the present study was to investigate the release of pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) and its effects on sensory neuropeptide release in vitro and acute neurogenic ear swelling in vivo. Capsaicin (10(-6) M) or electrical field stimulation (EFS; 40 V, 0.1 ms, 10 Hz, 120 s; 1200 impulses)-induced release of PACAP-38, SP, CGRP and somatostatin from isolated rat tracheae was measured with radioimmunoassay. Mustard oil-induced neurogenic inflammation in the mouse ear was determined with a micrometer and in the rat hind paw skin by the Evans Blue leakage technique. Capsaicin and EFS evoked 27% and more than twofold elevation of PACAP-38 release respectively, compared with the prestimulated basal values from isolated trachea preparation. Exogenously administered PACAP-38 (20-2000 nM) diminished both capsaicin- and EFS-evoked sensory neuropeptide release in a concentration-dependent manner. The maximal inhibitory effects of PACAP on capsaicin-induced substance P, CGRP and somatostatin release amounted to 75.4%, 73.3% and 90.0%, while EFS-evoked release of these peptides was 80.03%, 87.7% and 67.7%. In case of capsaicin stimulation the EC50 values for substance P, CGRP and somatostatin were 82.9 nM, 60.1 nM and 66.9 nM, respectively. When EFS was performed, these corresponding EC50 data were 92.1 nM, 67.8 nM and 20.9 nM. PACAP-38 (10, 100 and 1000 microg/kg i.p. in 200 microl volume) inhibited neurogenic ear swelling in the mouse. Furthermore, 100 microg/kg i.p. PACAP also significantly diminished mustard oil-evoked plasma protein extravasation in the rat skin. These results suggest that PACAP-38 is released from the stimulated peripheral terminals of capsaicin-sensitive afferents and it is able to inhibit the outflow of sensory neuropeptides. Based on this mechanism of action PACAP is also able to effectively diminish/abolish neurogenic inflammatory response in vivo after systemic administration.
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PMID:Effect of pituitary adenylate cyclase activating polypeptide-38 on sensory neuropeptide release and neurogenic inflammation in rats and mice. 1693 9


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