Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The localization of Substance P(SP)-, Methionine-Enkephalin(met-Enk)-, Somatostatin(SOM)- Serotonin(SER)-, Cholecystokinin(CCK)-, and Vasoactive intestinal polypeptide (VIP)-like immunoreactivity (-LIR) has been determined immunocytochemically in the thoracic spinal cord intermediate zone of male and female guinea pigs. All neuroactive substances studied are exclusively localized in nerve fibre varicosities and terminals building up the vegetative network of the thoracic spinal cord intermediate zone. This network is situated dorsally to the central canal as a longitudinal plate of approximate thickness of 90-100 microns. Immunoreactive fibres are observed in the two Fasciculi longitudinales laterales and the two Fasciculi longitudinales mediales which are interconnected by transverse and oblique peptide-containing bundles (the terminology used by Petras and Cummings 1972; Galabov and Davidoff 1976). All these bundles interconnect the nuclei intermediolaterales principales and funiculares, the nuclei intercalates spinales and the nuclei intercalates paraependimales in ipsi- and contralateral as well as in rostral and caudal direction. The neurones of these nuclei are surrounded by immunoreactive varicosities and terminals. The quantity of the immunoreactive structures and intensity of the staining varied for the different neuroactive substances. As to the origin of the vegetative network immunoreactive fibres three main possibilities exists: a). From primary afferent neurones situated in the dorsal root ganglia, which send their axons via the dorsal roots (mainly for SP and perhaps for CCK); b). From supraspinal neurones which send their axons descending in the white matter funiculi and in the fasciculi longitudinales laterales and mediales and c). From intrinsic spinal cord neurones, which send their neurites in ascending and descending directions, ipsi- and contralaterally and interconnect the spinal cord segments. The different origin of the vegetative network immunoreactive fibres as well as the complex innervation of the preganglionic sympathetic nerve cells in the intermediate zone of the spinal cord suggests that this network may play an important role in the integration of the central and peripheral vegetative nervous system as well as probably in the integration of the somatic and the vegetative nervous system.
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PMID:Localization of some neuropeptide- and serotonin-like immunoreactivities in the vegetative network of guinea pig spinal cord. 241 Apr 87

The enterochromaffin (EC) cell system is distributed throughout the entire gastrointestinal tract. Enterochromaffin cells are the major source of intestinal serotonin (5-HT), but separate subpopulations of EC cells may synthesize and store peptides as substance P (SP), motilin, and enkephalin as well. Of special interest is that 5-HT and SP, which may coexist in EC cells, have several functional similarities, i.e., inhibition of gastric acid secretion, stimulation of intestinal motility, and secretion of water and electrolytes. Carcinoid tumors are derived from the gut endocrine system. Depending on site of origin, carcinoids are divided into foregut, midgut, and hindgut derivatives with different clinical symptoms. A common biochemical feature of midgut carcinoids is the production of 5-HT and SP. Histochemically, midgut carcinoids are characterized by the argentaffin reaction--a direct reduction of silver salts owing to 5-HT. Specific antisera for the immunocytochemical demonstration of secretory products are available as well. Despite their relative infrequency, carcinoids are the most common small intestinal tumors. The common appendix tumors generally have a benign clinical course, whereas the small intestinal tumors have different growth patterns and frequently metastasize with increasing size, and may thus give rise to the carcinoid syndrome (diarrhea, facial flush, right-sided cardiac valvular disease, and asthma). Carcinoid symptoms first appear when hepatic inactivation of 5-HT is exceeded, unless the carcinoid has an extraintestinal localization, for example, ovarian lesions may elicit symptoms in the absence of hepatic disease owing to direct secretion into systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin and carcinoid tumors. 241 66

Serotonin (5-HT) and substance P (SP) were assayed in peripheral blood in patients with known midgut carcinoids and hepatic metastases. All patients had supranormal basal levels of 5-HT and SP. The clinical and hormonal response was evaluated by two provocation tests, pentagastrin (PG) injection or calcium infusion. Pentagastrin caused flushing and gastrointestinal symptoms and elevated levels of circulating 5-HT, but not of SP. Pretreatment with a 5-HT2 receptor blocking agent (ketanserin) alleviated gastrointestinal symptoms but had no influence on either 5-HT release or PG-induced flushing. Calcium infusion induced carcinoid symptoms in only two of six patients, which were associated with elevated 5-HT levels (whereas elevated SP levels were seen in only one patient). We conclude that 5-HT is important for the development of gastrointestinal symptoms but not of flushing. Ketanserin may alleviate gastrointestinal symptoms but does not influence PG-induced release of 5-HT. Substance P and 5-HT do not seem to share a common release mechanism. It appears that PG testing is superior to calcium infusion as a provocative test in patients with the carcinoid syndrome.
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PMID:The pentagastrin test in the diagnosis of the carcinoid syndrome. 241 67

Neurons surrounding the central canal in sacral spinal segments were functionally characterized on the basis of somatic and/or visceral afferent input, then intracellularly marked with horseradish peroxidase (HRP). Tissue sections containing portions of HRP-stained neurons were subsequently immunohistochemically examined for the presence of contacts made by axonal enlargements containing vasoactive intestinal polypeptide (VIP), substance P (SP), somatostatin (SS), Leu-enkephalin (ENK), or serotonin (5-HT). ENK-and 5-HT-containing enlargements were found to contact all neurons examined. SP and SS terminals contacted fewer neurons, and were not associated with specific functional classes. On the other hand, VIP-containing fibers contacted only those neurons receiving visceral afferent input, thus supporting the contention that VIP is contained in a population of visceral afferent fibers projecting to the gray matter surrounding the central canal at sacral levels.
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PMID:Immunohistochemistry of synaptic input and functional characterizations of neurons near the spinal central canal. 241 42

Nervous tissue was analyzed for possible mediators of neurogenic inflammation. Acid extracts of spinal cord or spinal roots contained activity causing plasma protein extravasation when injected into the rat abdominal skin. The activity was more than 1000-fold higher than could be attributed to the content of substance P (SP). It was not depleted from spinal cord after destruction of afferent C fibers by capsaicin and was resistant to proteolytic enzymes. The activity was clearly separated from SP or neurokinins by HPLC or gel filtration and was due to compounds of high polarity and low molecular weight. Further HPLC separated at least 6 peaks, two of which were found to contain adenosine and AMP, respectively, as active substances. The activity of these compounds and of the peaks was reduced by antihistaminics. A further compound identified was 5-HT. Thus, while several active non-peptidergic compounds were found, no clear evidence for a new mediator of neurogenic inflammation was obtained.
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PMID:The spinal cord contains multiple factors causing plasma protein extravasation in the skin. 241 48

The effects of the putative neurotransmitters acetylcholine, adrenaline, adenosine, ATP, bombesin, 5-hydroxytryptamine, met-enkephalin, neurotensin, somatostatin, substance P and VIP have been investigated in the perfused intestine of the cod, Gadus morhua. The presence and distribution of the different types of nerves was investigated with immunohistochemistry and Falck-Hillarp fluorescence histochemistry. A spontaneous rhythmic activity of the perfused preparations usually occurred within a few minutes from the start of the experiment. This activity was diminished or abolished by addition of atropine, methysergide or tetrodotoxin to the perfusion fluid. Acetylcholine, 5-hydroxytryptamine or substance P caused a contraction of the intestinal wall. The response to acetylcholine was blocked by atropine but not by tetrodotoxin, while the response to 5-hydroxytryptamine was blocked by methysergide and usually also by tetrodotoxin. This indicates that the effect of acetylcholine is direct on the muscle cells, while the effect of 5-hydroxytryptamine may be at least partly via a second neuron. All adrenergic agonists (adrenaline, isoprenaline and phenylephrine) had a dominating inhibitory effect on the intestine. Experiments with antagonists showed that the inhibition is due to stimulation of both alpha-adrenoceptors and beta-adrenoceptors. ATP, adenosine and somatostatin also caused a relaxation of the intestinal wall, often followed by a contraction. Met-enkephalin produced variable responses, either a relaxation, a contraction or both. Bombesin caused a weak inhibition, if anything. Neurotensin and VIP did not visibly affect the intestinal motility. 5-HT-, substance P- and VIP-like immunoreactivity and catecholamine fluorescence were observed in the myenteric plexus, submucosa and muscle layers in all parts of the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neurotransmitters in the intestine of the Atlantic cod, Gadus morhua. 241 59

The cardiovascular and respiratory effects of Substance P (SP) and Thyrotrophin-Releasing Hormone (TRH) microinjections into the nucleus tractus solitarius (NTS) of urethane anaesthetized rats have been investigated. Dual injections of the peptides with serotonin (5-HT) were given to investigate possible functional interactions. In addition, SP and TRH were injected into rats in which 5-HT in the NTS area had been depleted by prior treatment with 5,7-Dihydroxytryptamine (5,7-DHT). SP (65pmol) did not elicit significant effects on blood pressure (BP) or heart rate (HR), but produced a marked, acute reduction in respiration rate (RR). TRH (110pmol) elicited a small but significant reduction in mean arterial pressure (MAP), whereas 5-HT (15nmol) caused a rise in MAP. Neither TRH nor 5-HT modified RR when given alone. A dual injection of SP (6.5pmol, ineffective alone) and 5-HT (15nmol) resulted in a rise in MAP which was insignificantly different from the effect of 5-HT alone. However, a prolonged fall in RR, unlike the effect of SP alone was also observed. A dual injection of TRH (11pmol, ineffective alone) and 5-HT (15nmol) resulted in a profound fall of RR but no significant changes in MAP or HR. SP elicited similar effects in 5,7-DHT lesioned animals as in sham operated controls. In contrast, TRH microinjections in lesioned rats were associated with a profound fall in RR, and a blood pressure response significantly different to that observed in the corresponding sham group. The results are discussed in relation to other evidence suggesting functional interactions between neuropeptides and amine neurotransmitters in the mammalian brainstem.
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PMID:Cardio-respiratory actions of substance P, TRH and 5-HT in the nucleus tractus solitarius of rats: evidence for functional interactions of neuropeptides and amine neurotransmitters. 241 85

Sixteen patients with endocrine ileal tumors and liver metastases were analyzed with regard to the size, multicentricity, and growth pattern of the primary tumor, the occurrence of carcinoid syndrome, as well as the concentrations of serotonin and substance P (SP) in blood, 5-hydroxy-indole-acetic acid (5-HIAA) in urine, and the course of the disease. Excised specimens from the tumors were immediately processed for immunocytochemical investigations of the presence of neurohormonal peptides, using a broad spectrum of antisera and optimal histoprocessing techniques. In all patients the serotonin levels in blood and/or the 5-HIAA in urine were high. The SP concentration in plasma was markedly elevated in all but two of the ten patients investigated in this respect. A mixed growth pattern prevailed in the tumors of 7 patients with fatal disease. Serotonin cells were found in all tumors and SP-immunoreactive tumor cells in all but one; one of the carcinoids also contained a few tumor cells displaying enkephalin immunoreactivity. In conventionally fixed and paraffin embedded specimens of the same tumors usually no immunoreactive tumor cells at all could be demonstrated, showing that SP is among the peptides vulnerable to poor histotechniques. Nevertheless, SP, together with serotonin, constitute reliable clinical tumor markers for ileal carcinoids.
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PMID:Endocrine tumors of the ileum. Cytochemical and clinical aspects. 241 56

Intracellular recordings were made from guinea-pig myenteric neurons in tissue culture. The responses to substance P (SP) and serotonin were compared. Putative transmitters were ejected by pressure from micropipettes. The response to SP was, in the majority of cases, a prolonged depolarization, with a latency of 1-5 s and a duration of 1-2 min. During the depolarization there was an increase in the input resistance of the cells, and the excitability was augmented. In two neurons the response to SP was hyperpolarization followed by depolarization. In about 30% of the cells the response to SP was relatively fast, with a duration of less than 10 s and a latency of less than 100 ms. These responses did not show desensitization. Serotonin induced relatively fast responses only, with durations of 0.3-3 s and latencies of 20-50 ms. These responses were usually depolarizing, but in 3 cells were hyperpolarizing. Two types of behaviour were observed during repetitive ejection of serotonin. Some cells showed strong desensitization while in others there was no desensitization and there was even summation. The actions of SP and serotonin were compared by their ejection in the same experiments. The same general properties described above were observed. It is concluded that the two putative transmitters act via distinct response mechanisms. The SP-induced depolarizations in tissue culture resemble in several respects the slow synaptic potentials recorded previously in myenteric neurons in freshly isolated preparations.
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PMID:The actions of substance P and serotonin on myenteric neurons in tissue culture. 241 86

Vagal nerve stimulation caused a release of substance P (SP) and serotonin (5-HT) into the feline portal circulation. Both substances are gut spasmogens and were demonstrated in gut nerves by immunocytochemistry. In anesthetized cats gastric and pyloric motility were studied simultaneously at stimulation with SP or 5-HT via the splenic artery or at stimulation of the extrinsic nerves to evaluate their role in the motor control of these regions. The vagally induced pyloric contraction was noncholinergic and nonadrenergic but sensitive to hexamethonium in contrast to the cholinergic gastric contraction, which was resistant to ganglionic blockade. Splanchnic nerve stimulation caused relaxatory gastropyloric responses; the gastric relaxation was sensitive to adrenergic or ganglionic blockade in contrast to the pyloric relaxation. Infrequent contractile responses were seen, which were antagonized by atropine. Injection of SP via the splenic artery elicited contractile gastropyloric responses, which were sensitive to atropine and an antagonistic SP-analogue (SPA) but resistant to hexamethonium, indicating SP activating a final cholinergic neuron. The vagally induced pyloric contraction was resistant to atropine but sensitive to SPA and hexamethonium, indicating involvement of SP in the activation of preganglionic neurons as well. Involvement of SP in a vagal afferent mechanism is possible, since heat activation of the distal end of the divided vagal nerve induced a gastric contraction, sensitive to atropine and SPA but not to ganglionic blockade, indicating antidromic activation of SP afferents which via axon collaterals excite cholinergic neurons. A regional difference between stomach and pylorus was suggested by the different motor responses after pharmacological blockade, heat-activation or i.a. injection of capsaicin. The contractile pyloric responses to 5-HT were antagonized by peripheral blockade of 5-HT2 receptors. However, such blockade did not influence the motor responses to extrinsic nerve stimulation, suggesting that 5-HT is not essential for the mediation of these responses. The contractile responses to SP or 5-HT were studied in vitro in antral and pyloric strips from the rat. These responses were antagonized by SPA or SP tachyphylaxis and peripheral blockade of 5-HT2 receptors respectively. The responses were not reduced by tetrodotoxin, indicating main activation of muscular receptors. However, the contractile responses were reduced by atropine or hexamethonium, except the SP-induced pyloric contraction, which was atropine-sensitive but hexamethonium-resistant.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:On the role of substance P and serotonin in the pyloric motor control. An experimental study in cat and rat. 241 34


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