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

A pharmacological study was made of the effects of various muscarinic and nicotinic agonists and their antagonists on the release of [3H]noradrenaline ([3H]NA) from cultures of isolated bovine adrenal medullary cells. A study was also made of the effects of substance P and somatostatin on the release of [3H]NA evoked by nicotinic agonists. By 2 days in culture these adrenal 'paraneurons' had developed long varicose processes with growth cones and generally resembled noradrenergic neurons in culture. In the present study, adrenal paraneurons were incubated with [3H]NA which was taken up and stored in reserpine-sensitive sites. Exposure of the cultures to acetylcholine (ACh) resulted in release of [3H]NA into the external medium. High concentrations of K+ (56 mM) also evoked release of [3H]NA. The release of [3H]NA induced by ACh or K+ (56 mM) was Ca2+-dependent. Pharmacological studies with nicotinic (ACh, nicotine) and muscarinic (methacholine, pilocarpine) agonists and their antagonists (mecamylasmine, d-tubocurarine, hexamethonium; and atropine, scopolamine, respectively) showed that the adrenal paraneurons contained only nicotinic receptors. Substance P produced a dose-dependent inhibition of ACh (5 x 10(-5) M) stimulated [3H]NA release in the range of 10(-8) to 5 x 10(-5) M with an ID50 of 10(-6) M. A similar inhibition of NA release by substance P was obtained when nicotine (K X 10(-6) M) was used as the agonist, but not when K+ (50 MM) was used to depolarize the cells. Substance P (10-10) to 5 x 10(-5) M) by itself did not have a significant effect on the basal release rate of [3H]NA from these cells. Somatostatin at relatively high concentrations (10(-6)-10(-3) M; ID50 2 x 10(-5) M) inhibited the release induced by ACh, but not by K+ (56 mM). The present results provide the first direct evidence at a cellular level that substance P and somatostatin act as inhibitory modulators of the nicotinic ACh response, and support a role for these peptides as inhibitory neuromodulators at nicotinic receptor sites in the nervous system.
Brain Res 1979 Dec 14
PMID:Pharmacological characterization of adrenal paraneurons: substance P and somatostatin as inhibitory modulators of the nicotinic response. 50 17

An adenocarcinoma of the second portion of the duodenum in a 26-year-old male is presented. The patient was suffering from pain in the epigastrium. Immunofluorescent studies revealed that it consisted almost exclusively of cells with a distincly positive somatostatin-like immunoreactivity. Ultrastructurally, the cytoplasm of the tumor cells had numerous large round granules (about 400 micrometers) with variable electron density. Most of these cells closely resembled the D cells normally seen in the duodenum and the islets of the pancreas, although a few argyrophil cells could be demonstrated by light microscopy. Radioimmunoassay of extracts of the tumor revealed a large amount of somatostatin (2260 pg/mg); substance P and VIP were detected also. Somatostatinoma has been known to occur in the pancreas, but this seems to be the first somatostatinoma found in the intestine.
Cancer 1979 Dec
PMID:Somatostatinoma of the duodenum. 50 96

1. Rat brain synaptosomes were incubated under different conditions to study the release of substance P (SP). 2. Potassium ions and electrical field stimulation induced a loss of SP from synaptosomes. The release of SP by potassium in high concentrations (23.8 mM) was shown to be calcium dependent. 3. Substance P was retained in synaptosomes during incubation in 0.32 M sucrose at +4 degrees C up to 120 min. During incubation at 30 degrees C the SP content fell initially (30 min) but was gradually restored (120 min). 4. If these pre-incubated synaptosomes were reincubated for 45 min at 30 degrees C in potassium free Krebs-Ringer-phosphate buffer a further rise in their SP content occurred which was taken as indication that SP is being synthesized in synaptosomes. 5. The newly synthesized SP is presumably stored by binding to phosphatidyl serine until a sudden release is initiated by depolarization.
Naunyn Schmiedebergs Arch Pharmacol 1977 Dec
PMID:Substance P in rat brain synaptosomes. 60 Mar 16

The recent identification and synthesis of the endecapeptide substance P has renewed interest in this naturally occurring compound. The original substance P of Euler and Gaddum was a mixture of biologically active substances, some of which were peptides. The peptide component was responsible for gut-contracting, hypotensive and sialogogic properties attributed to substance P. For almost 40 years following its discovery, substance P resisted isolation and purification. Even the most highly active preparations were heterogeneous and there was a divergence of results from experiments using preparations which were partially purified by different techniques. Nevertheless much of the early work on the distribution and pharmacology of crude substances P has been confirmed using the synthetic endecapeptide and has stimulated research towards the elucidation of a possible functional role for substance P. Most proposed functions have been highly speculative but, at present, evidence is accumulating in support of a physiological role for substance P as a neurotransmitter in sensory pathways.
Aust J Exp Biol Med Sci 1977 Dec
PMID:Substance P: its pharmacology and physiological roles. 61 35

Internal carotid artery blood flow was studied by peroperative electromagnetic blood flow measurement in 7 patients following 9 intravenous infusions of synthetic Substance P, 2 ng.kg-1.min-1. The blood flow responses varied interindividually. No significant blood flow changes were observed for the whole group. The arterial mean blood pressure decreased significantly.
Acta Physiol Scand 1978 Dec
PMID:Effect of synthetic substance P on internal carotid artery blood flow in man. 72 41

In the past, substance P (SP) has been suggested to be both an opiate agonist and an antagonist. It therfore seemed appropriate to examine potential interactions of SP and opioids on guinea pig ileum. On non-stimulated ileal strips SP caused a dose responsive increase in contraction. Pretreatment of the tissue with morphine (3, 30, 300, 3000 nM), enkephalin (1.42, 14.2, 142, 1420 nM), naloxone (5nM), or atropine (0.144 micron) did not significantly alter the spasmogenic effect of SP. On stimulated guinea pig ileum, whereas morphine and enkephalin inhibited the electrically induced twitch, SP adminstration resulted in contraction of the tissue. Additionally, neither strongly effective non sub-threshold doses of SP antagonized the effects of the narcotics. These data are discussed in terms of separate receptors mediating the effects of the opiates and SP on guinea pig ileum.
Eur J Pharmacol 1978 Dec 15
PMID:Substance P and opioid interaction on stimulated and non-stimulated guinea pig ileum. 73 56

Substance P is an undecapeptide that is distributed in many areas of the central nervous system. In order to clearly identify the structures and organelles containing substance P, an immunohistochemical localization of this peptide was performed at the ultrastructural level. Substance P was detected in dense core vesicles of many nerve endings in both the amygdaloid nucleus and the substantia gelatinosa of the spinal cord. These findings support the hypothesis that substance P could act as a neurotransmitter.
J Histochem Cytochem 1977 Dec
PMID:Electron microscope immunohistochemical localization of substance P in the central nervous system of the rat. 92 43

Sensitive and specific radioimmunoassay for substance P was developed using synthetic substance P and 125I-Nalpha-tyrosyl-substance P. Substance P-human alpha-globulin conjugate was used for production of anti-substance P antisera in rabbits. Synthetic substance P was used as a standard and the dextran-coated charcoal method was employed to separate the free peptide from that bound to antibodies. No cross-reactions by physalaemin and eledoisin observed in this system proved its high specificity to substance P. Nalpha-Tyrosyl-substance P and [Tyr1]-substance P showed the displacement curves indistinguishable from that of the standard substance P. Neither substance P5-11 nor substance P6-11 competed with the tracer at the concentration used. The minimum measurable dose of substance P by the assay system was 2.5-5 pg/incubate. Utilizing the system, human plasma samples from 42 healthy volunteers of both sexes were shown to contain immunoreactive substance P in amounts that averaged 298 pg/ml in male and 251 pg/ml in female. Substance P-like immunoreactivity was also demonstrated in hot-water extracts of porcine duodenum, jejunum, ileum, cecum, middle colon, rectum, pancreas, stomach and pituitary. The highest concentration (379 ng/g wet weight of organ) was found in the pituitary, and the ileum (7.9 ng/g wet weight of organ) and jejunum (1.9 ng/g wet weight of organ) were rich in the contents.
Endocrinol Jpn 1976 Dec
PMID:Substance P radioimmunoassay using Nalpha-tyrosyl-substance P and demonstration of the presence of substance P-like immunoreactivities in human blood and porcine tissue extracts. 102 20

With the indirect immunofluorescence technique of Coons and collaborators the occurrence of substance P (SP)-like immunoreactivity was studied in spinal ganglia (L6-S1), the spinal cord (L6-S1) and the pad skin of the hind paw of the cat. In untreated cats a very dense network of SP-positive fibers was found in the spinal cord in Lissauer's fasciculus, in laminae I-III and a rather dense plexus was seen in the ventral horns, in the area around the central canal (laminae X) and in the medial parts of laminae VI and VII. SP-positive fibers were also observed in the connective tissue under the epithelium of the skin. However, in untreated cats no specific immunogluorescnece was observed in the spinal ganglia, dorsal roots or certain large peripheral nerve trunks. After certain experimental procedures such as local application of colchicine or compression of the dorsal root close to the spinal ganglion, SP-positive fluorescence was observed in a rather small number of neuronal cell bodies and in fibers. The fluorescent material was observed in the peripheral parts of the cytoplasm and the cell bodies were exclusively of the small type. Ten days after transection of the dorsal roots a marked decrease in the number of SP-positive fibers was observed in the substantia gelatinosa but not in the ventral horns. The present results give strong evidence for the occurrence of SP in a certain population of primary sensory neurons and support earlier findings that SP may act as a transmitter or modulator in these neurons.
Brain Res 1975 Dec 19
PMID:Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons. 110 79

The aim of the study was to test whether the synthesis of substance P (SP) and that of its receptor (also known as NK1 receptor) are coordinately regulated after chronic pharmacologic intervention in two neural systems, the spinal cord and basal ganglia. In one set of experiments, capsaicin was administered subcutaneously during the early postnatal period (day 3 after birth) to induce degeneration of afferent sensory neurons in the spinal cord. In the other set of experiments, interruption of dopaminergic transmission was achieved by two methods: (a) The neurotoxin 6-hydroxydopamine was used to denervate dopaminergic neurons during the early postnatal period, and (b) haloperidol was used in adult animals to block dopaminergic transmission by receptor blockade. The spinal cord, striatum, or both were used for the quantification of tachykinin [SP and neurokinin A (NKA)] and opioid peptides [[Met5]-enkephalin (ME) and dynorphin A (1-8) (DYN)] by radioimmunoassays. The abundance of total SP-encoding preprotachykinin (PPT) mRNA and SP receptor (SPR) mRNA in spinal cord (C5 to T1 segments), striatum, or microdissected substantia nigra was determined by northern blot or solution hybridization analysis. Amines and their acid metabolites were quantified by HPLC. Capsaicin administration (subcutaneously) during the early postnatal period increased latency in a hot-plate test, decreased SP and NKA levels, increased levels of PPT mRNAs, and did not affect SPR mRNA levels in the spinal cord. Intraspinal SP systems may attempt to compensate for the loss of afferent SP input, whereas spinal cord receptor mRNA levels do not appear to be altered.(ABSTRACT TRUNCATED AT 250 WORDS)
J Neurochem 1992 Dec
PMID:Tachykinin systems in the spinal cord and basal ganglia: influence of neonatal capsaicin treatment or dopaminergic intervention on levels of peptides, substance P-encoding mRNAs, and substance P receptor mRNA. 127 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>