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)

Subpopulations of raphe pallidus (Rpa) and raphe obscurus (Rob) neurons containing TRH, serotonin (5-HT), and substance P contribute projections to the dorsal vagal complex (DVC). Activation of Rpa and Rob neurons induces a vagal cholinergic-dependent stimulation of gastric secretory and motor function and modulates resistance of the gastric mucosa to gastric injury in rats and cats. The caudal raphe nuclei-DVC pathways containing TRH/5-HT are involved in mediating cold-induced vagal stimulation of gastric function and erosion formation. These results suggest that Rpa/Rob-DVC projections containing TRH/5-HT may be an important pathways in the medullary regulation of vagal activity to the viscera.
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PMID:Caudal raphe-dorsal vagal complex peptidergic projections: role in gastric vagal control. 754 64

Parasympathetic preganglionic neurons in the superior salivatory nucleus (SSNNs) projecting to the pterygopalatine ganglion were labeled by retrograde transport of cholera toxin B subunit (CTB) in the rat. Morphological interactions between SSNNs and afferent fibers immunoreactive (IR) for neuropeptide and amine were examined with light and electron microscopes by double-immunostaining techniques. SSNNs were found in the ipsilateral ventrolateral part of the rostral medulla oblongata. Around SSNNs, substance P-, enkephalin-, neuropeptide Y-and somatostatin-IR nerve fibers were very rich and tyrosine hydroxylase (TH)-, serotonin (5-HT)-, vasoactive intestinal polypeptide- and calcitonin gene-related peptide (CGRP)-IR axons showed moderate density. Thyrotropin-releasing hormone-containing axons were scarce in this region. The electron microscopic examinations revealed that CTB-IR structures directly received synaptic input from axon varicosities IR for TH, 5-HT and all neuropeptides except for CGRP. These findings suggest that catecholamine, 5-HT and the neuropeptides directly influence the activity of SSNNs and are concerned with the autonomic regulation of nasal and palatal mucosa, lacrimal glands and cerebral blood vessels of the rat.
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PMID:Synaptic contact of neuropeptide-and amine-containing axons on parasympathetic preganglionic neurons in the superior salivatory nucleus of the rat. 758 52

The present study was designed to investigate the effects of centrally administered neuropeptides on the discriminative stimulus properties of cocaine in the rat. Rats were trained to discriminate 10.0 mg/kg of cocaine from vehicle in a shock avoidance paradigm. The mu-selective opioid agonist [D-Ala2,NMePhe4,Gly-ol]enkephalin (DAMGO) (0.03-0.3 microgram, ICV) or the kappa-selective opioid agonist dynorphin A-(1-13) (1.0-10.0 micrograms, ICV) did not generalize to cocaine cue, although the delta-selective opioid agonist [D-Pen2,L-Pen5]enkephalin (DPLPE) (10.0 micrograms, ICV) reportedly generalizes to it through the mediation of delta-opioid receptors. Thyrotropin-releasing hormone (10.0-56.0 micrograms, ICV), somatostatin (0.3-3.0 micrograms, ICV), substance P (3.0-17.5 micrograms, ICV), or neurotensin (3.0-17.5 micrograms, ICV) did not produce any stimulus effects in common with cocaine. It appears that neuropeptides other than the delta-selective opioid do not play a major role in the discriminative stimulus properties of cocaine.
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PMID:Effects of centrally administered neuropeptides on discriminative stimulus properties of cocaine in the rat. 767 47

In order to test the possible effects of an intravenous administration of substance P (SP) on basal and TRH-stimulated PRL release, SP was infused alone (0.5 or 1.5 pmol/kg-1/min-1 for 60 min) or after TRH (20 or 400 micrograms in an i.v. bolus) in 21 normal male subjects. In addition, plasma cortisol levels during SP infusion were measured. In agreement with previous findings, a significant increase in plasma cortisol levels was observed when the higher (1.5 pmol/kg-1/min-1) but not the lower (0.5 pmol/kg-1/min-1) amount of SP was given. In contrast, basal and TRH (20 or 400 micrograms)-induced PRL release were not modified by SP at any tested amount. These data suggest that, in normal men, plasma SP is not involved in the control of PRL release at the anterior pituitary level.
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PMID:Intravenously infused substance P is unable to change basal and TRH-stimulated PRL secretion in normal men. 769 3

The topographical distribution of neuropeptide-containing cell bodies, fibers and terminals was studied in the premamillary region of the rat hypothalamus using light microscopic immunohistochemistry. Alternate coronal sections through the posterior third of the hypothalamus of normal and colchicine-treated male rats were immunostained for 19 different neuropeptides and their distributions were mapped throughout the following structures: the ventral and dorsal premamillary, the supramamillary, the tuberomamillary and the posterior hypothalamic nuclei, as well as the premamillary portion of the arcuate nucleus and the postinfundibular median eminence. Seventeen of the investigated neuropeptides were present in neuronal perikarya, nerve fibers and terminals while the gonadotropin associated peptide and vasopressin occurred only in fibers and terminals. Growth hormone-releasing hormone-, somatostatin-, alpha-melanocyte stimulating hormone-, adrenocorticotropin-, beta-endorphin- and neuropeptide Y-immunoreactive neurons were seen exclusively in the premamillary portion of the arcuate nucleus. Thyrotropin-releasing hormone-, dynorphin A- and galanin-containing neurons were distributed mainly in the arcuate and the tuberomamillary nuclei. A high number of methionine- and leucine-enkephalin-immunoreactive cells were detected in the arcuate and dorsal premamillary nuclei, as well as in the area ventrolateral to the fornix. Substance P-immunoreactive perikarya were present in very high number within the entire region, in particular in the ventral and dorsal premamillary nuclei. Cell bodies labelled with cholecystokinin- and calcitonin gene-related peptide antisera were found predominantly in the supramamillary and the terete nuclei, respectively. Corticotropin-releasing hormone-, vasoactive intestinal polypeptide- and neurotensin-immunoreactive neurons were scattered randomly in low number, mostly in the arcuate and the ventral and dorsal premamillary nuclei. Peptidergic fibers were distributed unevenly throughout the whole region, with each peptide showing an individual distribution pattern. The highest density of immunoreactive fibers was presented in the ventral half of the region including the arcuate, the ventral premamillary and the tuberomamillary nuclei. The supramamillary nucleus showed moderately dense fiber networks, while the dorsal premamillary and the posterior hypothalamic nuclei were poor in peptidergic fibers.
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PMID:Immunohistochemical mapping of neuropeptides in the premamillary region of the hypothalamus in rats. 779 57

Substance P and the two other mammalian tachykinins, neurokinin A and B, are accepted to have direct regulating effects at the anterior pituitary level. We have examined the effects of substance P (SP) and neurokinin B (NKB), alone and in combination, on prolactin release from cultured anterior pituitary cells grown on collagen-coated micro beads and placed in a perfusion system. Prolactin (Prl) secretion was observed within 25 s after exposure to either secretagogue and reached a maximum within 60-80 s. Furthermore, the prolactin response induced by SP and NKB was dose-dependent. Prl secretion remained constant for up to 4 h when SP or NKB were perifused and then fell gradually towards basal levels. Simultaneous addition of submaximal concentrations of SP and NKB resulted in an additive response compared with the responses of either secretagogue alone. Continuous (8 h) perifusion with SP did not prevent a normal prolactin response by NKB or TRH. These results indicate that the tachykinins, substance P and neurokinin B, release Prl from perifused female rat anterior pituitary cells by interaction with two different receptors, possibly the NK1 and NK3 tachykinin receptor subtypes.
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PMID:Tachykinins induce secretion of prolactin from perifused rat anterior pituitary cells by interactions with two different binding sites. 890 62

Prolyl endopeptidase has been predominantly described as a cytosolic activity capable of cleaving a number of important neuropeptides (including TRH, LHRH, Bradykinin, Angiotensin, Substance P, Neurotensin, Oxytocin and Vasopressin) on the carboxy side of proline. In this paper, we report, for the first time, on the complete purification and characterization of a membrane-bound form of prolyl endopeptidase. This novel activity has been isolated from the synaptosomal (plasma membranes) membranes of bovine brain. Following gel filtration, hydroxylapatite and hydrophobic interaction chromatographies, the prolyl endopeptidase activity was purified 1400-fold with a 23% recovery of activity. The enzyme was shown to have a relative molecular mass of 87 kDa and a Km of 60 microM for its specific fluorimetric substrate, Z-GlyProMCA. The purified enzyme demonstrated a relatively broad substrate specificity and a relatively high affinity for proline-containing neuropeptides. It was shown to be inhibited by certain thiol-protease inhibitors and by the metal chelator, 1,10-phenanthroline, thus possibly classifying it as a 'thimet' activity. The purified particular form of proyl endopeptidase displayed a similar substrate specificity to the previously reported cytosolic forms of the enzyme. However, there were differences between the two forms in term of their sensitivity to inhibitors, their affinities for the peptide substrates and their relative molecular masses. The different subcellular location (i.e. the synaptosomal membrane) of the particulate prolyl endopeptidase is also of potential physiological significance given that here it is more likely to come in contact with the vesicle-bound neuropeptides than is its cytosolic counterpart.
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PMID:Purification and characterization of a novel membrane-bound form of prolyl endopeptidase from bovine brain. 902 55

Using whole-cell patch-clamp techniques, we show that oligosphere-derived oligodendrocyte progenitor cells (OP) display GABA-, glutamate-, 5-HT-, glycine- and acetylcholine-gated inward currents. When OP differentiate into oligodendrocytes (ODC), the amplitude of peak currents elicited by saturating concentrations of these transmitters decreases except for 5-HT. Intracellular Ca2+ concentration changes induced by microperfusion of glutamate, 5-HT, TRH, met-enkephalin and substance P were monitored using a fluo-3-based calcium imaging system. When OP cells differentiate into ODC, a global decrease of the proportion of responding cells is observed. During type-2 astrocytes commitment, this proportion decreases for 5-HT, TRH- and metenkephalin stimulations whereas it remains constant for substance P and glutamate. These data demonstrate a development regulation of neurotransmitter- and neuropeptide-induced responses within the oligodendroglial lineage.
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PMID:Developmental regulation of neuroligand-induced responses in cultured oligodendroglia. 960 52

Inhibition of "leak" potassium (K+) channels is a widespread CNS mechanism by which transmitters induce slow excitation. We show that TASK-1, a two pore domain K+ channel, provides a prominent leak K+ current and target for neurotransmitter modulation in hypoglossal motoneurons (HMs). TASK-1 mRNA is present at high levels in motoneurons, including HMs, which express a K+ current with pH- and voltage-dependent properties virtually identical to those of the cloned channel. This pH-sensitive K+ channel was fully inhibited by serotonin, norepinephrine, substance P, thyrotropin-releasing hormone, and 3,5-dihydroxyphenylglycine, a group I metabotropic glutamate receptor agonist. The neurotransmitter effect was entirely reconstituted in HEK 293 cells coexpressing TASK-1 and the TRH-R1 receptor. Given its expression patterns and the widespread prevalence of this neuromodulatory mechanism, TASK-1 also likely supports this action in other CNS neurons.
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PMID:TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons. 1071 94

Substance P (SP) may participate as a paracrine and/or autocrine factor in the regulation of anterior pituitary function. This project studied the effect of TRH on SP content and release from anterior pituitary and the role of SP in TRH-induced prolactin release. TRH (10(-7) M), but not vasoactive intestinal polypeptide (VIP), increased immunoreactive-SP (ir-SP) content and release from male rat anterior pituitary in vitro. An anti-prolactin serum also increased ir-SP release and content. In order to determine whether intrapituitary SP participates in TRH-induced prolactin release, anterior pituitaries were incubated with TRH (10(-7) M) and either WIN 62,577, a specific antagonist of the NK1 receptor, or a specific anti-SP serum. Both WIN 62,577 (10(-8) and 10(-7) M) and the anti-SP serum (1:250) blocked TRH-induced prolactin release. In order to study the interaction between TRH and SP on prolactin release, anterior pituitaries were incubated with either TRH (10(-7) M) or SP, or with both peptides. SP (10(-7) and 10(-6) M) by itself stimulated prolactin release. While 10(-7) M SP did not modify the TRH effect, 10(-6) M SP reduced TRH-stimulated prolactin release. SP (10(-5) M) alone failed to stimulate prolactin release and markedly decreased TRH-induced prolactin release. The present study shows that TRH stimulates ir-SP release and increases ir-SP content in the anterior pituitary. Our data also suggest that SP may act as a modulator of TRH effect on prolactin secretion by a paracrine mechanism.
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PMID:Interaction between substance P and TRH in the control of prolactin release. 1092 26


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