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 developing fetal monkey visual cortex was studied immunocytochemically from 110-155 days post-conception in order to localize cell populations immunoreactive (ir) for gamma-aminobutyric acid, Substance P, cholecystokinin-octapeptide, somatostatin, neuropeptide Y, and proenkephalin A peptide (BAM-18). The area 17/18 border and all cortical laminae identified in the adult visual cortex were discernible from the youngest age examined. All ir-cell populations studied were present at each fetal age. However, despite a relatively adult-like cytoarchitecture, all ir-cell populations studied displayed patterns of immunostaining which were unlike those described in adult visual cortex, and showed significant changes in laminar distribution, morphology, and numbers over the time course of gestation examined. Despite the differences in the patterns of immunostaining between the fetal and adult visual cortex, ir-cell populations intrinsic to the developing visual cortex exhibited adult-like combinations of co-localized transmitters and peptides. The developing monkey cortex also contains ir-cell populations, particularly BAM-18-ir cells, which have not been detected immunocytochemically in the adult monkey cortex. Differences between the fetal and the adult ir-cell populations might be accounted for by cell death, morphological transformation, secondary migration or changes in gene expression for neurotransmitters and neuropeptides.
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PMID:Temporal sequence of neurotransmitter expression by developing neurons of fetal monkey visual cortex. 246 14

These experiments examined the effects of intrathecally administered gamma-aminobutyric acid (GABA) agonists on the effects of intrathecally administered excitatory amino acid (EAA) agonists: N-methyl-D-aspartic acid (NMDA), quisqualic acid and kainic acid. We have found that muscimol, a GABAA receptor agonist, but not baclofen, a GABAB receptor agonist, dose-dependently inhibited caudally directed biting and scratching behavior induced by all three EAA agonists. This nonselective blockade of the expression of effects mediated by all three types of EAA receptor is in marked contrast to the selective blockade of NMDA effects seen previously in the case of mu opioids and phencyclidine receptor agonists. Inhibition by muscimol was blocked with the GABAA receptor antagonist, bicuculline. Decreased latency or hyperalgesia in the tail-flick test, found previously to be induced selectively by NMDA and blocked by an NMDA receptor antagonist, was similarly affected by muscimol but not baclofen, each given intrathecally. However, muscimol prolonged the tail-flick latency only after presentation of NMDA suggesting a possible antinociceptive effect of GABAA agonists in the presence of agonists at NMDA receptors. This study together with the preceding paper resolves GABA-mediated spinal antinociception into two components: a GABAA agonist selectively blocks nociception involving EAA receptors whereas a GABAB agonist selectively blocks substance P spinal activity (the preceding paper).
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PMID:Muscimol, gamma-aminobutyric acidA receptors and excitatory amino acids in the mouse spinal cord. 246 78

The organization of neuroactive substances in the rat lateral geniculate body (LGB) was studied with available immunohistochemical stainings. In the dorsal lateral geniculate nucleus (DLG), there existed only gamma-aminobutyric acid (GABA)-like immunoreactive neurons. Immunoreactive fiber plexuses for substance P (SP), cholecystokinin-8 (CCK) and vasoactive intestinal polypeptide (VIP) were present in the lateral margin of the DLG, just beneath the optic tract. There were immunoreactive neurons and fibers for GABA, SP, leucine-enkephalin (ENK) and neuropeptide Y (NPY) in the intergeniculate leaflet (IGL). ENK-, NPY- and SP-like immunoreactive neurons in the IGL were mainly medium-sized, and bipolar or spindle-shaped with a few dendrites oriented dorsoventrally. In the IGL, use of double-labeled immunofluorescence demonstrated that a few neurons exhibited both ENK- and SP-like immunoreactivities, and a few neurons had both GABA- and ENK-like immunoreactivities. Although the morphology of ENK-like immunoreactive neurons resembled to NPY-like immunoreactive neurons, both neurons were clearly different neurons. Many GABA-, ENK- and SP-like immunoreactive neurons and fibers were found in the ventral lateral geniculate nucleus (VLG). These immunoreactive neurons were mainly medium-sized, and bipolar in shape, while a few immunoreactive neurons were of multipolar shape. Neurons containing ENK and fibers containing SP mainly existed in the lateral half of the parvocellular part and in the medial half of magnocellular part of the VLG. In this region, about one-third of the GABA-like immunoreactive neurons contained ENK-like immunoreactivity. Many SP neurons mainly existed in the medial half of the parvocellular part of the VLG. CCK- and VIP-like immunoreactive fibers were present in the lateral half of the magnocellular part of the VLG. Immunoreactive fibers for calcitonin gene-related peptide, corticotropin-releasing factor, neurotensin and tyrosine hydroxylase were disseminated throughout the LGB. The subdivisions of the LGB were discussed, based upon the distribution of neuroactive substances.
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PMID:The organization of the rat lateral geniculate body by immunohistochemical analysis of neuroactive substances. 246 11

The responses to excitatory and inhibitory amino acids and peptides were investigated in isolated rat spinal dorsal horn neurons (laminae I-V) of young rats using the whole-cell voltage-clamp technique. The treatment of spinal slices with low concentrations of enzymes and mechanical dissociation yielded isolated neurons that were sensitive to excitatory amino acids (glutamate, kainate, quisqualate and N-methyl-D-aspartate (NMDA), inhibitory amino acids (gamma-aminobutyric acid (GABA), glycine) and peptides (substance P, calcitonin gene-related peptide (CGRP). The responses of dorsal horn neurons to NMDA were potentiated by glycine and CGRP, whereas GABAA responses were enhanced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Our observations indicate that there is reasonable agreement between many of the responses of isolated neurons and those studied in in vivo and in vitro slice and culture preparations.
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PMID:Excitatory and inhibitory amino acids and peptide-induced responses in acutely isolated rat spinal dorsal horn neurons. 247 93

1. Evidence suggests that gamma-aminobutyric acid (GABA) and its receptors are present in the peripheral nervous system. We have now investigated the effect of GABA and related substances on non-adrenergic, non-cholinergic (NANC) neurally-evoked bronchoconstriction in the anaesthetised guinea-pig. 2. Bilateral vagal stimulation (5 V, 5 ms, 3 or 5 Hz) for 30 s, after propranolol (1 mg kg-1 i.v.) and atropine (1 mg kg-1 i.v.) evoked a NANC bronchoconstrictor response manifest as a mean tracheal pressure rise of 21.9 +/- 1.04 cmH2O (n = 70). The bronchoconstrictor response was reproducible for any given animal. 3. GABA (10 micrograms-10 mg kg-1 i.v.) did not alter basal tracheal pressure but reduced the NANC bronchoconstrictor response to vagal stimulation in a dose-dependent manner (ED50 = 186 micrograms kg-1 with a maximal inhibition of 74 +/- 3.4% at 10 mg kg-1). Neither the opioid antagonist naloxone (1 mg kg-1 i.v.) nor the alpha-adrenoceptor antagonist phentolamine (2.5 mg kg-1 i.v.) had any significant effect on the inhibitory response produced by GABA (500 micrograms kg-1). 4. GABA-induced inhibition was not antagonised by the GABAA-antagonist bicuculline (2 mg kg-1 i.v.). 5. The GABAB-agonist baclofen (10 micrograms-3 mg kg-1 i.v.) caused a dose-dependent inhibition of the NANC response (ED50 = 100 micrograms kg-1 with a maximal inhibition of 35.5 +/- 2.8% at 3 mg kg-1). The GABAA-agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-C] pyridin-3-ol (THIP), also inhibited the NANC bronchoconstrictor response. However, the dose of THIP required for this effect was high (3 mg kg- ') and the effect ( <10% inhibition) was small. 6. Substance P (SP; 5upgkg-1 or 25pgkg-1), produced a bronchoconstrictor response equivalent to that produced by NANC vagal stimulation. This response was significantly increased by injection of GABA. Baclofen had no significant effect on responses evoked by exogenous SP. 7. We conclude that GABA inhibits the release of transmitter from NANC nerves via an action at GABAB receptors and that GABA might play a role in the regulation of neurogenic responses in the airways.
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PMID:Modulation of non-adrenergic, non-cholinergic neural bronchoconstriction in guinea-pig airways via GABAB-receptors. 247 4

Ulex europaeus agglutinin I (UEA-I) is a plant lectin with an affinity for L-fucosyl residues in the chains of lactoseries oligosaccharides associated with medium- and smaller-diameter dorsal root ganglion neurons and their axonal processes. These enter Lissauer's tract and terminate within the superficial laminae of the spinal cord overlapping projections known to have a nociceptive function. This implies that the surface coatings of neuronal membranes may have a relationship with functional modalities. The present investigation further examined this concept by studying a neuronal projection with a nociceptive function to determine whether fucosyl-lactoseries residues were incorporated in its primary afferent terminals. Transganglionic transport of horseradish peroxidase (HRP) following injection into tooth pulp chambers was employed to demonstrate dental pulp terminals in the trigeminal spinal complex, while peroxidase and fluorescent tags were used concomitantly to stain for UEA-I. Double immunolabeling for substance P (SP) and gamma-aminobutyric acid (GABA) using peroxidase and colloidal gold allowed a comparison of the distribution of a known excitatory nociceptive transmitter with that of UEA-I binding in specific subnuclei. Synaptic interrelationships between UEA-I positive dental pulp primary afferent inputs and specific inhibitory terminals were also examined. SP immunoreactivity occurred in laminae I and outer lamina II (IIo) of subnucleus caudalis (Vc) and in the ventrolateral and lateral marginal region of the caudal half of subnucleus interpolaris (Vi), including the periobex area in which Vi is slightly overlapped on its lateral aspect by cellular elements of Vc. The adjacent interstitial nucleus (IN) also showed an intense immunoreactivity for this peptide antibody. UEA-I binding displayed a similar distribution pattern in both Vc and Vi, but extended into lamina IIi and the superficial part of Lamina III in Vc. Dental pulp terminals were found to have a comparable distribution; however, many extended into the dorsal portion of the caudal half of Vi and the ventromedial quadrant of rostral Vi. Electron-microscopic analysis showed that transganglionically labeled dental pulp terminals contained ovoid, complex membrane-bound vacuoles laden with transported HRP. The preterminal axon and synaptic membranes of those dental pulp terminals located in zones of Vc and Vi displaying an affinity for UEA-I were usually characterized by a patchy, electron-dense coating of the peroxidase tag. SP was demonstrated ultrastructurally with Protein-A colloidal gold (3-nm particles), whereas GABA immunoreactivity was revealed by the avidin-biotin-peroxidase method.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ulex europaeus agglutinin-I binding to dental primary afferent projections in the spinal trigeminal complex combined with double immunolabeling of substance P and GABA elements using peroxidase and colloidal gold. 247 97

Cerebrospinal fluid (CSF)-contacting neurons are located periventricularly or inside the brain ventricles; they contact the CSF via their dendrites, perikarya or axons. Most of these neurons form ciliated dendrite terminals in the internal CSF as do retinal and pineal photoreceptors in the optic ventricle and pineal recess. The peculiar localization, polarization and synaptic connections of the CSF-contacting neuronal elements suggest receptor and integrative functions. The present review pays special attention to vitamin A (retinoids) immunoreactivity in CSF-contacting neurons as compared with that present in retinal and pineal photoreceptor cells, common neurons, glial and adenohypophysial cells. The immunoreactivity of the dark-adapted photoreceptor outer segments was strong, but decreased after illumination, suggesting the functioning of vitamin A as the chromophore of the retinal and pineal photopigments. Retinoid immunoreaction was also found in the endoplasmic reticulum, nuclei, nucleoli and mitochondria of the cell types studied. This cytological localization suggests that vitamin A compounds may be involved in the function of these organelles. The CSF-contacting neurons contain varying amounts of bioactive materials. The intracellular distribution of immunoreactive serotonin (5-HT), substance P (SP) and gamma-aminobutyric acid (GABA) is compared with that of immunoreactive vitamin A. Immunogold labeling for SP was demonstrated in dense-core vesicles of preoptic neurons; 5-HT marking was found on the dense-core vesicles of subependymal CSF-contacting neurons of the paraventricular organ, while GABA immunoreaction was localized in the cytoplasm of distal infundibular CSF-contacting neurons. The CSF-contacting neurons are considered to synthesize and release their bioactive substances at transmitter synapses, and/or at neurohormonal terminals into the external CSF in accord with information received by their dendrites from the internal CSF and by afferent fiber connections from various brain areas.
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PMID:The cerebrospinal fluid-contacting neuron: a peculiar cell type of the central nervous system. Immunocytochemical aspects. 247 2

1. An isolated spinal cord-peripheral nerve preparation of the newborn rat was developed. In this preparation it is possible to record spinal reflexes from a lumbar ventral root in response to stimulation of the ipsilateral saphenous or obturator nerve. 2. Single shock, weak intensity stimulation of the saphenous nerve induced a fast conducted compound action potential in the L3 dorsal root and a fast depolarizing response in the ipsilateral L3 ventral root. As a stronger stimulus was applied to the saphenous nerve, a slowly conducted compound action potential appeared in the dorsal root and a slow depolarizing ventral root potential (v.r.p.) in the L3 ventral root. 3. Single shock stimulation of the obturator nerve induced a rapidly conducted compound action potential in the L3 dorsal root and monosynaptic and polysynaptic reflexes, with a fast time course, in the ipsilateral L3 ventral root. 4. The slow v.r.p. evoked by saphenous nerve stimulation was depressed by the tachykinin antagonist, [D-Arg1, D-Trp7,9, Leu11] substance P (spantide), 4-16 microM. The response recovered its original shape and size 30-60 min after the removal of this antagonist. 5. The saphenous nerve-evoked slow v.r.p. was depressed by [Met5] enkephalin (0.1-1 microM), dynorphin (1-13)(0.2 microM) and morphine (1-2 microM), and these effects were reversed by naloxone (1 microM). 6. Two endogenous peptides, galanin (1-2 microM) and somatostatin (1-2.5 microM), inhibited the slow v.r.p. evoked by saphenous nerve stimulation, whereas another endogenous peptide, calcitonin gene-related peptide (0.1-0.5 microM), potentiated the slow v.r.p. The slow v.r.p. was also inhibited by gamma-aminobutyric acid (GABA, 20 microM) and muscimol (0.2 microM), and their effects were antagonized by bicuculline (1 microM). 7. The present results suggest that substance P and neurokinin A are involved in the saphenous nerve-evoked C-fibre response in the spinal cord of the newborn rat.
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PMID:Pharmacological properties of a C-fibre response evoked by saphenous nerve stimulation in an isolated spinal cord-nerve preparation of the newborn rat. 247 38

1. The action of substance P (SP) on the release of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) and on contraction were studied in strips of the guinea-pig urinary bladder. Substance P induced a dose-dependent contraction of strips of guinea-pig urinary bladder (EC50 = 1.2 x 10(-9) M). This contraction was not altered by tetrodotoxin, but with a dose of 10(-9) M and less, there was a complete inhibition by 10(-6) M) atropine. Contractions initiated by 3 x 10(-9) M) SP or more were partly inhibited by atropine. The EC50 value of substance P in the presence of atropine was 7.0 x 10(-9) M. 2. Substance P induced a Ca2+-dependent and tetrodotoxin-resistant release of [3H]-acetylcholine (ACh) from strips of urinary bladder preloaded with [3H]-choline (EC50 = 4.9 x 10(-10) M), and this release was antagonized by [D-Pro2,D-Trp7,9] substance P. 3. Bicuculline increased the substance P-induced contraction and the release of [3H]-ACh from the strips. 4. Substance P induced a Ca2+-dependent and tetrodotoxin-sensitive release of [3H]-gamma-aminobutyric acid (GABA) from strips preloaded with [3H]-GABA (EC50 = 2.6 x 10(-9) M), and this release was antagonized by [D-Pro2,D-Trp7,9] substance P. 5. Therefore, substance P appears to exert excitatory effects on the contractility of urinary bladder predominantly by stimulating its own receptor located on the cholinergic nerve terminals. GABA released by substance P inhibits stimulation of the cholinergic neurone. However, the direct action of substance P on the cholinergic neurone is more potent that the indirect action via GABA release.
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PMID:Regulation of the substance P-induced contraction via the release of acetylcholine and gamma-aminobutyric acid in the guinea-pig urinary bladder. 247 40

Intra-arterial administration of substance P (0.1-50 micrograms/kg) to the urinary bladder of the cat produced slow-onset and sustained bladder contractions, asynchronous firing of bladder postganglionic nerves, and facilitation of nicotinic transmission in bladder ganglia. Intracellular recording from bladder ganglia in vitro revealed that substance P depolarized ganglion cells and initiated burst of action potentials (maximal frequency 6-7 Hz). The ganglionic excitatory effect of substance P in situ was blocked by gamma-aminobutyric acid (2-20 micrograms/kg) and the substance P antagonist [D-Arg1,D-Pro2,D-Trp7.9,Leu11]substance P (0.5-20 micrograms/kg) but was not altered by atropine (10-100 micrograms/kg), hexamethonium (0.5-2 mg/kg), norepinephrine (2-20 micrograms/kg), or leucine enkephalin (0.5-20 micrograms/kg). The bladder contractions elicited by substance P were not blocked by atropine, hexamethonium, or [D-Arg1,D-Pro2,D-Trp7.9,Leu11]substance P (0.1-10 micrograms/kg) but were blocked by another substance P antagonist, [D-Pro2,D-Phe7,D-Trp9]substance P. These data indicate that substance P has a direct postsynaptic excitatory effect on neurons in the vesical parasympathetic ganglia and on bladder smooth muscle cells. The differential effects of substance P antagonists on the excitatory responses at these two sites indicate the responses were mediated by different types of tachykinin receptors.
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PMID:Excitatory effect of substance P in parasympathetic ganglia of cat urinary bladder. 248 6


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