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)

Highly specific radioimmunoassays (RIAs) for neurokinin A (NKA) and neurokinin B (NKB) were developed. Antisera were produced by the procedure which involved immunization with NKA or NKB, both conjugated with keyhole limpet hemocyanin, and treatments with a tolerogenic conjugate of kassinin and a copolymer of D-glutamic acid and D-lysine (D-GL) to inhibit the production of cross-reactive antibodies against common C-terminal region of tachykinins. Cross-reactivities of anti-NKA antiserum (R704), thus produced, with NKB, kassinin, eledoisin were 12.6%, 10.6% and 11.5%, respectively. This was in sharp contrast with those of antiserum obtained from the rabbit not treated with kassinin-D-GL, these values corresponding to 129.0%, 42.5% and 94.4%, respectively. The cross-reactivities of R704 with substance P and physalaemin were 0.3% and 1.5%, respectively. This antiserum also bound 35.6% of neuropeptide K which contains NKA at its C-terminal. More importantly, anti-NKB antiserum (R707) obtained by the above tolerizing regimen was highly specific for NKB and the cross-reactivities with NKA, neuropeptide K, kassinin and other tachykinins were all less than 0.001%. RIAs using these specific antisera allowed us to measure directly NKA and NKB in tissue extracts without their fractionation by chromatography prior to RIAs. Measurements of immunoreactive NKA and NKB in different rat brain regions and spinal cord revealed that they are present with various ratios (NKA/NKB: 1.1-9.9) depending on the region.
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PMID:Establishment of highly specific radioimmunoassays for neurokinin A and neurokinin B and determination of tissue distribution of these peptides in rat central nervous system. 254 May 12

[3H]-Flunitrazepam (FNT) binding was measured in the post-mortem brains of 13 chronic schizophrenics and 10 controls whose mean ages and death-to-freezing intervals were the same in each group. The specific binding of [3H]-FNT to the medial frontal cortex, orbitofrontal cortex, orbital cortex, medial and inferior temporal gyri, superior temporal gyrus, cornu Ammonis 1-3 and putamen was significantly higher in schizophrenics than in controls. Specific binding to the eye movement area (frontal eye field), motor cortex, lateral occipitotemporal gyrus, dentate gyrus of the hippocampus and secondary and tertiary visual cortex did not differ in the two groups. Type 1 benzodiazepine (BZ) binding sites in the superior temporal gyrus of schizophrenics, determined from the displacement of [3H]-FNT binding using a triazolopyridazine, CL 218,872 (200 nM), were significantly higher than in the control group. The increase in type 2 BZ binding sites was not significant. Antipsychotic or benzodiazepine medication did not appear to affect the results. There were significant correlations between specific [3H]-FNT binding and concentration of GABA (positive) and of glutamic acid (negative), specific [3H]-kainic acid binding (positive), activity of tyrosine hydroxylase (positive), and substance P-like immunoreactivity (positive) in many areas of the brain. The Bmax of [3H]-spiperone binding in the putamen was also correlated positively with specific [3H]-FNT binding. These data suggest that dysfunction of BZ receptors may be involved in the pathogenesis and some symptoms of chronic schizophrenia.
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PMID:Benzodiazepine receptors increase in post-mortem brain of chronic schizophrenics. 255 17

The roles of putative central neurotransmitters in the control of blood pressure have been reviewed with respect to the cardiovascular functions of individual nerve pathways in the medulla oblongata and spinal cord. Vasomotor activity of sympathetic preganglionic neurones originates from spinally-projecting neurones in the ventrolateral medulla which may include adrenaline neurones of the C1 group and serotonin neurones in the lateral B1 and B3 groups. Other bulbospinal monoamine nerves may modulate vasomotor activity at the spinal level, but the mechanism of this modulation is controversial. Evidence for two descending sympatho-inhibitory pathways has emerged: a noradrenergic projection from the A5 cell group and a serotonergic projection from the medullary raphe (medial B1 and B2 groups). The vasomotor influence of other bulbospinal pathways is unclear. Baroreflex control of blood pressure is mediated through the solitary tract nucleus (NTS). L-Glutamate and substance P are considered as candidates for transmitters in baroreceptor afferents to the NTS. Transmitters in efferent nerves relaying baroreflex activity from the NTS to cardiovagal motoneurones, medullary vasomotor neurones or sympathetic preganglionic neurones have not been identified but the monoamine transmitters present in the NTS appear to modulate baroreflexes. Noradrenaline and serotonin nerve endings may facilitate the vasodepressor component of the baroreflex while adrenaline nerves possibly inhibit the cardiovagal mechanism. Enkephalins and vasopressin act in the NTS to raise blood pressure and nerves containing these neuropeptides may constitute important links in reciprocal cardiovascular pathways between the lower brainstem and hypothalamus.
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PMID:Blood pressure control by neurotransmitters in the medulla oblongata and spinal cord. 286 Jan 49

The purpose of this study was to determine the distribution of cells in the medial reticular formation (MRF) and the pontomedullary locomotor strip (PLS), which can induce locomotion when activated. Controlled microinjections of neuroactive substances (Goodchild et al., 1982) into the MRF or PLS were made in order to activate cell bodies in those areas. The ability of trigeminal receptive field stimulation to induce locomotion before and after drug infusion into the PLS was also assessed since the PLS and the spinal nucleus of the trigeminal nerve are similar in their anatomical distribution. Experiments were performed on precollicular-postmamillary decerebrate cats walking on a treadmill. Injections of glutamic acid (GA; 500 nmol) into the MRF produced locomotion that was antagonized by infusion of glutamic acid diethyl ester into the same spot. Decreases in the current threshold for locomotion produced by electrical stimulation of the MRF were observed when the MRF was infused with either GA (40-80 nmol), DL-homocysteic acid (DL-HCA; 200 nmol), or picrotoxin (PIC; 15 nmol). Injections of GA (100 nmol), DL-HCA (700 nmol), PIC (10-50 nmol), and substance P (2 nmol) into the PLS also produced locomotion. Locomotion produced by injections of PIC into the PLS was blocked by infusion of equal amounts of muscimol or GABA. Effective PLS injection sites were all confined to the trigeminal spinal nucleus or immediately ventral and medial to this in the adjacent lateral reticular formation. Trigeminal nerve peripheral field stimulation evoked locomotion after microinjection of PIC into the PLS, although this same facial stimulus was not effective prior to drug injection. We conclude that the MRF and PLS regions of the cat brain stem contain cells that produce locomotion when chemically stimulated, and we suggest that the PLS is closely related to or synonymous with the spinal nucleus of the trigeminal nerve. Furthermore, we suggest that stimulation of trigeminal afferents is analogous to stimulation of segmental afferent pathways in the production of locomotion (Sherrington, 1910; Jankowska et al., 1967; Afelt, 1970; Budakova, 1972; Grillner and Zangger, 1979).
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PMID:Locomotion produced in mesencephalic cats by injections of putative transmitter substances and antagonists into the medial reticular formation and the pontomedullary locomotor strip. 289 14

In the analysis of post-mortem brains of 14 chronic schizophrenic patients and 10 controls, biochemical evidence of a hyperdopaminergic state was found in the basal ganglia of schizophrenics; tyrosine hydroxylase activity was increased with a concomitant increase of homovanillic acid. Unusually high tyrosine hydroxylase activity was noted in 2 schizophrenic cases. The Bmax value of 3H-spiperone binding for schizophrenics was higher than the controls. We also found increased specific binding of 3H-kainic acid to the prefrontal cortex in schizophrenics. A negative correlation existed between 3H-kainic acid binding in the medial frontal cortex, and glutamic acid content in various brain areas. Increased immunoreactivity of substance P was found in more than ten brain areas. Methionine-enkephalin was also increased in three areas of the prefrontal cortex of schizophrenics. These results suggest that the hyperdopaminergic state co-existed with glutamatergic hypofunction and increased neuropeptides in various brain areas of chronic schizophrenic patients.
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PMID:Neurotransmitters, receptors and neuropeptides in post-mortem brains of chronic schizophrenic patients. 290 13

The effects of drugs on the K+-evoked release of met-enkephalin from superfused rat striatal slices were investigated using a specific radioimmunoassay. GABA, at concentrations of 50 microM and 100 microM, and the GABA agonist muscimol (50 microM), significantly inhibited the release. The inhibitory effect of GABA was reversed by picrotoxin suggesting that GABA inhibition is mediated by GABA receptors. Selected concentrations of the dopamine agonists apomorphine and ergonovine, as well as of haloperidol, acetylcholine, carbachol, noradrenaline, glutamic acid and substance P, had no effect on the release of metenkephalin. Increases in the evoked release (80%) and striatal enkephalin content (60%) were found in rats after chronic haloperidol administration, pointing to an increase in the synthesis and utilization of striatal enkephalin. No differences were found between the release from slices from morphine-tolerant/dependent and naive rats or after addition of naloxone to slices derived from tolerant/dependent animals. Selected concentrations of morphine and naloxone had no effect on release suggesting the absence of a mechanism for the regulation of enkephalin release involving autoreceptors.
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PMID:K+-evoked release of met-enkephalin from rat striatum in vitro: effect of putative neurotransmitters and morphine. 610 16

The possibility that L-glutamic acid (L-Glu) might be the neurotransmitter of baroreceptor afferents terminating in the nucleus tractus solitarius (NTS) and affecting activity of the autonomic nervous system was tested using a variety of techniques. Effects on blood pressure and heart rate of microinjections of L-Glu and antagonists into the NTS supported this contention. Use of blocking agents was confirmatory. Biochemical studies provided evidence that the agent (glutamic acid) is synthesized, stored and reaccumulated in these nerve endings. Furthermore, it was shown that L-Glu is released from the NTS in vivo. Degeneration of afferent terminals due to removal of the nodose ganglia reduced L-Glu levels in the NTS. After discussion of this and additional evidence that L-Glu is the transmitter and a consideration of reasons for eliminating other possibilities (substance P, etc.) it was concluded that L-glutamic acid is the neurotransmitter of baroreceptor afferents.
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PMID:Evidence that glutamic acid is the neurotransmitter of baroreceptor afferent terminating in the nucleus tractus solitarius (NTS). 611 75

Neurons of the lower brain stem maintain resting levels of arterial pressure (AP), mediate reflex responses from cardiopulmonary receptors, and are an important site of the hypotensive actions of alpha 2-adrenergic agonists. Details of the pathways and transmitters that mediate tonic and reflex control of AP are emerging. Afferent fibers of cardiopulmonary receptors in the ninth and tenth nerves terminate bilaterally in the nucleus of the tractus solitarius (NTS). Although some neurons contain substance P, the primary neurotransmitter appears to be the excitatory amino acid L-glutamate (L-glu). Neurons in rostral ventrolateral medulla, which most probably comprise the C1 group of epinephrine neurons, are also critical in AP control. C1 neurons project to innervate cholinergic preganglionic sympathetic neurons in the spinal cord. Stimulation of the C1 area electrically or with L-glu increases AP, while lesions or local injection of the inhibitory amino acid gamma-aminobutyric acid (GABA) lowers AP to levels comparable to spinal cord transection. Lesions of C1 neurons or their pathways abolish vasodepressor reflexes from baroreceptors and vagal afferents. In contrast, noradrenergic neurons of the caudal ventrolateral medulla, the A1 group, project rostrally to innervate, in part, vasopressin neurons of the hypothalamus. Stimulation of A1 neurons lowers AP, while lesions or GABA elevates it. We propose that C1 neurons comprise the so-called tonic vasomotor center of the brain stem and also mediate, via a projection from the NTS, the vasodepressor limb of baroreflexes. The NTS-C1 projection may be GABAergic.
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PMID:Brain stem catecholamine mechanisms in tonic and reflex control of blood pressure. 615 1

Rat substantia nigra slices were superfused with a physiological medium containing a diluted substance P (SP) antiserum, bacitracin and serum albumin to measure SP released in superfusates. As shown by measuring the degradation of a SP-labelled derivative incubated with cerebellar slices, this medium prevented the enzymatic inactivation of SP. Potassium (K+, 50 mM) and veratridine (5 X 10(-5) M) stimulated SP release and these effects were respectively prevented in absence of calcium and in presence of tetrodotoxin (5 X 10(-7) M). GABA (5 X 10(-5) M), nicotine (10(-6) M) and L-glutamic acid (5 X 10(-5) M) reduced the K+ (50 mM)-evoked release of SP. In contrast, glycine (5 X 10(-5) M), oxotremorine (5 X 10(-5) M), D-glutamic acid (5 X 10(-5) M) and serotonin (5 X 10(-5) M) were without effect. Pempidine (10(-5) M) prevented the inhibitory effect of nicotine (10(-6) M) on the K+-evoked release of SP. Glutamic acid diethyl ester (10(-4) M) completely abolished the L-glutamic acid-induced inhibition of the K+-evoked release of SP. Picrotoxin (5 X 10(-5) M) did not influence the L-glutamic acid inhibitory effect excluding the intervention of GABAergic mechanisms.
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PMID:Inhibitory effects of GABA, L-glutamic acid and nicotine on the potassium-evoked release of substance P in substantia nigra slices of the rat. 616 87

A solid phase enzyme-linked immunosorbent assay for quantitation of substance P is presented. The assay measures the capacity of soluble substance P to compete with the solid phase antigen for a limited quantity of specific substance P antibody. The solid-phase antigen consists of a synthetic substance P.poly-D-glutamic acid conjugate coated to polystyrene micro-ELISA plate wells. Soluble substance P and antibodies to substance P are first preincubated together and then added to the wells containing solid-phase antigen. Subsequently the wells are incubated with anti-antibodies conjugated to alkaline phosphatase. The wells are finally incubated with p-nitrophenyl phosphate an the absorbance is read in a spectrophotometer 16--24 hr after the start of the assay. The threshold for detection of substance P was 5--10 pg per well (0.25 ml). Substance P was extracted from rabbit eyes and the values obtained with the present method are compared with previously reported values based on radioimmunoassay.
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PMID:Enzyme-linked immunosorbent assay of substance P: a study in the eye. 617 96


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