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)

We investigated effects of calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A (NKA) on pial arterioles in newborn pigs. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. Initial diameters were approximately 100 microns. Calcitonin-gene related peptide dilated pial arterioles by 22 +/- 8% at 10(-9)M and by 34 +/- 6% at 10(-8)M (n = 8), and this response was not significantly altered by prior administration of indomethacin (5mg/kg, iv) (n = 6) or administration of NG-methyl-L-arginine (5mg/kg, iv, and 10(-3)M in CSF) (n = 10). Substance P dilated arterioles at 10(-10)M through 10(-5)M (maximal response = 23 +/- 3%) (n = 6), and this response was unaffected by indomethacin administration (n = 6). In contrast, NG-methyl-L-arginine blocked much of the pial arteriolar dilation to SP. Unlike the other two peptides, NKA did not change pial arteriolar diameter. Radioimmunoassay determinations indicated that cerebrospinal fluid levels of 6-keto-prostaglandin F1 and prostaglandin E2 did not change appreciably during application of CGRP or SP. We conclude that CGRP and SP but not NKA are dilator stimuli in the piglet pial circulation. Dilation by CGRP probably involves direct activation of receptors on vascular smooth muscle, while SP probably partially dilates pial arterioles via release of an endothelium-dependent relaxing factor.
 ...
PMID:Effects of trigeminal neurotransmitters on piglet pial arterioles. 128 73

In halothane-anesthetized and -ventilated cynomologus macaque monkeys, the effects of administering vehicle (n = 3) or the neutral endopeptidase inhibitor N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine (16 mg/kg, n = 5; or 100 mg/kg, n = 3, intravenously) was examined. Cisternal CSF aliquots were examined by radioimmunoassay: 1) for Met enkephalin; 2) after trypsin and carboxypeptidase B treatment for encrypted enkephalin (X-ENK); 3) for substance P; and 4) for unmetabolized drug. Similar measures were carried out in femoral artery and femoral venous plasma, except that substance P was not assayed. In CSF, prior to drug, low, but measurable levels of enkephalin (61 pg/ml), X-ENK (285 pg/ml) and substance P (16 pg/ml) were observed. Vehicle-injected animals showed no change from baseline levels over a 4-hr sampling period in either plasma or CSF levels. In contrast, following 16 mg/kg, in CSF, there was a significant 9-fold increase in MET and 11-fold increase in X-ENK at 30 min. CSF-substance P levels rose also by a factor of 2, with the peak effect observed at 60 min. All levels displayed a significant reduction by 4 hr. There was no statistical difference between the maximum effects observed with either the 16- or 100-mg/kg dose. Plasma peptide levels of enkephalin and X-ENK were not altered by drug. CSF displayed significant drug levels by 30 min, which were between 0.1 and 1% of levels observed concurrently in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of [N-(L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine (SCH32615), a neutral endopeptidase (enkephalinase) inhibitor, on levels of enkephalin, encrypted enkephalins and substance P in cerebrospinal fluid and plasma of primates. 170 28

Seventy patients aged from one month to 18 years with seizure disorders were classified into three groups: I. Patients who had hard control seizure attacks even under medication; II. those who had occasional seizure attacks (less than 6 times per year) and III. those who had no seizure attacks after receiving medication for at least one year. Blood samples were taken for somatostatin, substance P, prolactin and vasoactive intestinal peptide (VIP) assays. Lumbar puncture was made in 32 children and CSF samples were also assayed for neuropeptides. Somatostatin levels in serum were significantly elevated in group I and group II (P = 0.05, ANOVA) but not in group III and control group. Similar observations were made in substance P, prolactin and VIP studies. In CSF, the somatostation can better indicate the difference between epileptic and normal children (comparison with group I, P greater than 0.001; with group II, P less than 0.001; even with those who were seizure free after medication, P less than 0.05). In conclusion, the levels of several neuropeptides (somatostatin, substance P. prolactin, VIP) were elevated in children with seizure disorders both in serum and CSF. The present investigation provides a new category for the understanding of the pathogenesis, treatment as well as prognosis of seizure disorders.
 ...
PMID:Somatostatin, substance P, prolactin and vasoactive intestinal peptide levels in serum and cerebrospinal fluid of children with seizure disorders. 171 68

Three different molecular forms of angiotensin converting enzyme (ACE) (approximately Mr 150,000, 80,000 and 40,000, respectively), have been recovered from human cerebrospinal fluid. All three enzymes were inhibited by captopril and enalapril and their activity was potentiated by chloride ions. They were capable of degrading Leu-enkephalin-Arg6 and substance -P, but gave no conversion of neurokinin A. In all these aspects, the CSF enzymes were identical with the human pulmonary enzyme. The Mr 40,000 form of ACE is the smallest active form of the enzyme hitherto reported and is likely to represent a fragment of the C-terminal part of native ACE, where its active center is located.
 ...
PMID:Molecular heterogeneity of angiotensin converting enzyme in human cerebrospinal fluid. 171 7

CSF substance P immunoreactivity was determined in a group of inpatient controls and acutely manic, euthymic, or depressed unmedicated unipolar and bipolar subjects; a second outpatient group of euthymic bipolar patients (on and off lithium) and normal volunteers was also studied. No group differences and no lithium effects were detected. CSF that was allowed to stand at room temperature for brief periods and then was refrozen contained elevated levels of the immunoreactive substance P, an observation that may account for a previous report of elevated CSF substance P immunoreactivity in psychiatric disorders.
 ...
PMID:CSF substance P immunoreactivity in affective disorders. 241 4

Eighteen patients with chronic pain syndromes of organic origin were treated by means of high frequency transcutaneous nerve stimulation (hi-TNS). The CSF levels of receptorassayable Fraction I and II endorphins, substance P-like immunoreactivity (SPLI), and the monoamine metabolites 5-HIAA, HVA and MOPEG were measured before and after one week of daily treatment. Furthermore, the effects on experimental pain measures were determined. The therapeutic effect was evaluated after 30 days and 3 months of treatment. Patients with low initial concentrations of endorphins in CSF, lower than those observed in healthy volunteers, tended to have the best response to hi-TNS. There were significant increases in Fraction I endorphins and SPLI in CSF, most pronounced in the patients who responded. There were no significant changes in 5-HIAA, HVA or MOPEG in CSF. However, in early responders, the serotonin metabolite 5-HIAA tended to decrease as contrasted to an increase in non-responders. The difference between the groups was statistically significant. Confirming our earlier studies, the therapy induced changes in pain measures showed a significant, positive correlation with increasing Fraction I endorphins in CSF. Our results suggest that hi-TNS induces central changes in the endorphinergic, serotonergic and possibly substance-P-ergic systems.
 ...
PMID:Long-term high frequency transcutaneous electrical nerve stimulation (hi-TNS) in chronic pain. Clinical response and effects on CSF-endorphins, monoamine metabolites, substance P-like immunoreactivity (SPLI) and pain measures. 241 23

Calcitonin gene-related peptide (CGRP) was found to potently inhibit a substance P endopeptidase isolated from human CSF. CGRP potentiated substance P irritant actions; a possible mechanism is interaction for a common metabolic step. Somatostatin is another peptide capable of competing with substance P endopeptidase.
 ...
PMID:Calcitonin gene-related peptide is a potent inhibitor of substance P degradation. 241 71

Of two related Macaca species, the rhesus (M. mulatta), acquires opiate tolerance and dependence more readily than the cynomolgus (M. fascicularis). In the cynomolgus, mu-opiate receptors were significantly fewer in the caudate nucleus and globus pallidus; delta-sites were fewer in the thalamus. kappa-Sites showed no species difference. The levels of [Met5]enkephalin, substance P and dynorphin B in various brain areas were comparable. On the other hand, receptor-assayed endorphin activity was higher in CSF of cynomolgus than rhesus monkeys.
 ...
PMID:Opiate receptors, neuropeptides in CNS and CSF of two Macaca species with different responsiveness to opiates. 242 Jun 16

Improved knowledge about biochemical mechanisms underlying pain suppression by CNS electric stimulation is one condition for the further advancement of this form of treatment. In 6 patients treated with PVG stimulation and in 14 with spinal cord stimulation the concentration of substance P-like immunoreactivity in lumbar CSF increased significantly following stimulation. However, these changes may be unspecific and not directly related to the suppression of pain. Measurements of somatostatin, cholecystokinin, vasoactive intestinal polypeptide, neurotensin and monoamine metabolites in CSF showed no changes related to stimulation and the ensuing pain relief. Possible reasons for these negative findings are discussed.
 ...
PMID:Possible neurohumoral mechanisms in CNS stimulation for pain suppression. 242 25

In vivo release of substance P (SP) was measured by microdialysis in the nucleus tractus solitarii (nTS) in adult cats. Small perfused semipermeable tubules (microdialysis probes) were implanted stereotaxically in the nTS, at the position of respiration-related neurons and perfused with artificial CSF. SP was determined by radioimmunoassay of the perfusate. Increased extracellular concentrations of SP-like immunoreactivity (SP-LI) were measured during hypoxia induced in artificially ventilated cats. In addition, a prolonged increase in the extracellular SP-LI concentration was encountered after cervical vagotomy. The results corroborate the suggestion that SP is a mediator of the central response to hypoxia.
 ...
PMID:In vivo release of substance P in the nucleus tractus solitarii increases during hypoxia. 242 79


1 2 3 4 5 6 7 8 Next >>