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)

This study examined whether a relationship exists between the degree of dopamine (DA) loss and the changes in opioid (Met5-enkephalin, ME; dynorphin A (1-8) (DYN)) or tachykinin (substance P, SP) peptidergic systems in basal ganglia (caudate and putamen) and limbic (frontal cortex) regions of postmortem tissue samples derived from patients who died of Parkinson's disease (PD). The levels of ME, SP and DYN were determined by radioimmunoassays. The levels of DA and 5-hydroxytryptamine (5-HT) and their metabolites were determined by HPLC with electrochemical detection. The degree of loss of DA in PD tissues was classified into two major categories, those with less than 80% and those with more than 80% loss as compared to control. The results reveals that only the category with greater than 80% DA loss exhibited lower levels of ME in caudate and SP in putamen whereas no differences were observed in the levels of DYN in these regions. The frontal cortical region exhibited no changes in the levels of peptides. In other studies, experimental DA deficiency in rodents induced by neurotoxin such as 6-hydroxydopamine (6-OHDA) produced an increase in ME and a decrease in SP in basal ganglia. However, the levels of both peptides were lower in postmortem Parkinsonian basal ganglia in the present study. It appears that there is a DA-dependent, secondary loss of enkephalin and tachykinin peptides in PD. In view of the involvement of these peptidergic systems in the regulation of behaviour, movement, memory and other functions, derangements in these systems should be considered as additional factors in the progression of symptoms of PD.
 ...
PMID:Dopamine dependent decrease in enkephalin and substance P levels in basal ganglia regions of postmortem parkinsonian brains. 171 Nov 65

Rats chronically implanted with intrathecal catheters received intrathecal injections (10 microliters followed by 10 microliters saline flush) of either saline (n = 5), somatostatin (100 micrograms, n = 10), the somatostatin analog BIM 23003 (100 micrograms, n = 5), the somatostatin analog SMS 201-995 (100 micrograms, n = 5), the substance P analog [D-Pro2, D-Trp7,9] SP (10 micrograms, n = 10), or dynorphin A (1-17) (20 nmol, n = 8). These doses (somatostatin, substance P and dynorphin A) were selected based on previous studies in which they caused significant motor deficits. Effects on thermal cutaneous nociception, behavior, motor function and spinal cord histopathology were evaluated. All peptides caused severe neurotoxicity, evidenced by flaccid hind leg paralysis and lumbar spinal neuronal degeneration, which was accompanied by an inflammatory reaction in meninges and spinal gray matter. Histopathological changes had developed within 24 h after injection of somatostatin, substance P analog and dynorphin A, showing mild to severe neuronal degeneration and mild inflammatory responses in spinal cord and meninges. Significant antinociceptive effects, due to severe neurotoxic effects, were only observed following intrathecal injection of SMS 201-995 and the substance P analog. Potential neurotoxic mechanisms of the different peptides are discussed.
 ...
PMID:Intrathecal somatostatin, somatostatin analogs, substance P analog and dynorphin A cause comparable neurotoxicity in rats. 171 Nov 72

To determine if substance P- or prodynorphin-containing neurons of the medial nucleus of the amygdala and medial bed nucleus of the stria terminalis send projections to the medial preoptic area in the male Syrian hamster, we placed a fluorescent retrograde tract tracer (either Fluoro-gold, or rhodamine- or fluorescein-impregnated latex microspheres) into the medial preoptic area. Five to seven days later, the animals were treated with colchicine, allowed to survive for 48 h and the brains were processed for immunofluorescence histochemistry. Tissue sections were incubated in either rat anti-substance P or rabbit anti-C-peptide (the C-terminal sequence of dynorphin B) antiserum followed by incubation in either fluorescein- or rhodamine-conjugated anti-rabbit or anti-rat antiserum. When the injection site of retrograde tracer was centered within the caudal one-third of the medial preoptic area, labeled cell bodies were observed caudally in the medial part of the bed nucleus of the stria terminalis. Retrogradely labeled cell bodies were also observed in the posterodorsal subdivision of the medial nucleus of the amygdala. Both prodynorphin and substance P immunolabeling were observed in retrogradely labeled neurons in these two areas but fewer of these projection neurons were immunolabeled with substance P antiserum than with C-peptide antiserum. These projections may play a role in the peptidergic modulation of reproductive behavior in this species.
 ...
PMID:Prodynorphin- and substance P-containing neurons project to the medial preoptic area in the male Syrian hamster brain. 171 17

The effects of striatal dopamine denervation and levodopa replacement therapy on neuronal populations in the rat striatum were assessed by measurement of glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) activities in the striatum, dynorphin and substance P concentrations in the substantia nigra, and enkephalin concentration in the globus pallidus. Rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway were treated for 21 days with levodopa (100 mg/kg/day, i.p., with 25 mg/kg benserazide) on either an intermittent (b.i.d.) or continuous (osmotic pump infusion) regimen and sacrificed following a three day drug washout. In saline-treated control rats, striatal GAD activity and globus pallidus enkephalin content were elevated and nigral substance P content was reduced ipsilateral to the 6-OHDA lesion. Intermittent levodopa treatment further increased GAD activity, decreased CAT activity, restored substance P to control levels, markedly increased dynorphin content, and had no effect on enkephalin. In contrast, continuous levodopa elevated globus pallidus enkephalin beyond the levels occurring with denervation, but had no effect on any of the other neurochemical measures. These results indicate that striatal neuronal populations are differentially affected by chronic levodopa therapy and by the continuous or intermittent nature of the treatment regimen. With the exception of substance P, levodopa did not reverse the effects of the 6-OHDA lesion but, rather, either exacerbated the lesion-induced changes (e.g. GAD and enkephalin) or altered neurochemical markers which had been unaffected by the lesion (e.g. CAT and dynorphin).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Levodopa replacement therapy alters enzyme activities in striatum and neuropeptide content in striatal output regions of 6-hydroxydopamine lesioned rats. 171 9

There was no apparent difference in the regional distribution of neuropeptides in the brain of male and female rats. The highest levels of immunoreactive leu-enkephalin, TRH, substance P and somatostatin were found in the hypothalamus, while the striatum and the cerebral cortex had the highest concentrations of met-enkephalin and cholecystokinin respectively. The lowest concentrations of these were found in the cerebellum. Enkephalins (cerebral cortex), substance P (cerebral cortex and brain stem), and somatostatin (brain stem and striatum) showed higher level in the female while enkephalin and substance P contents in the anterior pituitary were higher in the male.
 ...
PMID:The regional distribution of thyrotropin releasing hormone, leu-enkephalin, met-enkephalin, substance P, somatostatin and cholecystokinin in the rat brain and pituitary. 171 78

Different regions of the prostate gland, namely prostatic capsule, peripheral prostate and central prostate (subdivided into proximal (near the bladder neck), distal (near the verumontanum) and midway between these areas) were obtained from 32 obstructed (stable obstructed, n = 8; unstable obstructed, n = 13; acute retention, n = 11) and five control patients. The innervation of these tissues was studied both histochemically to localise acetylcholinesterase activity and immunohistochemically for dopamine-beta-hydroxylase, 5-hydroxytryptamine, vasoactive intestinal polypeptide, neuropeptide Y, leu- and met-enkephalin, calcitonin gene-related peptide, substance P and somatostatin. In control patients the greatest density of nerves was found in the proximal central prostate, followed by the anterior capsule and distal central prostate, with the least density in the peripheral prostate. The greatest density of nerves were acetylcholinesterase positive and immunoreactive to neuropeptide Y followed (in decreasing order) by nerves immunoreactive to: vasoactive intestinal polypeptide and dopamine beta-hydroxylase; leu-enkephalin and 5-hydroxytryptamine; calcitonin gene-related peptide; met-enkephalin; substance P; somatostatin. In addition a group of periacinar 5-hydroxytryptamine-immunoreactive cells and ganglia containing acetylcholinesterase, dopamine beta-hydroxylase and all of the peptides studied except somatostatin were identified. In the prostate gland from obstructed patients there was a significant reduction in the density of acetylcholinesterase-positive nerves (p less than 0.001) when compared with the controls. A similar trend was found for dopamine beta-hydroxylase, 5-hydroxytryptamine and all of the putative neuropeptides in most areas of the prostate, the most notable exceptions being in the peripheral prostate, with an increase in dopamine beta-hydroxylase- and leu-enkephalin-immunoreactive nerves in all three groups of obstructed patients an an increase in vasoactive intestinal polypeptide- and calcitonin gene-related peptide-immunoreactive nerves in those presenting in urinary retention. The functional significance of these findings is discussed.
 ...
PMID:The innervation of the human prostate gland--the changes associated with benign enlargement. 171 53

A biochemical model of chronic trigeminal facial pain with elevated substance P (SP) and co-dysfunctional dopamine (DA), norepinephrine (NE) and purinergic systems is proposed. The serotonergic system is hypoactive as judged by low 5 hydroxyindoleacetic acid (5HIM). In distinction, intracerebral opioids may not be dysfunctional in facial pain as measured by normal levels of beta endorphin (BE). The neuropeptides somatostatin (SOM), cholecystokinin (CCK), met and leu-enkephalin (MENK, LENK) have very small picogram concentrations in these pain patients, but no definite conclusion can be reached on their role in trigeminal pain, alone or with monoamines, because of the small numbers, both sample size and concentrations. Interpretive obstacles to such human neurochemical studies suggest that future work might move to human clinical trials comodulating SP down, inhibitory peptides (SOM, CCK) up, and enhancing monoamine systems.
 ...
PMID:Trigeminal facial pain: a model of peptides and monoamines in intracerebral cerebrospinal fluid. 172 75

Chemical derivatization by phenylglyoxal (PGX) was applied to the identification of arginine in the neuropeptides dynorphin A (1-6) and substance P. The obtained products were separated on a short reversed phase C18 column and analysed on-line with the photodiode array UV technique. The selective attachment of a chromogenic molecule into the arginine residue resulted in significant change in the absorbance spectra around 250 nm, depending on the number of PGX molecules attracted. Further analysis employed fast atom bombardment mass spectrometry (FAB MS) and C-terminal sequencing for detailed verification of the derivatives formed during modification with PGX. The results clearly demonstrated that the photodiode array technique, when combined with chemical modification of certain amino acids, provides new possibilities for the analysis of peptide structures.
 ...
PMID:Application of photodiode array detection and fast atom bombardment mass spectrometry for the identification of the arginine residue in neuropeptides. 172 24

The responses of extrapyramidal and limbic neuropeptide and striatal dopamine and serotonin systems were evaluated after treatment with fenfluramine in rats. After multiple administrations of fenfluramine, its active metabolite, norfenfluramine, and methamphetamine (METH), striatal neurotensin (NT) content was similarly increased to approximately 200% of control. In contrast, nigral NT levels were unaltered by fenfluramine, intermediately increased by norfenfluramine (148% of control) and maximally increased by METH (267% of control). Striatal and nigral substance P (SP) and dynorphin A (Dyn) systems were unaltered by fenfluramine, whereas norfenfluramine caused an intermediate increase in striatal Dyn content but did not significantly alter striatal SP or nigral SP and Dyn levels. However, METH significantly elevated striatal and nigral Dyn and SP concentrations to 280 to 425% (Dyn) and 140% (SP) of control. For the most part, the response of the limbic peptides was similar to that seen in the striatum with a couple of notable differences. Further investigation of the striatal NT system showed that the increases induced by fenfluramine were completely blocked by the D1 antagonist, SCH 23390, and the noncompetitive N-methyl-D-aspartate antagonist, MK801. Depletion of 5-hydroxytryptamine with pretreatment by parachloroamphetamine did not alter the response of the striatal NT system to fenfluramine. The present results demonstrate common and unique features in the response of peptide systems to fenfluramine and methamphetamine, which might explain some of the similarities and differences between these two drugs.
 ...
PMID:Response of extrapyramidal and limbic neuropeptides to fenfluramine administration: comparison with methamphetamine. 172 53

A reverse-phase, high-performance liquid chromatographic (HPLC) method was employed to separate and characterise five neuropeptides from complex mixtures, with important advantages over methods employed earlier using combined HPLC-RIA studies. Peptides were separated using 0.5M pyridine-0.5M formic acid buffer, pH 4, containing propan-l-ol 14% (met-enkephalin, leu-enkephalin, neurotensin) or 20% (CCK-8-S, substance P) at a flow rate of 1.0 ml/min. Isocratic conditions, and volatile solvents, resulted in a highly reproducible method, producing samples in a form designed for subsequent RIA. The application and importance of the procedure is demonstrated by comparison of the measurements of apparent peptide levels in crude brain extracts with those of authentic peptides as determined after HPLC purification.
 ...
PMID:Isocratic reverse-phase HPLC separation and RIA used in the analysis of neuropeptides in brain tissue. 172 86


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