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)

Intracerebroventricular injection of substance P (SP) enhanced the synthesis of dopamine and noradrenaline (measured as increase in DOPA formation after inhibition of the aromatic L-amino-acid decarboxylase) in rat brain. These biochemical effects were blocked in most brain regions by pretreatment with naloxone. SP also induced vasodilation, salivation and increased locomotor activity. These effects were not antagonized, but, in the case of locomotor activity, potentiated by naloxone. The data suggest the existence of specific SP-containing neuronal pathways for behavior, which pathways are not related to those regulating the synthesis of brain catecholamines.
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PMID:Opposite effects of naloxone on substance P-induced changes in brain DOPA synthesis and in locomotor activity in rats. 47 72

The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle or of a sham lesion on the neuropeptide content of the striatum and substantia nigra was investigated with or without 6 months L-3,4-dihydroxyphenylalanine (L-DOPA; 200 mg/kg per day) plus carbidopa (25 mg/kg per day) treatment. [Met5]- and [Leu5]enkephalin, substance P (SP), neurotensin (NT) and cholecystokinin (CCK) were measured by a combined HPLC/RIA method. Neurotensin levels were increased in the striatum, and [Leu5]enkephalin, and SP levels were reduced in the substantia nigra as a consequence of the lesion, while the levels of other peptides were unaltered. Administration of L-DOPA to sham-operated rats bilaterally increased SP levels in striatum and substantia nigra, and [Met5]enkephalin and CCK content in substantia nigra. L-DOPA treatment of 6-OHDA-lesioned rats increased [Met5]- and [Leu5]enkephalin and CCK levels in the striatum ipsilateral to the lesion but not on the intact side. In the substantia nigra, the lesion-induced decrease in [Leu5]enkephalin and SP was reversed by L-DOPA treatment, [Met5]enkephalin and CCK levels ipsilateral to the lesion were further enhanced, and there was an increase in NT ipsilateral to the lesion. Cryptic [Met5]- and [Leu5]enkephalin increased in the ipsilateral striatum following an 6-OHDA lesion. L-DOPA treatment did not alter cryptic enkephalin levels or the lesion-induced increase in cryptic [Met5]enkephalin, while cryptic [Leu5]enkephalin was further increased in lesioned animals given L-DOPA. These results suggest that the pattern of change in basal ganglia peptides in Parkinson's disease is not due solely to the destruction of the nigrostriatal pathway, the drug treatment of the disease or a combination of these factors.
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PMID:Effects of a unilateral 6-hydroxydopamine lesion and prolonged L-3,4-dihydroxyphenylalanine treatment on peptidergic systems in rat basal ganglia. 138 71

Previous studies have shown that L-dihydroxyphenylalanine (L-DOPA) administration to adult rats that had been subjected to dopamingergic denervation with 6-hydroxydopamine during early postnatal period, led to a marked decrease in the levels of striatonigral substance P (SP). The present study examined the hypothesis of whether there is a compensatory activation of SP biosynthesis in order to replenish the L-DOPA-induced SP depletion. Three-day old Sprague-Dawley rat pups were lesioned with 6-hydroxydopamine and were challenged with L-DOPA at about 60 days of age. The animals were sacrificed 75 min, 6 hr or 24 hr after the L-DOPA administration. The levels of SP (in the striatum and substantia nigra) were determined by radioimmunoassay. The abundance of SP-encoding preprotachykinin (PPT) messenger RNA (mRNA) in the striatum was determined by Northern blot analysis and the abundance of individual PPT-mRNAs (alpha, beta and gamma) was determined by nuclease protection assays. Concentrations of dopamine and its acid metabolite, dihydroxyphenyl acetic acid were determined by high-pressure liquid chromatography with electrochemical detection. At the 75 min time point, L-DOPA produced a greater decrease in SP levels in the striatum and the substantia nigra, than that observed with lesion alone. The SP levels recovered to lesioned-control levels by 6 hr and remained at this level at the 24-hr time point. This recovery was accompanied by a marked increase in striatal SP-encoding PPT-mRNA abundance at 6 hr; mRNA levels were below lesioned-control value at 24 hr. There were no differential changes in the individual SP-encoding PPT-mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Compensatory activation of substance P biosynthesis by L-dihydroxyphenylalanine in striatonigral neurons of neonatal dopaminergic denervated rats. 169 30

Cranial and spinal sensory ganglia of the guinea-pig were investigated by means of histochemistry and biochemistry for the presence of catecholamines and catecholamine-synthesizing enzymes. Sensory neurons exhibiting immunoreactivity to the rate-limiting enzyme of catecholamine synthesis, tyrosine hydroxylase (TH), were detected by immunohistochemistry in lumbo-sacral dorsal root ganglia, the nodose ganglion and the petrosal/jugular ganglion complex. The carotid body was identified as a target of TH-like-immunoreactive (TH-LI) neurons by the use of combined retrograde tracing and immunohistochemistry. Double-labelling immunofluorescence revealed that most TH-LI neurons also contained somatostatin-LI, but TH-LI did not coexist with either calcitonin gene-related peptide- or substance P-LI. TH-LI neurons did not react with antibodies to other enzymes involved in catecholamine synthesis, i.e., aromatic amino acid decarboxylase (AADC), dopamine-beta-hydroxylase (D beta H), and phenylethanolamine-N-methyl-transferase (PNMT). Petrosal neurons as well as their endings in the carotid body lacked dopamine- and L-DOPA-LI. Sensory neurons did not display glyoxylic acid-induced catecholamine fluorescence. Ganglia containing TH-LI neurons were kept in short-term organ culture after crushing their roots and the exiting nerve in order to enrich intra-axonal transmitter content at the ganglionic side of the crush. However, even under these conditions, catecholamine fluorescence was not detected in axons projecting peripherally or centrally from the ganglia. Sympathetic noradrenergic nerves entered the ganglia and terminated within them. Accordingly, biochemical analyses of guinea-pig sensory ganglia revealed noradrenaline but no dopamine. In conclusion, catecholamines within guinea-pig sensory ganglia are confined to sympathetic nerves, which fulfill presently unknown functions. The TH-LI neurons themselves, however, lack any additional sign of catecholamine synthesis, and the presence of enzymatically active TH within these neurons is questionable.
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PMID:Catecholamines and catecholamine-synthesizing enzymes in guinea-pig sensory ganglia. 197 3

Intravesical pressure recordings were performed in anaesthetized rats, and the effect of morphine on urinary bladder function was studied. The action of morphine was registered as its influence on bladder hyperactivity induced by central catecholaminergic stimulation with 1-dihydroxyphenylalanine (L-DOPA) after peripheral decarboxylase inhibition, and as its action on the response to regional injection of receptor agonists (acetylcholine (ACh), substance P (SP)) and peripheral motor nerve stimulation (PNS). The bladder response to L-DOPA was inhibited by intracerebroventricularly (i.c.v., fourth ventricle, 10 micrograms), as well as by systemically administered (1-5 mg kg-1 i.p.), morphine. Intravenous and i.c.v. naloxone antagonised the inhibitory actions of i.v. and i.c.v. morphine, respectively. Regional intra-arterial administration of morphine (0.01-5 mg) induced a weak bladder contraction per se, with a subsequent slight depression of bladder reactivity to ACh, SP and PNS. It is suggested that the inhibitory effect of morphine on bladder motility in the rat, is mainly mediated by central opioid-receptors. The direct peripheral effects on the detrusor muscle are weak, with an initial contraction followed by slight depression of the reactivity.
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PMID:Central and peripheral motor effects of morphine on the rat urinary bladder. 242 79

Tyrosine hydroxylase-like immunoreactive (TH-IR) neurons were observed from the embryonic day 17 (E17) to 6 weeks postnatally in two closely related nuclei of the limbic system, the bed nucleus of the stria terminalis (BNST) and the central nucleus of the amygdala (CNA) where they were restricted to circumscribed zones. These cells were scarce with an immature morphological aspect at E17. They progressively differentiated and increased in number until postnatal day 5 (P5), when their maximal density was reached. They were characterized as neurons by their ultrastructural appearance and the presence of both axo-somatic and axo-dendritic synaptic junctions. Moreover, TH-IR axons could be followed in the stria terminalis leaving the CNA, suggesting that part of TH-IR cells could be long projecting neurons rather than interneurons. A gradual decrease in the intensity of TH-IR and in density of labeled neurons was noted from P15 on, in both nuclei, (-50% at 4 weeks) until their total disappearance at 7 weeks. The significance of this TH-IR labeling regarding the catecholaminergic transmission remains unclear since these neurons did not contain the other catecholaminergic synthetic enzymes (DOPA-decarboxylase, dopamine-beta-hydroxylase, phenylethanolamine-N-methyl transferase) nor endogenous catecholamines. Double-labeling immunocytochemical methods, indicated that almost all the TH-IR neurons were colocalized with somatostatin 28 (SST) and with substance P (SP). Therefore these neurons expressed simultaneously 3 phenotypes, TH, SST and SP. This observation brings forth the notion of multiple neurotransmitter expression in transient neuronal populations and raises the question of neurotransmitter plasticity in the late postnatal development of the central nervous system (CNS). These neurons which were observed in two closely interconnected structures could be involved in early limbic circuits.
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PMID:Transient tyrosine hydroxylase-like immunoreactive neurons contain somatostatin and substance P in the developing amygdala and bed nucleus of the stria terminalis of the rat. 245 12

Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the primary pathology is thought to be a loss of dopaminergic neurons in the substantia nigra (SN). The mainstay of treatment has been the use of the drug L-DOPA, a drug that crosses the blood-brain barrier and is converted to dopamine. Recently, intracerebrally implanted grafts of adrenal tissue to promote functional recovery in nigral-damaged recipient animals and patients have been successfully performed. The recovery in these cases is said to be due to the dopamine present in the grafted adrenal tissue. This explanation has several fallacies, however. It is the contention of this paper that substance P is the active agent in the grafted tissue. This raises the possibility of improving the treatment for PD by the use of grafted tissue that is a purer source of SP or SP agonists.
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PMID:Adrenal grafting for Parkinson's disease: a role for substance P. 247 50

The present study examined the influences of dopamine (DA) receptor stimulation on enkephalin (Met5-enkephalin; ME) and tachykinin (substance P; SP) systems of basal ganglia of Sprague-Dawley rats, lesioned as neonates with 6-hydroxydopamine (6-OHDA). It has been proposed that the neonatal 6-OHDA-lesioned rat could serve as a model for the DA deficiency and self-injurious behavior (SIB) observed in the childhood neurological disorder. Lesch-Nyhan syndrome. In agreement with earlier work, the present study found that the neonatal 6-OHDA treatment at 3 days of age, reduced DA and caused an increase in ME and a decrease in SP content in the striatum and substantia nigra, when tested as adults. Administration of the DA precursor, L-dihydroxyphenylalanine (L-DOPA), to lesioned animals, induced SIB; increased DA and DOPAC levels; produced a greater decrease (-64%) in SP levels in the striatum and substantia nigra than was observed with lesion alone (-28%). The L-DOPA-induced decrease in SP levels and the SIB observed in the lesioned animals were blocked by pretreatment with the D1 receptor antagonist, SCH-23390. Moreover, administration of the D1 receptor agonist, SKF-38393, but not the D2 agonist, LY-171555, to lesioned animals mimicked the L-DOPA responses in all respects, except that the agonists did not alter DA or DOPAC levels. None of the DA agonists or antagonists treatments affected lesion-induced increase in ME levels in the striatum. These results indicate for the first time, that SIB precipitated by DA agonists in neonatal dopaminergic denervated animals, is associated with a marked and selective decrease in SP in the striatonigral SP neurons. This process has two components: (a) a retarded development of the SP system due to neonatal dopaminergic denervation: and (b) a depletion of the remaining SP, presumably by enhanced release due to D1 DA receptor-mediated activation of striatonigral SP neurons.
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PMID:D1 dopamine receptor-mediated substance P depletion in the striatonigral neurons of rats subjected to neonatal dopaminergic denervation: implications for self-injurious behavior. 248 60

The study of neurotransmitter receptors aids in the understanding of the normal anatomy, pharmacology, therapeutics and pathophysiology of disease processes involving the basal ganglia. Receptors may be studied in vitro by homogenate binding experiments, enzyme analysis or quantitative autoradiography and in vivo with positron emission tomography. In the substantia nigra (SN), receptors have been identified for somatostatin, neurotensin, substance P, glycine, benzodiazepine and GABA, opiates, dopamine, angiotensin converting enzyme (ACE) and serotonin. The striatum has receptors for dopamine, GABA and benzodiazepines, acetylcholine, opiates, substance P, glutamate and cholecystokinin. GABA and benzodiazepine receptors are also located in the globus pallidus. In Parkinson's disease, striatal dopamine D-2 receptors are elevated in patients that have not received L-DOPA therapy. This supersensitivity is reversed with agonist therapy. Muscarinic binding to cholinergic receptors seems to correlate with dopamine receptors. Delta opiate receptors are increased in the caudate and mu binding is reduced in the striatum. In the SN of patients with Parkinson's disease, there is reduced binding of somatostatin, neurotensin, mu and kappa opiates, benzodiazepine and GABA and glycine. In Huntington's disease, there is reduced binding of GABA and benzodiazepines, dopamine, acetylcholine, glutamate and CCK. There is increased binding of GABA in both the SN and globus pallidus. Glycine binding is increased in the substantia nigra and ACE is reduced.
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PMID:Receptors in the basal ganglia. 282 9

The changes in fluorescence intensity and number of visible catecholaminergic cells (CA-cells), as revealed by means of a histofluorescence technique, were used as indicators of the effects of various pharmacological agents upon CA-cells in the retina of fishes (Cyprinus carpio and Eugerres plumieri). The study includes in vivo and in vitro experiments. In the in vivo experiments, intravitreal injection, two or three hours before eye enucleation, of 10 microgram L-DOPA, dopamine, or noradrenaline accentuated CA-cell fluorescence and increased the number of visible cells, whereas 10 microgram of tyramine, octopamine, synephrine, or adrenaline reduced the endogenous fluorescence. Intramuscular injection of reserpine (3 mg/kg) abolished CA-cell fluorescence. In the in vitro experiments, pieces of isolated retinas were incubated for three or 30 minutes in media containing different drugs. Only minor changes in fluorescence were detected after three minutes of incubation, but after 30 minutes, dopamine (20 microM) markedly enhanced CA-cell fluorescence. Carbachol (20 mM), acetylcholine (10 mM) plus BW-anticholinesterase (1 mM) or substance P(1.6 x 10(-2) mM), all reduced CA-cell fluorescence. Kainic acid (20 mM) abolished fluorescence from CA-cell somata, while fluorescent fiber networks remain unchanged. L-aspartate (5 mM) and GABA (10 mM) in the incubation medium did not influence fluorescence intensity. The results are relevant to, and consistent with, electrophysiological observations of dopamine-mediated spatial effects on horizontal cell potentials.
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PMID:Drug-induced changes in catecholaminergic cells of the fish retina. 616 65


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