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)

The immediate-early gene c-fos has been proposed to play a role in induction of neurotensin/neuromedin N (NT/N) gene expression in the striatum following acute haloperidol (HAL) treatment. We utilized mice with targeted disruption of the c-fos gene to directly test this hypothesis. A robust increase in NT/N gene expression was observed in the dorsolateral striatum (DLSt) in both wild-type (WT) and c-fos-deficient mice 4-6 h after a single injection of HAL (1 or 4 mg/kg) indicating that products of the c-fos gene are not absolutely required for induction of NT/N mRNA. The basal expression of preprotachykinin, preproenkephalin and preprocholecystokinin mRNAs did not differ between WT and c-fos knockout mice. HAL treatment first increased striatal NT/N mRNA on postnatal day (PD) 10. HAL-induced NT/N mRNA levels were significantly lower in c-fos knockout mice than in WT mice on PD 10 and 15. These findings indicate that reliance on c-fos may be greater earlier in development and that redundant molecular pathways can lead to induction of NT/N mRNA in mouse striatum.
 ...
PMID:Haloperidol regulates neurotensin gene expression in striatum of c-fos-deficient mice. 922 26

The aim of the present study was to further characterize the involvement of the mesolimbic dopamine system in central blood pressure regulation, with particular emphasis on the interaction of this system with the effects of circulating vasopressin. In conscious rats we stimulated the release of endogenous dopamine from mesolimbic/mesocortical terminals by administration of the substance P analogue DiMe-C7 ([pGlu5, MePhe8, Sar9]-Substance P5-11; 10 nmol) into the ventral tegmental area. Chemical stimulation of the ventral tegmental area resulted in a significant increase in blood pressure and heart rate. These effects were prevented by either bilateral electrolytic lesions of the hypothalamic supraoptic nucleus or by systemic pretreatment with the dopamine D2 receptor antagonist raclopride (0.5 mg/kg). Stimulation of the ventral tegmental area also produced a marked increase in the expression of the proto-oncogene c-fos in the supraoptic nucleus and a significant increase in plasma vasopressin levels, suggesting activation of vasopressinergic neurons in this nucleus. However, this effect of stimulation of the ventral tegmental area was not significantly inhibited by pretreatment with raclopride. We suggest that the effects on blood pressure and heart rate of stimulation of the ventral midbrain by micro-injection of DiMe-C7 are the result of combined activation of both dopaminergic and non-dopaminergic cell bodies in this region. Stimulation of non-dopaminergic cells in the ventral midbrain may induce a moderate increase in plasma vasopressin levels by activation of the supraoptic nucleus. An additional stimulation of dopaminergic cells in the ventral midbrain allows the increase in circulating vasopressin levels to become manifest as a pressor response, possibly by inhibition of vasopressin-induced facilitation of baroreflex responses.
 ...
PMID:A functional interaction between the mesolimbic dopamine system and vasopressin release in the regulation of blood pressure in conscious rats. 930 Apr 2

Striatal c-fos induction was blocked by local administration of phosphorothioated c-fos antisense oligonucleotides (AS-ODN) to examine the possible role of caffeine-induced c-fos expression in transcriptional regulation of striatal preproenkephalin, prodynorphin, preprotachykinin A and neurotensin/neuromedin N. Caffeine (100 mg/kg i.p.) induced both c-fos mRNA and Fos-protein, and this induction was significantly attenuated by intrastriatal injection of 4 (but not 1) nmol c-fos AS-ODN. This suggests that, in addition to translational arrest, other mechanisms may be involved in the mediation of antisense action. The action of the AS-ODN was sequence specific. The antisense blockade of c-fos reduced the effect of caffeine on the expression of mRNAs for preprotachykinin A and neurotensin/neuromedin N in the ventrolateral caudate-putamen. Levels of preproenkephalin and prodynorphin transcripts were unaffected. Thus caffeine induction of striatal preprotachykinin A mRNA and neurotensin/neuromedin N mRNA, but not of preproenkephalin mRNA or prodynorphin mRNA, may at least in part be mediated by a pathway involving Fos protein. The findings illustrate the utility of blockade of gene expression with antisense oligonucleotides for in vivo studies of drug actions.
 ...
PMID:Involvement of a c-fos-dependent mechanism in caffeine-induced expression of the preprotachykinin A and neurotensin/neuromedin N genes in rat striatum. 942 Nov 73

We have used a partial sciatic nerve ligation model to examine the time course for changes in the expression of mRNA for three peptides related to pain transmission at spinal sites (dynorphin, enkephalin and substance P), during the development of allodynia. Enhanced expression of mRNA for dynorphin and substance P was observed in the dorsal horn on the same side as the partial nerve ligation. Increased expression of dynorphin mRNA was biphasic. The initial increases in expression of dynorphin mRNA occurred at 3 h, and a secondary peak was observed 1-3 days after surgery. The secondary increases coincided roughly with increased substance P mRNA expression. However, both dynorphin and substance P mRNA returned to control values after 1 week despite continuing allodynia. No significant changes in expression of mRNA for enkephalin were observed. The elevation of substance P mRNA in intrinsic spinal cord neurons may be secondary to changes in immediate early genes c-fos and jun-B, whereas the expression of dynorphin and enkephalin mRNA is differently regulated. The results also suggest that changes in the expression of the three neuropeptides are not critically involved in the development and maintenance of chronic pain or allodynia.
 ...
PMID:Temporal changes in spinal cord expression of mRNA for substance P, dynorphin and enkephalin in a model of chronic pain. 942 59

Stimulation of the cornea activates neurons in two distinct regions of the spinal trigeminal nucleus: at the transition between trigeminal subnucleus interpolaris and subnucleus caudalis and at the transition between trigeminal subnucleus caudalis and the upper cervical spinal cord as estimated by expression of the immediate early gene, c-fos. To determine if receptors for substance P or neurokinin A, neurokinin 1 and neurokinin 2 receptors, respectively, contribute to the production of Fos-positive neurons in these brainstem regions, receptor-selective antagonists were given intracerebroventricularly 15 min prior to stimulation of the cornea in anesthetized rats. The number of Fos-positive neurons produced in superficial laminae at the trigeminal subnucleus caudalis/cervical cord transition by application of the selective small fiber excitant, mustard oil, to the corneal surface was reduced by the neurokinin 1 receptor antagonist, CP99,994 (5-100 nmol, i.c.v.) and the neurokinin 2 receptor antagonist, MEN10,376 (0.01-1.0 nmol, i.c.v.). Combined pretreatment with CP99,994 and the competitive N-methyl-D-aspartate receptor antagonist, CPP, caused a greater reduction in c-fos expression at the subnucleus caudalis/cervical cord transition than after either drug alone suggesting interaction between receptors for glutamate and substance P. Tachykinin receptor antagonists did not reduce the number of Fos-positive neurons produced at the subnucleus interpolaris/subnucleus caudalis transition. The elevation in plasma concentration of adrenocorticotropin, but not the increases in arterial pressure or heart rate, evoked by corneal stimulation was prevented by pretreatment with CP99,994 or MEN10,376 at doses lower than those needed to reduce c-fos expression. The results indicate that receptors for substance P and neurokinin A contribute to the transmission of sensory input from corneal nociceptors to brainstem neurons in trigeminal subnucleus caudalis and to increased activity of the hypothalamo-pituitary axis that accompanies acute stimulation of the cornea.
 ...
PMID:Selective blockade of substance P or neurokinin A receptors reduces the expression of c-fos in trigeminal subnucleus caudalis after corneal stimulation in the rat. 946 Jul 60

Using in situ hybridization, we examined the mRNA expression for several immediate early genes in dopamine-innervated brain areas following electrical burst vs. regular stimulation of the medial forebrain bundle in anaesthetized rats. Two hours after 5 Hz burst stimulation, the expression of the nerve growth factor-inducible clone A (NGFI-A) mRNA was increased in the medial part of the striatum. This increase was prevented by pretreatment with the dopamine-D1 receptor antagonist, SCH23390 (0.1 mg/kg i.p.). After 8 Hz burst stimulation, NGFI-A mRNA expression was increased in the medial, central and lateral parts of the striatum. Induction occurred predominantly in cells expressing mRNAs for the dopamine-D1 receptor, substance P and dopamine and cAMP-regulated phosphoprotein (DARP-32). Regular stimulation had no effect on NGFI-A mRNA expression. The induction of NGFI-A was related to the levels of dopamine released by burst or regular stimulation as demonstrated with in vivo amperometry. Two hours after stimulation, the expression of none of the other genes studied was altered. One hour after 8 Hz burst stimulation, the expression of NGFI-A, NGFI-B and jun-B mRNAs was increased in the striatum and that of NGFI-A, NGFI-B, c-fos, fos-B and jun-B mRNAs was variably increased in the nucleus accumbens and lateral septum. These results provide additional support for the physiological importance of burst firing activity in midbrain dopamine neurons for the activation of their target cells. They demonstrate a spatial and temporal specificity as regards the brain region, the gene activated, the receptor involved and the phenotype of the cells affected.
 ...
PMID:Increased expression of NGFI-A mRNA in the rat striatum following burst stimulation of the medial forebrain bundle. 946 31

The src homology 2 (SH2) domain-containing protein-tyrosine phosphatase SHP-2 has been implicated as an important positive regulator of several mitogenic signaling pathways. SHP-2 has more recently been shown to be tyrosine phosphorylated and recruited to the gp130 component of the ciliary neurotrophic factor (CNTF) receptor complex upon stimulation with CNTF. CNTF does not, however, have a proliferative effect on responsive cells, but rather enhances the survival and differentiation of sympathetic, motor, and sensory neurons. In this study, expression of an interfering mutant of SHP-2 in the neuroblastoma cell line NBFL increased CNTF induction of a vasoactive intestinal peptide (VIP) reporter gene, and in cultures of sympathetic neurons, it resulted in an up-regulation of endogenous VIP and substance P (SP) gene expression. Members of the CNTF family of cytokines transmit their signal by activating signaling pathways involving both STAT and Fos-Jun transcription factors. In CNTF-stimulated NBFL cells that constitutively express the SHP-2 interfering mutant, there was increased and prolonged formation of STAT/DNA complexes, but decreased AP-1 binding activity, that mirrored a down-regulation of c-fos expression both at the mRNA and protein level. Taken together, these data indicate that SHP-2 has dual and opposing roles in a signaling cascade triggered by the same ligand, as illustrated by its ability to differentially regulate the levels of activity of both STAT and AP-1 transcription factors.
 ...
PMID:Coordinate regulation of STAT signaling and c-fos expression by the tyrosine phosphatase SHP-2. 949 48

The D3 dopamine receptor, a D2-like receptor, is selectively expressed in the ventral striatum, particularly in the shell of nucleus accumbens and islands of Calleja, where it is found in medium sized substance P neurons. The latter co-express the D1 receptor whose interaction with the D3 receptor was studied by treating rats with selective agonists and antagonists. In agreement with the opposite cAMP response, they mediate in cultured neuroblastoma cells, the D1 and D3 receptors exerted opposite influences on c-fos expression in islands of Calleja. However, in agreement with the synergistic influence of cAMP on D3 receptor-mediated mitogenesis on the same cultured cells, D1 and D3 receptor stimulation in vivo synergistically enhanced preprotachykinin mRNA in the shell of accumbens. This indicates that the two receptor subtypes may affect neurons in either synergy or opposition according to the cell or signal generated. Levodopa-induced behavioral sensitization in hemiparkinsonian rats is another example of D1/D3 receptor interaction. Hence repeated levodopa administration induces the ectopic appearance of the D3 receptor in substance P/dynorphin, striatonigral neurons of the dorsal striatum. This induction is secondary to D1 receptor stimulation in neurons of the denervated side and fully accounts for the sensitization, i.e. the increased behavioral responsiveness to levodopa. During brain development, a similar process could operate to control the late appearance of the D3 receptor in D1-receptor bearing neurons of the ventral striatum at a time at which they start to be innervated by dopamine neurons. Finally, taking into account a variety of genetic, developmental, neuroimaging and pharmacological data, we postulate that imbalances between the levels of D1 and D3 receptors in the same neurons could be responsible for schizophrenic disorders.
 ...
PMID:Functional implications of multiple dopamine receptor subtypes: the D1/D3 receptor coexistence. 965 37

These experiments tested the hypothesis that substance P neurotransmission at tachykinin NK1 receptors in the locus coeruleus is involved in stress-induced activation of the locus coeruleus, using c-fos as an index of activation. Selective tachykinin NK1 receptor antagonists administered systemically did not result in substantial locus coeruleus c-fos expression. Restraint stress resulted in a large number of locus coeruleus c-fos expressing cells. Administration of two selective tachykinin NK1 receptor antagonists prior to restraint resulted in an increase in the number of locus coeruleus c-fos expressing cells, compared to restraint alone. These results suggest that the enhanced c-fos expression observed in response to tachykinin NK1 receptor antagonists combined with stress, could be due to the blockade of tachykinin NK1 receptor-mediated activity at sites other than the locus coeruleus, resulting in an overall activation of the locus coeruleus.
 ...
PMID:Tachykinin NK1 receptor antagonists enhance stress-induced c-fos in rat locus coeruleus. 965 29

Using double in situ hybridization, we found extensive coexpression of dopamine D1 and D3 receptor (D1R and D3R) mRNAs in neurons of the island of Calleja major (ICjM) and ventromedial shell of nucleus accumbens (ShV), respectively. Thus, at least 79 and 63% of D3R mRNA-expressing neurons in ICjM and ShV also expressed the D1R mRNA. Coexpression of D1R and D3R mRNAs was found to occur in substance P (SP) mRNA-expressing neurons in both areas, suggesting SP mRNA as a marker of the activity of coexpressing neurons. Administration of SKF 38393, a D1R receptor agonist, increased c-fos mRNA in ICjM, whereas administration of quinpirole, a D2R/D3R agonist, decreased it; SCH 23390, a D1 R antagonist and nafadotride, a preferential D3R antagonist, given alone, had effects opposite to those of the corresponding agonists. These data indicate that basal c-fos expression in ICjM is maintained by endogenous dopamine acting tonically upon two receptor subtypes subserving opposite effects on the same cell. However, in ShV, whereas SKF 38393 also increased c-fos mRNA, quinpirole had no effect, a difference presumably reflecting the lower fraction of neurons coexpressing D1R and D3R in this area. In contrast, in ShV from reserpine-treated rats, SKF 38393 increased SP mRNA and quinpirole potentiated this effect. These contrasting interactions of D1R- and D3R-mediated signalling events, i.e. in either opposite or synergistic directions, most likely occurring at the single cell level, may serve to increase the dopamine response threshold of the target cells in ICjM and to maintain a strong tonic activity of ShV neurons.
 ...
PMID:Coexpression of dopamine D1 and D3 receptors in islands of Calleja and shell of nucleus accumbens of the rat: opposite and synergistic functional interactions. 975 Nov 40


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