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 binding of iodine-labeled Bolton-Hunter substance P (125I-BHSP) to porcine endothelial cell membranes was examined. The endothelial cells had a single high-affinity binding site with a dissociation constant of 0.10 nM, and a maximum number of binding sites of 52.2 fmol/mg protein. The relative potencies of various tachykinins to displace the binding of 47 pM 125I-BHSP suggested that endothelial cells of porcine aorta contain the NK-1 subtype of tachykinin receptor. A GTP analogue, guanyl-5'-yl imidodiphosphate, induced marked reduction in the number of 125I-BHSP binding sites suggesting that these binding sites are coupled with GTP-binding protein.
 ...
PMID:Characterization of tachykinin receptors in endothelial cells of porcine artery. 169 73

1. Multiple distinct affinity states or sites of substance P (SP) receptors exist in freshly-prepared rat brain membranes. 2. Substance P receptors may couple with islet-activating protein (pertussis toxin) sensitive GTP-binding protein(s). 3. Substance P receptors may be regulated Mg2+ and Na+ in an opposite manner. 4. Some important factor(s), in addition to GTP-binding protein, appear to be involved in SP binding activity. 5. An apparent molecular weight of the SP binding site is approximately 46,000 Da.
 ...
PMID:Substance P receptors in mammalian central nervous system. 170 76

Substance P (SP) stimulates polyphosphoinositide breakdown in the rat anterior pituitary through an NK-1 receptor. In the present study we present evidence that the coupling between the SP-NK1 receptor complex and polyphosphoinositide-specific phospholipase C (PI-PLC) in rat anterior pituitary membranes may involve a mechanism consistent with a GTP-binding protein. The formation of inositol phosphates from [3H]myo-inositol-labelled anterior pituitary membranes induced by SP was potentiated by GTP and non-hydrolysable guanine nucleotides. The stimulatory effects of SP alone and SP plus GTP could be blocked by addition of GDP-beta-S (guanosine 5-O-(thiodiphosphate] in excess. Basal and SP plus guanine nucleotide-induced inositol phosphate formation were stimulated by fluoride, whereas the effect of SP alone was inhibited. Pretreatment of anterior pituitary membranes with sodium deoxycholate attenuated the inositol phosphate response elicited by GTP and GTP-gamma-S, whereas basal and SP-stimulated inositol phosphate production showed a peak at 1 mg sodium deoxycholate/ml. SP, fluoride and guanine nucleotide stimulatory effects on hydrolysis of polyphosphoinositide (PPI) were unaffected by pretreatment of anterior pituitary cells with cholera or pertussis toxin for 12h. Treatment of anterior pituitary membranes with cholera and pertussis toxin yielded [32P]ADP-ribosylation of two proteins with molecular masses of 45 and 41 kDa respectively. We conclude that SP coupling to PI-PLC through the NK1 receptor in the rat anterior pituitary involves a GTP-binding mechanism distinct from the G-proteins associated with adenylate cyclase, Gs and Gi.
 ...
PMID:Substance P stimulation of polyphosphoinositide hydrolysis in rat anterior pituitary membranes involves a GTP-dependent mechanism. 171 80

The modulation of Ca2+ currents by neurotransmitters was studied in freshly dissociated rat spinal cord neurons, using the whole-cell patch-clamp technique. GABA, baclofen, adenosine, ATP, serotonin, norepinephrine, somatostatin, and dynorphin A inhibited the current through Ca2+ channels in a substantial fraction of cells, while substance P, vasoactive intestinal polypeptide, [D-ala2,d-leu5]-enkephalin, cholecystokinin-8 (sulfated), calcitonin gene-related peptide, angiotensin II, neurotensin, vasopressin, and thyrotropin-releasing hormone had no effect. In the case of baclofen, the inhibition is mediated, at least in part, by a GTP-binding protein. Suppression of Ca2+ current by neurotransmitters may represent a mechanism of presynaptic inhibition in the spinal cord.
 ...
PMID:Neurotransmitter modulation of calcium current in rat spinal cord neurons. 196 36

Neurokinin A (substance K) is a peptide neurotransmitter of the tachykinin family with potential as a major mediator in human airway and gastrointestinal tissues. Neurokinin A acts via a receptor (the NK-2 receptor) believed to be localized on smooth muscle cells and pharmacologically coupled to a GTP-binding protein. To characterize the human NK-2 receptor, we prepared a partial cDNA from human tracheal RNA using the polymerase chain reaction with oligonucleotide primers derived from the bovine NK-2 receptor cDNA sequence (Masu, Y., Nakayama, K., Tamaki, H., Harada, Y., Kuno, M., Nakanishi, S. (1987) Nature 329, 836-838). This partial human NK-2 receptor cDNA was used to screen a human genomic DNA library and yielded a clone, NGNK-2, of approximately 25 kilobases. Analysis of NGNK-2 indicates that it contains the entire coding sequence of the NK-2 receptor as well as 5'- and 3'-flanking sequences. The gene is organized with five exons interrupted by four introns. The complete sequence of the exons and the intron-exon junctions was determined, as were the transcription initiation site and the 3'-polyadenylation signal. Analysis of EcoRI digests of genomic DNA from human-mouse cell hybrids indicates a single gene for the human NK-2 receptor localized to chromosome 10. Sequence analysis of exons 1 and 5, where major differences occur between the human and animal species, provided information for polymerase chain reaction primers which allowed us to prepare full-length cDNA for the human NK-2 receptor. The protein predicted from the gene sequence is extended by 14 amino acids at the COOH terminus compared to the bovine and 9 residues compared to the rat molecules. The seven membrane-spanning regions are encoded by exons 1-4 and none is interrupted by introns. These regions are highly conserved among the species studied, suggesting stringent evolutionary control over these molecules.
 ...
PMID:The human neurokinin A (substance K) receptor. Molecular cloning of the gene, chromosome localization, and isolation of cDNA from tracheal and gastric tissues. 184 90

Modulation of the voltage-gated K+ conductance in T-lymphocytes by substance P was examined. Whole-cell recordings from JurkaT E6-1 human T-lymphocytes revealed two components of substance P action on the outward K+ current: (i) dose- and time-dependent reduction of current peak amplitude; and (ii) acceleration of the current inactivation rate. This action was blocked by substituting Cs+ for K+ in the recording pipette and by the substance P antagonist. [D-Arg1, D-Phe5, D-Trp7,9, Leu11]-substance P. As indicated by conductance-voltage relationship, the reduction in current peak amplitude as a result of substance P application was not due to a shift of the voltage dependence of the channel. Raising intracellular free calcium concentration from 2 to 200 nM reversed the reduction, induced by substance P, in current peak amplitude and disclosed an apparent desensitization towards the neuropeptide action. The treatment, however, did not reverse substance P-induced acceleration of the rate of current decay. Intracellular administration of hydrolysis-resistant guanosine triphosphate (to persistently activate GTP-binding protein) and guanosine diphosphate (to competitively inhibit GTP-binding proteins) analogues mimicked and inhibited substance P-induced reduction of K+ conductance, respectively. The data demonstrate a modulation of T-lymphocyte K+ channels by substance P and substantiate a possible role for GTP-binding proteins in this modulation.
 ...
PMID:Modulation of membrane K+ conductance in T-lymphocytes by substance P via a GTP-binding protein. 248 61

1. To study the regulation of calcium influx in non-excitable cells, membrane currents of rat peritoneal mast cells were recorded using the whole-cell patch-clamp technique. At the same time, intracellular calcium concentration ([Ca2+]i) was monitored via the fluorescent calcium-indicator dye Fura-2, which was loaded into cells by diffusion from the patch pipette. 2. Stimulation of mast cells with secretagogues, such as compound 48/80 or substance P, caused release of Ca2+ from internal stores. In addition, external agonists also induced influx of external calcium in 26% of the cells investigated. The agonist-stimulated Ca2+ influx was increased during membrane hyperpolarization and was associated with small whole-cell currents. 3. Likewise, internal application of inositol 1,4,5-trisphosphate (Ins1,4,5P3:0.5-10 microM) elevated [Ca2+]i due both to release of Ca2+ from internal stores and to influx of external calcium. The Ins1,4,5P3-induced influx was greater at more negative membrane potentials, suggesting that Ins1,4,5P3 opened a pathway through which calcium could enter at a rate governed by its electrochemical driving force. 4. Inositol 1,3,4,5-tetrakisphosphate (Ins1,3,4,5P4) did not induce Ca2+ influx by itself nor did it facilitate or enhance Ins1,4,5P3-induced Ca2+ entry. Calcium influx was also induced by inositol 2,4,5-trisphosphate. Since this inositol phosphate is a poor substrate for Ins1,4,5P3 3-kinase it seems unlikely that Ins1,3,4,5P4 plays a role in the regulation of the Ca2(+)-influx pathway in mast cells. 5. The Ins1,4,5P3-induced Ca2+ influx was associated with whole-cell currents of 1-2 pA or less, with no channel activity detectable in whole-cell recordings. The small size of the whole-cell current suggests either that the Ins1,4,5P3-dependent influx occurs via small-conductance channels that are highly calcium specific or that the influx is not via ion channels. 6. Agonist stimulation also activated large-conductance (ca 50 pS) cation channels, through which divalent cations could permeate; thus, these channels represent a second pathway for Ca2+ influx. The slow speed of activation of the channels by agonists, their activation by internal guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S), and the inhibition of agonist activation by internal guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S) all suggest that the 50 pS channels are regulated by a second messenger and/or a GTP-binding protein. The activity of the 50 pS channel in mast cells is not sensitive to either Ins1,4,5P3 or Ins1,3,4,5P4. Activity of the channel was inhibited by elevated [Ca2+]i.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Second messenger-activated calcium influx in rat peritoneal mast cells. 255 68

1. The effect of octopamine on the release of endogenous acetylcholine (ACh) from isolated ileal synaptosomal preparations of guinea-pigs was examined using high pressure liquid chromatography with electrochemical detection. Release of ACh was induced by substance P or by depolarization with high potassium (50 mmol/L) in medium containing atropine, propranolol and naloxone. 2. Octopamine produced a dose-dependent inhibition of substance P-induced ACh release. A similar inhibitory action of octopamine was found in the samples depolarized by high potassium as a reference. 3. The action of octopamine was not reversed by the dopamine receptor antagonists either for the DA-2 subtype, domperidone, or for the DA-1 subtype, SCH23390, or by haloperidol. However, idazoxan and yohimbine antagonized this octopamine-induced inhibition at concentrations sufficient to abolish the action of clonidine. 4. Failure of guanethidine or nomifensine to inhibit octopamine ruled out mediation by noradrenergic neurotransmitters. 5. Octopamine decreased the influx of [45Ca] stimulated by substance P into synaptosomal preparations and this was reversed by idazoxan or yohimbine at concentrations sufficient to block the action of clonidine. 6. Pertussis toxin abolished the inhibitory action of octopamine at a dose high enough to block the action of clonidine. 7. These results indicate that octopamine suppresses the influx of calcium ions into cholinergic nerve terminals of ileal synaptosomes of guinea-pigs via an activation of alpha 2-adrenoceptors coupled with a pertussis toxin-sensitive GTP-binding protein which results in a decrease of ACh release.
 ...
PMID:Inhibitory effect of octopamine on the release of endogenous acetylcholine from isolated myenteric synaptosomes of guinea-pig. 750 51

1. The effect of exogenous dopamine on the release of endogenous acetylcholine (ACh) from isolated ileal synaptosomal guinea-pig preparations was examined by means of high pressure liquid chromatography with electrochemical detection. 2. Release of ACh was induced by substance P or by depolarization with high potassium (50 mM) in a medium containing atropine propranolol and naloxone. 3. Dopamine produced a concentration-dependent inhibition of the evoked ACh release induced by substance P or in samples depolarized by high potassium. This action of dopamine was not reversed by the dopamine receptor antagonists either for the DA2 subtype domperidone, or for the DA1 subtype, SCH23390. Fenoldopam, the agonist of dopamine DA1 receptors, or quinpirole, the agonist of dopamine DA2 receptors, reduced the evoked ACh release, although only in high, non-dopamine-specific concentrations. 4. Failure of guanethidine or desipramine to inhibit this effect of dopamine ruled out mediation by endogenous noradrenaline. 5. Idazoxan and yohimbine reversed this dopamine-induced inhibition at concentration sufficient to abolish the action of clonidine. Influx of (45)Ca stimulated by substance P or high potassium into synaptosomal preparations was attenuated in the presence of dopamine. This inhibition by dopamine was also reversed by idazoxan or yohimbine but not by dopamine receptor antagonists. Moreover, the dopamine-induced inhibitions of both the ACh release and the influx of (45)Ca disappeared in the samples treated with pertussis toxin at a dose sufficient to abolish the action of clonidine. 6. It is concluded that dopamine suppresses the influx of calcium ions into cholinergic nerve terminals via an activation of alpha2-adrenoceptors coupled with a pertussis toxin-sensitive GTP-binding protein, resulting in the decrease of ACh release from ileal synaptosomes of guinea-pigs.
 ...
PMID:Dopamine-induced inhibition of endogenous acetylcholine release from the isolated ileal synaptosomal preparations of guinea-pig mediated via alpha-adrenoceptors. 752 17

Incubation of bovine hippocampal membranes with [alpha-32P]GTP and exposure to ultraviolet light resulted in the labelling of seven species with apparent molecular masses of 200, 74, 55, 53, 50, 43 and 40 kDa. Labelling of the 55 kDa species was greatly enhanced in the presence of carboxyl terminal fragments [neuropeptide Y-(18-36)] of neuropeptide Y. Labelling occurred with [alpha-32P]GTP but not [alpha-32P]ATP. A group of putative direct G protein activating peptides including mastoparan, melittin, substance P and adrenocorticotropic hormone (ACTH)-(1-24), were also able to stimulate the labelling of this protein. Labelling of the 55 kDa protein could be demonstrated in bovine brain but not peripheral tissues. Western blot analysis using an antibody against the common alpha subunit of G proteins recognized a protein co-migrating with the 55 kDa GTP-binding protein. These findings demonstrate the existence of a previously uncharacterized neuronal protein, with an apparent molecular mass of 55 kDa, that binds GTP in response to neuropeptide Y and other peptides.
 ...
PMID:Neuropeptide Y promotes GTP photo-incorporation into a 55 kDa protein. 780 55


1 2 Next >>