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)

Receptor specificity of the substance P-related peptides neurokinin A and neurokinin B was studied in the isolated guinea pig ileum. Substance P and the recently discovered neurokinins elicit contraction of the ileum both directly through action on a muscle cell receptor and indirectly through stimulation of a neuronal receptor, leading to release of acetylcholine, which causes muscle contraction via muscarinic receptors. Two specific assay procedures for the function of the neuronal receptor were developed. The muscular receptor was inactivated either by desensitization with the selective agonist substance P methyl ester or by receptor blockade with the selective antagonist [Arg6, D-Trp7,9, Me-Phe8]substance P-(6-11) hexapeptide. Both procedures revealed that the neuronal receptor is clearly distinct from the muscular receptor, since it exhibits different agonist specificity and is insensitive to antagonists of the muscular receptor. Neurokinin B was found to be the most potent agonist (EC50 = 1 nM) for the neuronal receptor. Furthermore, [D-Ala2, Met5]enkephalinamide inhibited in a naloxone-sensitive manner the effect of neurokinin B mediated via the neuronal receptor. These results suggest that the different mammalian tachykinins can play specific physiological roles by virtue of their distinct receptor specificities.
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PMID:Neurokinin B is a preferred agonist for a neuronal substance P receptor and its action is antagonized by enkephalin. 241 77

The occurrence of tachykinins in sensory neurons of the guinea-pig was studied by means of radioimmunoassay combined with ion-exchange and high-performance liquid chromatography as well as by immunohistochemistry. Antisera raised against kassinin (antiserum K12), neurokinin A (NKA) (antiserum NKA2) and substance P (SP) (antisera SP25 and SP2) were used. Antiserum K12 detected NKA, neuropeptide K (NPK) and a component eluting in the position of eledoisin (ELE) in extracts of the lung and ureter. Neurokinin B (NKB) was, however, not found. Neutral water extraction favored recovery of NKA and of the ELE-like component, while NPK was found only in acid extracts. The SP antisera detected two immunoreactive components of which the major form coeluted with synthetic SP. Capsaicin pretreatment depleted all these various forms of immunoreactivity in several peripheral organs including the ureter and lung. The immunoreactivity detected by antisera K12 or SP25 in radioimmunoassay had a similar regional distribution pattern in peripheral tissues. Immunohistochemical examination revealed that antiserum NKA2 stained the same spinal ganglion cells as the SP2 antiserum. The distribution of capsaicin-sensitive nerve fibers stained by these two antisera was also identical in peripheral organs such as the ureter, inferior mesenteric ganglion, heart and lung. It is concluded that multiple tachykinins, including SP, NKA, NPK and an ELE-like peptide, are present in capsaicin-sensitive sensory nerves in the guinea-pig. This finding can most likely be related to the origin of SP, NKA and NPK from the same precursor molecule, subsequent posttranslational tissue processing and axonal transport to terminal regions.
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PMID:Multiple tachykinins (neurokinin A, neuropeptide K and substance P) in capsaicin-sensitive sensory neurons in the guinea-pig. 241 71

We have studied the selectivity and competitiveness of three neurokinin antagonists and atropine against substance P, neurokinin A, and neurokinin B. DPDTNLE-NB, [D-Pro2, D-Trp6,8, Nle10]-neurokinin B is a competitive antagonist of neurokinin B (pA2 = 5.5), but not substance P or neurokinin A. DPDT-SP ([D-Pro2,Trp7,9]-substance P), competitively blocks substance P (pA2 = 6.9) and neurokinin B (pA2 = 6.8), but not neurokinin A. Spantide ([D-Arg1, D-Trp7,9, Leu11]-substance P) competitively blocks substance P (pA2 = 6.7) and at a log unit higher concentration blocks neurokinin A (pA2 = 5.8), but does not block neurokinin B. Atropine is a competitive antagonist of neurokinin B (pA2 = 9.0) at ten times the concentration needed to block acetylcholine (pA2 = 10.1), but does not inhibit the other neurokinins. These results support the hypothesis of multiple neurokinin receptors in the guinea pig ileum and indicate that the site of neurokinin B, but not substance P or neurokinin A is predominantly on intramural neurons. This indirect stimulation appears to be dependent on the release of acetylcholine. Neurokinin B also has activity on smooth muscle receptors since the contractile response could not be completely antagonized by atropine. There appear to be two smooth muscle neurokinin receptors on the basis of results obtained with DPDT-SP and spantide, one predominantly responsive to substance P and the other to neurokinin A. Only spantide appeared to have any effect on the neurokinin A receptor and that was at a much higher concentration than that needed to block substance P.
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PMID:Differentiation of multiple neurokinin receptors in the guinea pig ileum. 243 Dec 45

Behavioural responses to tachykinins were observed following intracisternal administration in mice. The synthetic NK-3 agonists senktide and L-363,851 caused behaviour typically associated with serotonergic stimulation, including head twitches, reciprocal forepaw treading and hindlimb splaying. Neurokinin B produced some features of the serotonin (5-HT) syndrome, while substance P, neurokinin A and eledoisin failed to elicit any such behaviours. Senktide-induced head twitches were prevented by pretreatment with the 5-HT2 antagonists ketanserin and ritanserin, while forepaw treading was attenuated by the 5-HT1 antagonists (-)-pindolol and methysergide. These data suggest that NK-3 agonists interact with central 5-HT mechanisms.
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PMID:Senktide, a selective neurokinin B-like agonist, elicits serotonin-mediated behaviour following intracisternal administration in the mouse. 244 14

The mammalian tachykinins substance P (SP) and neurokinin A (NKA) are known to be present in sensory airway nerves of animals and humans. We studied the effect of mammalian and nonmammalian tachykinins on the conducting airways of anesthetized, mechanically ventilated Fisher 344 rats. Dose-dependent increases in lung resistance and decreases in dynamic compliance occurred after the intravenous administration of eledoisin (E), kassinin (K), NKA, and SP. E, K, and NKA were more potent bronchoconstrictors than was SP. Neurokinin B (NKB) caused a similar decrease in dynamic compliance, but had no effect on lung resistance. This order of potency suggests a predominance of NK-2 receptors in the rat airways. Both atropine and the 5-hydroxytryptamine antagonist methysergide largely reduced the bronchoconstriction induced by E and SP. Vagotomy did not change this reaction, whereas pretreatment with the ganglion blocker hexamethonium slightly enhanced the bronchoconstrictor action of E and SP. Sodium cromoglycate and nedocromil sodium, 2 drugs that can inhibit mediator release from inflammatory cells, significantly reduced the bronchoconstrictor action of NKA. Ketotifen, an antihistamine with mast-cell-stabilizing properties, significantly reduced the bronchoconstriction induced by E, whereas the H1-receptor antagonist clemastine had no effect. We conclude that tachykinins cause bronchoconstriction in rats largely by an indirect mechanism, involving both acetylcholine and 5-hydroxytryptamine. We suggest that tachykinins cause bronchoconstriction by stimulation of postganglionic vagal nerve endings and mast cells.
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PMID:The mechanism of tachykinin-induced bronchoconstriction in the rat. 246 68

Mapping and cortical projections of neurons containing neurokinin B (NKB) mRNA in the rat basal forebrain were studied using hybridization histochemistry and retrograde labeling. Neurokinin B mRNA was found in a small proportion of the neurons present in the magnocellular basal nucleus that project to the cortex. Most of these neurons projected to the frontal and parietal cortices, whereas only few projected to the occipital cortex and almost none to allocortical areas, including the olfactory bulb. NKB mRNA colocalization with galanin or substance P mRNAs, both found within neurons of the magnocellular basal nucleus, was not detected there. These results demonstrate a novel diffuse neocortical tachykinin input from the basal forebrain, in addition to the well-known cholinergic one.
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PMID:Neurons with neurokinin B mRNA in the rat magnocellular basal nucleus: distribution, projection and colocalization studies. 247 59

Neurons containing transcripts encoding neurokinin B, a member of the tachykinin family, were studied in the rat caudate-putamen using hybridization histochemistry. Neurons containing neurokinin B mRNA were distributed throughout the caudate-putamen, with a slightly higher density in the middle portions as compared with the more rostral and caudal portions. These neurons were either isolated, often located close to neurons devoid of neurokinin B mRNA, or in small clusters of three to 10 cells. A larger group of neurons with neurokinin B mRNA was seen in the ventrolateral caudate-putamen, near the tip of the external capsule. Neurokinin B mRNA was colocalized in neurons with substance P (59% of neurokinin B neurons had substance P mRNA) and with enkephalin mRNA (25% of neurokinin B neurons had enkephalin mRNA). After injections of the fluorescent dye Fluorogold into the globus pallidus and substantia nigra, retrograde axonal transport studies demonstrated neurokinin B mRNA in striatopallidal but not striatonigral projections. The influence of dopaminergic input on the level of neurokinin B mRNA in the caudate-putamen was studied after 6-hydroxydopamine lesions of the substantia nigra/ventral tegmental area. Both the number of cells detected containing neurokinin B mRNA as well as the level of transcripts per cell increased on the side ipsilateral to the lesion, whereas the opposite was seen on the contralateral side. These results describe a novel neurochemical system within the rat basal ganglia that is regulated by dopaminergic innervation from the mesencephalon.
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PMID:Distribution, projection and dopaminergic regulation of the neurokinin B mRNA-containing neurons of the rat caudate-putamen. 247 82

[3H]Neurokinin B ([3H]NKB) of high specific activity (75 Ci/mmol) was synthesized for study of its binding to crude synaptosomes from the rat cerebral cortex. The specific binding of [3H]NKB (75% of total binding) was temperature dependent, saturable, and reversible. Scatchard analyses and Hill plots showed the existence of a single population of noninteracting binding sites (KD = 4.3 nM; Bmax = 123 fmol/mg of protein). Competition studies indicated the following rank order of potencies among tachykinins: NKB greater than eledoisin (E) greater than kassinin greater than physalaemin greater than neurokinin A (NKA) greater than substance P (SP), a result suggesting that NKB might be the endogenous ligand for [3H]NKB binding sites. It is of interest that 127I-Bolton Hunter (BH) NKA (127I-BHNKA) was much more potent than NKA in inhibiting the specific binding of [3H]NKB, which raises certain questions concerning the use of 125I-BHNKA as a ligand for NKA binding sites in the brain. These results, as well as those obtained with different SP analogues, show a close similarity to those obtained previously with 125I-BHE binding to cortical synaptosomes. This suggested that the two ligands labeled identical binding sites. In addition, using either [3H]NKB or 125I-BHE as ligands, similar displacement curves were obtained with increasing concentrations of NKB and 127I-BHE. The similarity of the [3H]NKB and 125I-BHE binding sites was further confirmed by comparison of their localization on rat brain sections by autoradiography. The distribution of binding sites for [3H]NKB and 125I-BHE was identical throughout the brain, and the highest density of binding sites for the two ligands was found in layers IV and V of the cerebral cortex, the paraventricular nucleus of the hypothalamus (magnocellular part), and the ventral tegmental area.
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PMID:[3H]neurokinin B and 125I-Bolton Hunter eledoisin label identical tachykinin binding sites in the rat brain. 302 61

Substance P (3 micrograms/kg), neurokinin A (20 micrograms/kg), neurokinin B (6 micrograms/kg) and acetylcholine (875 micrograms/kg) all produced salivation upon i.v. infusion in the anesthetized rat. Against single equivalent agonist doses, atropine (135 micrograms/kg i.v.) blocked both acetylcholine- and neurokinin B-, but not substance P- or neurokinin A-induced salivation. [D-Pro2,D-Trp7,9]-substance P (1 mg/kg i.v.), a putative substance P antagonist, reduced responses to mammalian neurokinins but caused a 2-fold potentiation of acetylcholine-induced salivation. [D-Pro2,D-Trp6,8,Nle10]-Neurokinin B (1 mg/kg i.v.), a novel putative neurokinin B antagonist, significantly reduced substance P- and neurokinin B- but not acetylcholine- or neurokinin A-induced salivation. The three agonists (at doses that produced salivation) and [D-Pro2,D-Trp6,8,Nle10]-neurokinin B (1 mg/kg i.v.) lowered blood pressure in anesthetized rats by 35 to 40%. [D-Pro2,D-Trp7,9]-Substance P (1 mg/kg i.v.) had no significant effect on blood pressure. Hydralazine at 0.60 mg/kg (i.v.), a dose which lowered blood pressure by 47%, did not reduce substance P-induced salivation. Thus, blockade of neurokinin-induced salivation by [D-Pro2,D-Trp6,8,Nle10]-neurokinin B was probably not due to hypotension. Based on the differential effects of the three antagonists on neurokinin- and acetylcholine-induced salivation, we hypothesize the existence of three distinct neurokinin receptors in rat salivary gland, and suggest that neurokinin B receptors reside presynaptically.
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PMID:Neurokinin-induced salivation in the anesthetized rat: a three receptor hypothesis. 303 19

The rat isolated portal vein is a pharmacological preparation more sensitive to neurokinin B than to any other neurokinin or tachykinin. The preparation is more sensitive to C-terminal partial sequences of substance P (SP) particularly SP-(6-11) than to the whole undecapeptide. The order of potency of neurokinins is as follows: neurokinin B greater than neurokinin A greater than substance P. The preparation shows high sensitivity also to kassinin and eledoisin. Comparative tests performed with strips of the rat portal vein suspended in a microbath under continuous perfusion (system 1) or in ordinary baths for isolated smooth muscles (system 2) have given similar results and have shown that the myotropic effect of neurokinin B is not modified by a variety of antagonists of endogenous agents as well as by inhibitors of the arachidonic acid cascade. The present results suggest that neurokinin B contracts the rat portal vein by activating specific receptors, presumably located on the smooth muscle membrane, different from those of biologically active amines and peptides which are active stimulants of the vein. Neurokinin B is ten times more active than neurokinin A and at least 100 times more than substance P. Such an order of potency of agonists suggests the existence of a new neurokinin receptor type, particularly sensitive to neurokinin B.
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PMID:The rat isolated portal vein: a preparation sensitive to neurokinins, particularly neurokinin B. 347 18


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