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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurokinins and their receptors are a complex system consisting of at least three endogenous agents--substance P (SP), neurokinin A (NKA), and neurokinin B (NKB)--and their corresponding receptor types, respectively, NK-1, NK-2, and NK-3. Investigations on receptors have been made using sensitive and fairly selective pharmacological preparations (the dog carotid artery for the NK-1, the rabbit pulmonary artery devoid of endothelium for the NK-2, and the rat portal vein for the NK-3 receptor), and some natural peptides of mammalian and nonmammalian origin. Because of the nonselectivity of the natural peptides, analogues of the neurokinins have been found that act on one receptor only and show therefore high selectivity. The selective agonists [Sar9,Met(O2)11]SP, [Nle10]NKA (4-10), and [MePhe7]-NKB have been used successfully for (a) characterizing the three neurokinin receptors, (b) identifying isolated organs whose responses to neurokinins depend on the activation of a single (monoreceptor systems) or of more than one (multireceptor systems) receptor, and (c) elucidating some of the physiological function of the three receptor types. It is suggested that NK-1 mediate peripheral vasodilatation and exocrine secretions, NK-2 stimulate bronchial muscles and facilitate the release of catecholamines, and NK-3 promote the release of acetylcholine in peripheral organs.
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PMID:Selective agonists for receptors of substance P and related neurokinins. 247 Apr 40

Unilateral removal of the afferent fibers of the IXth and Xth cranial nerve (nodose ganglionectomy) caused significant decrease in the content of substance P-like immunoreactivity (SP-LI) and neurokinin A-like immunoreactivity (NKA-LI) in the nucleus tractus solitarii (NTS) of rats. Microinjection of SP (1 ng) or NKA (10-100 ng) into the NTS caused prompt, transient hypotension and bradycardia, suggesting that SP and NKA may be neurotransmitters of the baroreceptor reflex in the NTS. NKB-like immunoreactivity (NKB-LI) was also detected in the NTS of rats by radioimmunoassay, but its content in the NTS was not affected by unilateral nodose ganglionectomy. The microinjection of 1-10 ng of suc-[Asp5, Me-Phe8]-SP(6-11) (senktide, a selective neurokinin B receptor peptide) into the NTS caused long-lasting hypertension and tachycardia. These results indicate that NKB may also be a neuromodulator on cardiovascular responses in the NTS.
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PMID:Cardiovascular roles of tachykinin peptides in the nucleus tractus solitarii of rats. 247 79

(1) Longitudinal muscle strips from the human small intestine (jejunum/ileum) responded to electrical field stimulation (1-50 Hz) with frequency-related primary contractions which were largely atropine- (3 microM) sensitive. When the tone was raised by addition of galanin (0.3-1 microM), prostaglandin (PG) E2 (1-10 microM) or neurokinin A (NKA, 0.1 microM), a frequency-related relaxation was evident which was potentiated by atropine. All the responses to field stimulation were abolished by tetrodotoxin (1 microM), thus indicating their neural origin. (2) The atropine-sensitive primary contraction to field stimulation was virtually abolished by omega conotoxin fraction GVIA (CTX, 0.1-0.3 microM) while the relaxations were CTX-resistant. The field stimulation-induced relaxations, which were observed in the presence of atropine and guanethidine (3 microM), were also unaffected by apamin (0.1 microM). (3) NKA and substance P (SP) produced a concentration- (1 nM-1 microM for both peptides) related contraction, NKA being about 53 times more potent than SP. [Pro9]SP sulphone and [MePhe7]-NKB, selective agonists of the NK-1 and NK-3 receptor, respectively, were barely effective. On the other hand, [beta Ala8]NKA(4-10), a selective NK-2 receptor agonist, had a potent contractile activity, similar to that of NKA. (4) Galanin (1 nM-1 microM) produced an atropine- and tetrodotoxin-resistant concentration-related contraction of longitudinal muscle of human isolated small intestine. The response to galanin did not show any sign of fading and was particularly suitable to study the evoked relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human isolated small intestine: motor responses of the longitudinal muscle to field stimulation and exogenous neuropeptides. 247 55

Cultured astrocytes from rat cortex and spinal cord responded with different types of membrane potential changes upon brief (10 seconds) applications of the natural neurokinin agonists substance P and neurokinin A. The most prominent type of response was a long-lasting membrane depolarization. In some cells, an initial rapid depolarization followed by a partial repolarization preceded the slow depolarizing event. Few astrocytes responded with a hyperpolarization of the membrane. Selective agonists at the NK-1 receptive site, substance P-methyl ester (SP-OME) and septide, mimicked the response to the natural neurokinins as did DiMe-C7, a selective NK-3 receptor agonist. A putative neurokinin antagonist, (D-Arg1,D-Pro2,D-Trp7,9,Leu11)SP (DADPDT) partially blocked membrane potential responses induced by substance P, SP-OME, septide, DiMe-C7, and NKA. The authors conclude that astrocytes express NK-1 and NK-3 receptors, which upon activation affect the electrical properties of these cells.
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PMID:Activation of substance P receptors leads to membrane potential responses in cultured astrocytes. 247 32

1. Intravenous administration of three mammalian tachykinins (substance P, neurokinin A and neurokinin B) and three non-mammalian tachykinins (physalaemin, eledoisin and kassinin) induced dose-dependent increases in vascular permeability, as measured by Evans blue leakage technique, in various segments of the lower urinary tract (bladder dome and neck, proximal urethra, ureters) in urethane-anaesthetized rats. 2. Plasma extravasation induced by substance P (3.71 nmol kg-1 i.v.) was unaffected by pretreatment with antihistaminic drugs or methysergide. 3. A comparison of the relative potencies of various tachykinins did not allow characterization of a distinct type of receptor involved in the increase in vascular permeability. 4. The effects of tachykinin-related peptides which are selective agonists at the NK-1 (substance P-methylester, [Pro9]-SP-sulphone), NK-2 receptor [( Nle10]-NKA(4-10] or NK-3 receptor [( MePhe7]-NKB(4-10) and Senktide) indicated that NK-1 agonists are effective in the whole lower urinary tract, while NK-2 or NK-3 agonists are inactive or weakly active. 5. [beta-Ala4, Sar9]-SP(4-11)-sulphone, a selective NK-1 receptor agonist devoid of histamine-releasing properties, was highly potent and effective in producing plasma extravasation in the rat lower urinary tract. 6. These findings indicate that NK-1 receptors mediate the effect of intravenous tachykinins on vascular permeability in the rat lower urinary tract, through a histamine-independent mechanism.
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PMID:Effects of tachykinins and selective tachykinin receptor agonists on vascular permeability in the rat lower urinary tract: evidence for the involvement of NK-1 receptors. 247 7

Sensitive afferent nerves and the neurokinins they release upon activation are considered to be important in controlling bronchomotor tone. Human isolated bronchi respond to neurokinin A (NKA), substance P (SP), and neurokinin B (NKB) with dose-dependent contractions. The order of potency of the three natural neurokinins is NKA greater than SP greater than NKB, suggesting the presence of NK-2 receptors. To further characterize the neurokinin receptors in human bronchi, we used selective agonists for each receptor type (i.e., NK-1, NK-2, and NK-3). In fact, NK-1 selective compounds, [Pro9]SP(1-11) sulfone and [beta-ala4,Sar9]SP(4-11) sulfone, did not induce significant contractions up to 10(-5) M. Similarly, the selective agonist for the NK-3 receptor, [MePhe7]NKB(4-10), was almost inactive. However, the NK-2 selective fragment [Nle]NKA(4-10) was a potent stimulant. The negative log of the peptide concentration that caused 50% of maximal effect (pD2) was 6.99 for NKA and 6.12 for [Nle10]NKA(4-10). Removal of the epithelium significantly enhanced the contractile responses to the three neurokinins and also to the NK-2 selective agonist. Phosphoramidon, an enkephalinase inhibitor, was more potent than epithelium removal in enhancing the contractile responses to these agonists. However, epithelium removal and phosphoramidon did not increase the weak responses to the NK-1 and NK-3 selective compounds. In the presence of phosphoramidon, removal of the epithelium slightly enhanced the contractile responses to NKA and [Nle]NKA(4-10) but not to SP and NKB.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of neurokinin effects and receptor selectivity in human isolated bronchi. 247 56

The regional distributions of neurokinin B-like immunoreactivity and substance P-like immunoreactivity in the central nervous system in spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs) were examined. The distribution of neurokinin B-like immunoreactivity in WKYs was not exactly the same as that of substance P-like immunoreactivity. The neurokinin B-like immunoreactivity contents of the supraoptic nucleus of the hypothalamus and the caudal part of the nucleus tractus solitarii were higher in SHRs than in WKYs. Injections of selective neurokinin B receptor peptides, senktide (suc-[Asp6,Me-Phe8]-substance P6-11) and [Pro7]-neurokinin B, into the lateral brain ventricle of the normotensive rats caused dose-dependent increases in the blood pressure, and blockade of peripheral vascular vasopressin receptors reduced these pressor responses, but did not affect the substance P-induced pressor response. These findings suggest that the novel tachykinin peptide, neurokinin B has an important role in central pressor action in rats.
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PMID:Central pressor actions of neurokinin B: increases in neurokinin B contents in discrete nuclei in spontaneously hypertensive rats. 247 57

1. Rat spinal cord neurones grown in tissue culture were used to examine the electrophysiological effects of the neurokin in (NK)-selective agonists (pGlu6, Pro9) substance P(6-11) (septide; NK1, 10(-6)M) and (pGlu5, MePhe8, MeGly9)SP(1-7) (DiMe-C7; NK3, 10(-6)M). In addition, the effect of the neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP (10(-5)M) on the neurokinin-evoked responses was investigated. 2. Neurokinin-evoked responses consisted of an increase in neuronal activity with or without long-lasting (mean: 50s) depolarizations of the membrane potential of up to 25mV. The latter also occurred in the presence of tetrodotoxin (10(-7)M) (direct response). 3. In a number of spinal cord neurones (n = 17) only septide induced a membrane depolarization while DiMe-C7 elicited no response. On the other hand, in 2 neurones a response was exclusively evoked by DiMe-C7. 4. The neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP had no effect of its own but blocked the septide- and DiMe-C7-induced depolarizations. It had no effect on the glutamate (10(-5)M)-evoked depolarization. 5. It is concluded that by the use of neurokinin receptor-selective agonists, subpopulations of spinal cord neurones in primary dissociated cell culture can be differentiated which express the NK1 or the NK3 receptor. Cells expressing only the NK1 receptor outnumber those expressing only the NK3 receptor subtype. Both receptors can be blocked by the neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP.
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PMID:Effects of receptor-selective neurokinin agonists and a neurokinin antagonist on the electrical activity of spinal cord neurones in culture. 248 Jan 70

The nonmammalian (eledoisin, kassinin and physalaemin) and mammalian tachykinins (substance P and neurokinin (NK) A), as well as the metabolically stable neurokinin analogs, DiMe-C7 [( pGlu5, MePhe8, Sar9]substance P (5-11)] and senktide, were infused into the median raphe nucleus of rats via chronically implanted cannulas, and their effects on locomotor activity analyzed. The NK-3 receptor agonists, senktide and DiMe-C7, as well as the endogenous NK-2 receptor ligand, NKA, produced dose-dependent increases in locomotor activity. Substance P, eledoisin, kassinin and physalaemin elevated activity but not dose-dependently. Regression analyses demonstrated that senktide and DiMe-C7 were the most potent and efficacious of the peptides tested. The slopes of the senktide and DiMe-C7 dose-response curves were parallel and differed significantly from the slope of the NKA dose-response curve. Infusions of the endogenous NK-3 ligand, NKB (3.0 pmol in 1.0 microliter), also elicited hyperactivity equivalent to that produced by an equimolar dose of senktide. These and previous findings suggest that activation of NK-2 and NK-3 receptors in the midbrain raphe leads to behavioral arousal through their influence on serotonin neurons.
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PMID:A dose-response analysis of intra-raphe tachykinin-induced hyperactivity. 279 67

The binding of tachykinin peptides and fragments to NK-2 receptor sites in hamster urinary bladder membranes was examined and compared to binding to NK-1 receptor sites in rat submandibular gland. Neurokinin A (NKA) and its C-terminal fragments bound with highest NK-2 affinity and selectivity. N-terminal fragments of NKA did not bind to either type of receptor. Kassinin and eledoisin were NK-2 selective while physalaemin, phyllomedusin, and uperolein were NK-1 selective. Of fifteen tachykinin antagonists examined, none exhibited appreciable affinity or selectivity (relative to agonists) for NK-1, NK-2, or rat cerebral cortical NK-3 receptor sites. NKA binding to NK-2 sites was stimulated by Mn++ greater than Mg++ greater than Ca++. At the optimal concentration, the Mn++ stimulation was due to both an increased Bmax and increased affinity. The nonhydrolyzable guanine nucleotide, GppNHp, reduced agonist binding but not antagonist binding to NK-2 receptor sites. The nucleotide effect was due to a reduction in both Bmax and affinity and was potentiated by Mn++. The results indicate that tachykinin NK-2 receptor sites possess distinct structural requirements for agonists and are linked to a G-protein coupling system.
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PMID:Agonist and antagonist binding to tachykinin peptide NK-2 receptors. 283 13


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