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)

Three tachykinin receptor types, termed NK1, NK2, and NK3, can be distinguished by the relative potency of various peptides in eliciting tissue responses. Airway macromolecular secretion is stimulated by the tachykinin substance P (SP). The purposes of this study were to determine the tachykinin receptor subtype responsible for this stimulation, and to examine the possible involvement of other neurotransmitters in mediating this effect. Ferret tracheal explants maintained in organ culture were labeled with 3H-glucosamine, a precursor of high molecular weight glycoconjugates (HMWG) which are released by airway secretory cells. Secretion of labeled HMWG then was determined in the absence and presence of the tachykinins SP, neurokinin A (NKA), neurokinin B (NKB), physalaemin (PHY), and eledoisin (ELE). All the tachykinins tested stimulated HMWG release to an approximately equal degree. Stimulation was concentration-related, with log concentrations giving half-maximal effects (EC50) as follows: SP -9.47, NKA -7.37, NKB -5.98, PHY -8.08, and ELE -7.68. This rank order of potency (SP greater than PHY greater than or equal to ELE greater than or equal to NKA greater than NKB) is most consistent with NK1 receptors. To evaluate the possible contribution of other mediators, tachykinin stimulation was examined in the presence of several receptor blockers. The potency of SP was not diminished by pretreatment with atropine, propranolol, or chlorpheniramine, and atropine actually increased the magnitude of the secretory response. The SP receptor antagonist [D-Arg1,D-Phe5, D-Trp7,9, Leu11]-SP blocked SP-induced secretion. These findings indicate that SP is a potent stimulus of airway macromolecular secretion. This effect occurs through the action of NK1 receptors, and is not dependent upon cholinergic, beta-adrenergic, or H-1 histamine receptors. The facilitation by atropine of SP stimulation suggests the existence of a mechanism of cholinergic inhibition of SP-induced stimulation.
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PMID:Tachykinin receptors mediating airway macromolecular secretion. 170 71

Pretreatment with capsaicin caused a depletion of substance P (SP)-, neurokinin A (NKA)- and calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) from the trigeminal ganglion, dura mater and cerebral arteries. The effect of capsaicin on isolated basilar arteries of guinea pig resulted in a biphasic relaxant response of histamine precontracted vessels. The first phase of the capsaicin-induced relaxation was absent in capsaicin-treated guinea pigs. Furthermore, repeated administration of capsaicin decreased the first but not the second phase of relaxation, supporting the view that a stored agent was released, while the second phase probably was due to a direct effect of capsaicin per se. The biphasic effect was not modified by the SP antagonist Spantide in a concentration that blocks tachykinin response (3.10(-6) M), nor by removal of the endothelium. There was no significant difference in pD2 values (-log concentration eliciting half maximum relaxation) between relaxations induced by SP, NKA, neurokinin B, neuropeptide K or CGRP in capsaicin pretreated as compared to vehicle-treated animals. These results are in support of the assumption that CGRP is involved in the capsaicin-induced relaxation caused by release of vasoactive agents from sensory afferent nerves.
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PMID:Evidence that calcitonin gene-related peptide contributes to the capsaicin-induced relaxation of guinea pig cerebral arteries. 170 99

The chemical features, pharmacological and biochemical characteristics of novel mammalian tachykinin peptides, neurokinin A and neurokinin B are described and are compared with those of substance P, a representative of tachykinin family.
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PMID:Neurokinin A and B. 170 77

Neurokinin A, neurokinin B and substance P caused concentration-related contractions of rabbit isolated aorta with pD2 values of 8.1, 6.9, and 6.0, respectively. [D-Pro2, D-Trp7, 9]-substance P, a competitive tachykinin antagonist, had pA2 values of 5.3 against neurokinin A, 5.1 against neurokinin B and 5.2 against substance P indicating that tachykinin receptors mediated responses to the agonists. [pGlu5,MePhe8,-MeGly9]-substance P 5 - 11 (DiMe-C7), senktide and septide did not contract the aorta. It is concluded that of the known tachykinin receptors smooth muscle of the rabbit isolated aorta contains only the NK-2 type.
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PMID:Smooth muscle of rabbit isolated aorta contains the NK-2 tachykinin receptor. 171 Jul 87

The vasomotor responses of tachykinins have been studied in the cerebral vasculature of human, pig, cat, and guinea pig. Substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and neuropeptide K (NPK) induced concentration-dependent relaxations of precontracted cerebral arteries in all species when examined by a sensitive in vitro technique. In addition, the relaxant responses to SP, NKA, and NKB were studied in cat pial arterioles by peptide microapplication in situ. In human pial vessels, the order of relaxant potency was SP greater than NKB greater than NKA greater than NPK; in the pig middle cerebral artery, there was no difference in potency between the tachykinins; in the cat middle cerebral artery, SP = NKB greater than NKA = NPK; and in the guinea pig basilar artery, SP much greater than NPK = NKA greater than NKB. Responses induced by SP, NKA, and NKB in the cat were comparable in vitro and in situ. Removal of the endothelium abolished relaxation induced by all four tachykinins. The relaxant responses of guinea pig basilar arteries to SP, NKA, and NPK were competitively antagonized by the SP antagonist Spantide. However, Spantide lowered the Imax of the NKB concentration-response curve without any rightward shift, suggesting action at a different site than the other tachykinins. In the guinea pig basilar artery, the relaxation seems to be exerted via a NK-1 receptor subtype while the receptor subtype is more unclear in cerebral arteries from human, cat, and pig.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tachykinins (substance P, neurokinin A, neuropeptide K, and neurokinin B) in the cerebral circulation: vasomotor responses in vitro and in situ. 171 Oct 51

1. Experiments were performed on anaesthetized, open-chest dogs to determine reflex effects on blood pressure and heart rate produced by stimulation of neural afferents of the left ventricular epicardium by local application of capsaicin, bradykinin, nicotine and the neuropeptides substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and calcitonin gene-related peptide (CGRP). 2. Studies also included assessing whether reflexogenic actions of capsaicin, bradykinin and nicotine are influenced by epicardial treatment with either neuropeptides, Ruthenium Red or neuraminidase. 3. Epicardial application of either capsaicin (0.1-10 micrograms) or bradykinin (0.1-1 micrograms), consistently resulted in dose-related increases in blood pressure and heart rate, whereas reflex bradycardia and hypotensive effects were initiated by the application of nicotine (30-50 micrograms). 4. SP, NKA, NKB and CGRP caused marked hypotensive effects and tachycardia when injected intravenously (1 microgram), but failed to produce any cardiovascular response when applied to the epicardium of the left ventricle (0.1-1 microgram). Treatment of the heart surface with these neuropeptides (0.05-0.5 micrograms min-1) was also without any effect on the magnitude of reflex responses evoked by epicardial application of either capsaicin, bradykinin or nicotine. 5. Superfusion of the ventricular epicardium with Ruthenium Red (10-30 microM), a cationic dye known to have sialic acid as a molecular target, antagonized the reflexogenic effects of capsaicin but not those of bradykinin or nicotine. The reflex effects of capsaicin, but not those of bradykinin, were also sensitive to inhibition by epicardial treatment with neuraminidase, an enzyme which cleaves sialic acid residues from glycosides and sialoglycoproteins. 6. We conclude that neuropeptides which may be released from the peripheral endings of some cardiac sensory neurons neither directly activate nor sensitize spinal sympathetic and vagal afferents in the dog heart to the reflexogenic action of bradykinin, nicotine or capsaicin. 7. We further suggest that activation of the cardiac sympathetic chemoreflex by capsaicin involves its interaction with calcium-binding sialic acid moieties present on the surface of axons and/or terminals of chemosensitive sympathetic afferents distributed in the dog ventricular epicardium.
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PMID:Effects of neuropeptides, ruthenium red and neuraminidase on chemoreflexes mediated by afferents in the dog epicardium. 171 37

1. We studied the effect of capsaicin and sensory neuropeptides on tracheal goblet cell secretion in anaesthetized guinea-pigs using a semi-quantitative morphometric technique whereby the magnitude of discharge of stained intracellular mucus, expressed as a mucus score (MS), was related inversely to discharge. 2. Capsaicin (i.v.) induced goblet cell secretion: a decrease of 50% in MS below control (indicative of increased secretion) was maximal at 3.3 x 10(-9) mol/kg. 3. Capsaicin-induced secretion was unaffected either by prior vagus nerve section or by pre-treatment with atropine, propranolol and phentolamine which suggests that local axon reflexes with release of sensory neuropeptides are involved in the response. 4. Intravenous substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and calcitonin gene-related peptide (CGRP) produced dose-related increases in goblet cell secretion, with SP the most potent. Doses (mol/kg) causing a 50% decrease in MS from control were 3.5 x 10(-12) for SP; 72 x 10(-10) for NKA; 1.6 x 10(-9) for NKB; and 1.2 x 10(-8) for CGRP. The maximal increase in goblet cell secretion was 75% of control and occurred with SP at 10(-10) mol/kg. 5. SP-induced mucus discharge was not inhibited by atropine or the histamine receptor antagonists mepyramine or cimetidine. 6. We conclude that in guinea-pig trachea, goblet cell secretion is under the control of capsaicin-sensitive sensory nerves and release of neuropeptides from these nerves may induce mucus discharge via tachykinin receptors of the NK-1 subtype (indicated by an order of potency of SP greater than NKA greater than NKB).
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PMID:Capsaicin and sensory neuropeptide stimulation of goblet cell secretion in guinea-pig trachea. 171 47

1. Contractile responses and acetylcholine release evoked by nicotine in guinea-pig detrusor strips were determined by isotonic transducer and radioimmunoassay, respectively. Nicotine stimulated acetylcholine release and a contractile response in guinea-pig detrusor strips treated with the cholinesterase inhibitor, methanesulphonyl fluoride (MSF). Both actions evoked by nicotine were antagonized by the nicotinic receptor antagonist, hexamethonium but were insensitive to tetrodotoxin. 2. A sympathetic nerve blocker, guanethidine and a tachykinin antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP) partially inhibited the acetylcholine release evoked by nicotine to much the same degree. The inhibitory effects of guanethidine and rpwwL-SP on acetylcholine release were significantly greater than corresponding effects on the contraction evoked by nicotine. 3. In preparations treated with rpwwL-SP to block the tachykinin receptors, guanethidine had no effect on the response to nicotine. Conversely, after treatment with guanethidine to block release of a mediator from sympathetic nerve endings, nicotine-induced responses were not affected by rpwwL-SP. 4. Nicotine-induced contraction was reduced to 30% by the muscarinic cholinoceptor antagonist, atropine and completely abolished after desensitization of P2-purinoceptors with alpha,beta-methylene ATP in the presence of atropine. 5. A concentration-contractile response curve to neurokinin A (NKA) was shifted to the left after cholinesterase inhibition with MSF. Atropine abolished the facilitatory effect of MSF and partially inhibited contractions induced by NKA at 100 nM to 1 microM. The contractile responses to substance P methyl ester (SPOMe) and Tyr0-neurokinin B (Tyr0-NKB) were not influenced by MSF or atropine. 6. After desensitization of NK, tachykinin receptors with SPOMe or preincubation with senktide, the cholinergic component of the nicotine-induced contraction was the same as the control value (100%). 7. Our findings give further support to our previous results: nicotine stimulates acetylcholine release in a tetrodotoxin-resistant manner in guinea-pig bladder and acetylcholine release evoked by nicotine is increased by the coordinated action of sympathetic nerves and tachykinin(s). It is suggested that the tachykinin receptor subtype involved in acetylcholine release is NK,.
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PMID:Contrasting effects of tachykinins and guanethidine on the acetylcholine output stimulated by nicotine from guinea-pig bladder [corrected]. 171 27

1 Plasma extravasation in the rat knee joint was induced by intra-articular injection of neurokinins and specific neurokinin receptor agonists. 2 Pronounced plasma extravasation was produced by substance P (SP, 4-185 microM) and to a lesser extent by neurokinin-B (NKB, 83-413 microM), whereas neurokinin-A (NKA, 88-440 microM) and calcitonin gene-related peptide (CGRP, 26-130 microM) had no significant effect. 3 The specific neurokinin1 receptor agonist [Sar9, Met(O2)11]-substance P (NK1 agonist) in doses of 0.4-70 microM appeared to be more potent than SP in eliciting plasma extravasation. The neurokinin2 receptor agonist [Nle10]-neurokinin A4-10 (NK2 agonist) was not effective at 70 microM but produced a small and significant effect at 330 microM, whereas the neurokinin3 receptor agonist [MePhe7]-neurokinin B (NK3 agonist) was without effect at 40 microM or 400 microM. 4 Injections of SP or NKA into the synovial cavity of the rat knee were equally effective in producing marked plasma extravasation in remote sites such as the forelimb and hindlimb paws. 5 Co-administration experiments showed that the effects of SP were synergistic with NKA or the NK1 receptor agonist, but not with CGRP or the NK2 receptor agonist. 6 The rank order of potency was NK1 agonist greater than or equal to SP greater than NKB greater than NK2 agonist suggesting that NK1 receptors mediate plasma extravasation in the rat knee joint.
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PMID:Specific neurokinin receptors mediate plasma extravasation in the rat knee joint. 171 29

1. The effects of scyliorhinins I (SCY I) and II (SCY II) on longitudinal (LM) and circular muscle (CM) strips isolated from the carp intestinal bulb were investigated in vitro and compared with that of substance P (SP). 2. SP (0.3 nM-1 microM), SCY I (0.3-300 nM) and SCY II (0.3 nM-1 microM) caused transient concentration-dependent contractions of LM strips. The EC50 values for SP, SCY I and SCY II were 16 nM, 15 nM and 39 nM, respectively. Tetrodotoxin and atropine partly decreased the contractile responses to SP, neurokinin A and neurokinin B, but did not change those to SCY I and SCY II. Spantide, methysergide, pyrilamine and naloxone did not decrease the contractile responses to SP, SCY I and SCY II. SP-induced desensitization selectively decreased the responsiveness of LM strips to SCY I and SCY II, and in addition, SCY I- or SCY II-induced desensitization decreased that to SP, SCY I and SCY II. 3. SP, SCY I and SCY II (1 nM-1 microM) caused concentration-dependent contraction of CM strips. The time course of the contractile response of CM strips was different from that of LM strips. Neither tetrodotoxin, atropine, methysergide nor spantide decreased the contractile responses to these tachykinins. 4. These results indicate that SCY I and SCY II act directly on tachykinin receptors located on smooth muscle cells and thus cause the excitatory response in the carp intestinal bulb.
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PMID:Excitatory responses to scyliorhinins I and II in smooth muscle strips isolated from the carp intestinal bulb (Cyprinus carpio). 171 22


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