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)

In the rat eye, intracameral injections of substance P in doses of 10-30 pmol caused a maximal long-lasting miosis and a leakage of plasma proteins into the aqueous humor, indicating a breakdown of the blood-aqueous barrier. Neurokinin A seemed equipotent to SP, but calcitonin-gene-related peptide (CGRP) (17 pmol) caused neither miosis nor protein leakage into the aqueous humor. The same result was obtained when CGRP was administered intravenously. Intracameral injection of capsaicin caused only a transient miosis which could not be repeated with further injections, even though the pupillary sphincter was still able to react to exogenous SP. Antidromic electrical stimulation of the trigeminal nerve caused plasma extravasation in the skin and a breakdown of the blood-aqueous barrier with an increased protein content in the aqueous humor. The stimulation did not affect the pupil size. The results indicate that in rat eyes SP and NKA are miotics, but the amounts that can be released from sensory nerve endings are too small to cause persistent miosis. These peptides are more likely to play a role in the neurogenic breakdown of the blood-aqueous barrier. CGRP at the same dose affects neither the pupillary sphincter muscle nor the barrier.
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PMID:Responses to antidromic trigeminal nerve stimulation, substance P, NKA, CGRP and capsaicin in the rat eye. 244 47

The autoradiographic localization of [125I]Bolton-Hunter substance P (BHSP) was examined in slide-mounted sections of dog kidney and dog renal artery and vein. Biochemical characterization of the binding in sections of dog kidney, demonstrated that BHSP binds to a population of non-interacting sites with high affinity (KD = 0.11 +/- 0.02 nM, Bmax = 0.29 +/- 0.05 fmol/section). The binding was displaced by tachykinins in the order SP greater than NKA much greater than NKB, indicative of binding to NK-1 receptors. BHSP binding to dog kidney was localized over glomeruli and endothelium of intrarenal arteries. There was binding associated with the endothelium and adventitia of the renal artery but not the vein. Binding of BHSP to arcuate arteries and to the renal artery was dependent on the presence of an intact endothelium. No evidence was obtained for receptors associated with any renal tubules. These results suggest that in the dog, vasodilation, diuresis and natriuresis in response to SP may result from an action primarily on the vascular elements of the kidney.
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PMID:Autoradiographic localization and characterization of substance P binding in dog kidney. 244 48

Neurokinins are active stimulants of the human isolated urinary bladder. In a preliminary study, performed on bladders taken from four donors, we attempted the characterization of neurokinin receptors. It was shown that neurokinin A is more active than neurokinin B and substance P. Neurokinin receptors selective agonists were also tested and it was found that the most active compound was the NK-A selective agonist, [Nle10]NKA 4-10: A substance P antagonist was able to reduce the effect of neurokinin A but its affinity was rather low. This suggests that the receptor mediating the contraction of the human urinary bladder to neurokinins is of the NK-A (NK2) type. The action of neurokinins on the human urinary bladder appears to be a direct one and mediated by specific receptors different from those of other agents. On the contrary, kinins were found to be active through a new mechanism which was not influenced by either anti-B1 or anti-B2 receptor antagonists.
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PMID:Substance P and neurokinins as stimulants of the human isolated urinary bladder. 245 93

A fraction enriched in neuronal growth cones isolated from developing rat forebrain was shown to possess binding sites for the substance P analog, Bolton-Hunter substance P [( 125I]BHSP). Specific binding of this ligand reached an equilibrium after 10 min at 20 degrees C, and was reversible and temperature-dependent. Removal of extracellular Na+ did not block but rather augmented [125I]BHSP binding suggesting that the labeled analog was not transported into the growth cone fraction. Scatchard analysis of the binding indicated a single class of non-interacting binding sites in the growth cone fraction (Kd: 257 pM; Bmax: 56 fmol/mg protein). From competition studies using substance P and other tachykinins, their rank order of potency for inhibiting [125I]BHSP binding was SP greater than physalaemin much greater than eledoisin greater than kassinin greater than NKB greater than or equal to NKA. Such order is consistent with the presence of an SP receptor (Neurokinin-1) in the growth cone fraction. The N-terminal fragments of substance P, SP1-7 and SP1-11 free acids, and the C-terminal fragment, SP7-11, were devoid of affinity for the [125I]BHSP binding site. However SP6-11 and SP1-11 methyl esters showed more potency.
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PMID:An isolated growth cone-enriched fraction from developing rat brain has substance P binding sites. 245 47

In the small intestine of urethane-anesthetized rats, i.v. neurokinins (NKs) (0.043-14 nmol/kg) produce three distinct motor effects, e.g.: 1) a transient relaxation followed by 2) a phasic contraction and 3) a tonic contraction. The aim of this study was to characterize the nature of the receptor determining the transient relaxation and mechanisms involved. The transient relaxation was more evident in the distal than in the proximal duodenum or in the jejunum. The rank order of potency of NKs in producing relaxation was NKA greater than substance P greater than NKB. The heptapeptide NKA(4-10) was as potent as the decapeptide NKA in determining relaxation but less potent than NKA in producing phasic or tonic contraction. NKA (0.43 nmol/kg i.v.)-induced relaxation and tonic contraction were unaffected by [D-Pro2, D-Trp7.g]substance P, a compound which, in this tissue, acts as a NK-1 receptor antagonist. NKA (0.43 nmol/kg i.v.)-induced relaxation of the distal duodenum was unaffected by atropine, hexamethonium or adrenalectomy, reduced by phentolamine plus propranolol and abolished by guanethidine or acute (15 min before) removal of the celiac ganglion complex. These findings are consistent with the hypothesis that activation of a NK-2 receptor located on postganglionic sympathetic neurons in the prevertebral ganglia produces the intestinal relaxation in response to i.v. NKs.
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PMID:Neurokinins induce a relaxation of the rat duodenum "in vivo" by activating postganglionic sympathetic elements in prevertebral ganglia: involvement of an NK-2 type of neurokinin receptor. 245 94

We have demonstrated a high affinity specific binding of 125I-Bolton Hunter conjugate of substance P (125I-BHSP) to rat retina membranes. The binding was saturable and monophasic with a Kd of 0.2 nM and a Bmax of 290 fmol/mg protein. The rank order of potency of tachykinins and related analogues in inhibiting 125I-BHSP binding conformed to that of the NK-1 (identical to SP-P) tachykinin receptor, with SP greater than NKA greater than or equal to KAS greater than or equal to NKB and [Glp6, L-Pro9]SP(6-11) being 60 times more active than [Glp6, D-Pro9]SP(6-11). After neonatal monosodium glutamate (MSG) treatment, there was a marked reduction in the number but not binding affinity of 125I-BHSP binding sites in the retina. The same treatment had no effect on either the number or binding affinities of NK-1 sites in the salivary gland.
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PMID:Effects of neonatal monosodium glutamate treatment on substance P binding sites in the rat retina. 246 98

Recent evidence suggests that activation of airway C-fibers, besides causing afferent transmission, also causes release of transmitters from peripheral endings, probably via local axon reflexes, resulting in effects on vascular and bronchial smooth muscle, i.e., vasodilatation, increase in vascular permeability, and bronchoconstriction. In the present study, the release of tachykinins was investigated in the perfused guinea pig lung by various ways of neuronal activation. Substance-P-like immunoreactivity (SP-LI) and neurokinin-A-like immunoreactivity (NKA-LI) was determined by radioimmunoassay in the perfusates. A significantly increased outflow of both SP-LI and NKA-LI was observed during perfusion of the lung with high potassium concentration (60 mM), the C-fiber activator capsaicin (1 microM), bradykinin (1 microM), histamine (100 microM), or the nicotinic agonist dimethylphenyl piperazinium (DMPP) (32 microM). Release of both SP-LI and NKA-LI could also be achieved by electrical stimulation of vagal nerves. The percental increase varied from 80 to 1,000% depending on the kind of stimulus. The release of tachykinins by K+ or capsaicin was greatly reduced in calcium-free medium. Release by histamine was completely inhibited by 1 microM mepyramine, and release by DMPP was abolished by 20 microM hexamethonium. High performance liquid chromatography indicated that NKA-LI consisted of several cross-reacting substances, presumably other peptides of the tachykinin family. Among the isolated mammalian tachykinins, NKA was the most potent one to contract tracheal smooth muscle of guinea pigs in vitro, followed by neurokinin B and by SP. Both NKA and SP relaxed the guinea pig pulmonary artery with similar potency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of multiple tachykinins from capsaicin-sensitive sensory nerves in the lung by bradykinin, histamine, dimethylphenyl piperazinium, and vagal nerve stimulation. 246 73

Rats were implanted with cannulae in the median raphe nucleus (MR). 5,7-Dihydroxytryptamine (5,7-DHT) or vehicle was infused either directly through the MR cannula, or bilaterally into the medial forebrain bundle (MFB). The MR 5,7-DHT lesions completely blocked the hyperactivity elicited by injections into the MR of the neurokinin (NK) 3 agonists, DiMe-C7 and senktide, and the NK-2 agonist, neurokinin A. In contrast, the MFB 5,7-DHT lesions did not affect the locomotor hyperactivity produced by intra-MR administration of DiMe-C7 and senktide, but appeared to attenuate the effects of NKA. The data indicate that intra-raphe neurokinin-induced hyperactivity is mediated by 5-HT neurons, and that 5-HT projections to the forebrain may be involved in the behavioral activation induced by intra-raphe neurokinin A administration, but not that induced by intra-MR NK-3 agonists.
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PMID:Intra-raphe neurokinin-induced hyperactivity: effects of 5,7-dihydroxytryptamine lesions. 246 17

The effects of neurokinins (NK) and related peptides on the secretion of 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin, were measured. These peptides enhanced three- to five-fold the basal secretion rate with the following rank order of potency (based on threshold concentrations for a significant output): substance P (SP) greater than or equal to NKA greater than SP 4-11 greater than or equal to [pGlu6]SP 6-11 = SP 7-11.NKB and SP 1-9 were inactive. Ac[Arg6, Sar9, Met(O2)11]SP, a NK1 receptor selective agonist, was more potent than other selective agonists for the NK2 and NK3 receptor subtypes. These results suggest that the NK receptors, which mediate the release of prostacyclin from human endothelial cells, belong to the NK1 subtype.
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PMID:Prostacyclin release induced by neurokinins in cultured human endothelial cells. 246 30

Cutaneous flushing was provoked in seven patients with metastatic carcinoid tumours and the carcinoid syndrome by an intravenous injection of pentagastrin (0.6 micrograms.kg-1 body weight). The patients were studied before and 1 h after a subcutaneous injection of the long-acting somatostatin analogue octreotide 50 micrograms (Sandostatin). The severity of the carcinoid flush in all the patients was reduced by administration of the analogue. The rise in facial temperature was 1.3 (0.3) degree C before and 0.8 (0.2) degree C after octreotide. Six patients responded to pentagastrin with a rise in the circulating neurokinin A-like immunoreactivity (NKA-LI) and five patients with a rise in circulating substance P-like immunoreactivity (SP-LI). No cutaneous flushing or rise in tachykinin concentration was observed in healthy subjects (n = 6) after injection of pentagastrin. The rise in NKA-LI in the patients was decreased by 61 (14)% and the rise in SP-LI by 54 (13)% after octreotide. Although flushing still occurred, the tachykinin response in two patients was completely abolished. The data demonstrate that the release of tachykinins from carcinoid tumours during pentagastrin-induced flushing is subject to partial inhibition by octreotide. However, the occurrence of a flush in some patients in the absence of a detectable rise in circulating tachykinins indicates that the latter peptides cannot be the sole causative agent of the carcinoid flush.
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PMID:Effect of a long-acting somatostatin analogue (octreotide) on circulating tachykinins and the pentagastrin-induced carcinoid flush. 247 May 92


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