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)

Neurokinin A (NKA) and B (NKB) were more potent bronchoconstrictive agents than substance P (SP) in guinea pig tracheal strips. The content of NKA in guinea pig lung homogenate was 2.26 +/- 1.09 pmol/g wet lung, which was approximately half that of SP (4.46 +/- 1.33 pmol/g wet lung); NKB was not detected in the guinea pig lung homogenate (less than 0.01 pmol/g wet lung). Histologically, NKA-immunoreactive fibers were distributed in the bronchial smooth muscle layers. Pulmonary arteries and veins were also found to be innervated by NKA-immunoreactive nerves. In addition, a few fibers were observed in the trachea, bronchioles, and alveoli. These findings suggest that NKA may be one of the neurotransmitters of the noncholinergic bronchoconstrictive nerves.
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PMID:Neurokinin A as a potent bronchoconstrictor. 282 Feb 82

The three mammalian neurokinins, substance P, neurokinin A and neurokinin B, as well as some agonists selective for their respective receptors, NK-P, NK-A and NK-B, were tested in a variety of pharmacological preparations in order to evaluate if the biological responses of the various tissues were mediated by single or multiple receptor types. Previous observations that the dog carotid artery, the rabbit pulmonary artery and the rat portal vein are selective preparations respectively for SP, NKA and NKB were confirmed in the present study by showing that only the respective selective agonists were active on these tissues. Multiple functional sites were demonstrated in intestinal tissues (guinea pig ileum, rat duodenum), which apparently contain the three neurokinin receptors. A large number of NK-P, together with some NK-A receptor sites were found in the guinea pig and rat urinary bladder. Similarly, the guinea pig trachea and the rabbit mesenteric vein contain NK-A and NK-P functional sites. Rat and rabbit vas deferens stimulated electrically respond as typical NK-A preparations, since they are almost insensitive to SP or NKB selective agonists. A mixture of NK-A and NK-B receptor sites has been shown to be present in the hamster urinary bladder: dog and human urinary bladder definitely contain NK-A receptors and the dog bladder also some NK-P functional sites.
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PMID:Characterization of neurokinin receptors in various isolated organs by the use of selective agonists. 282 47

3H-Neurokinin A (3H-NKA) with high specific activity (75 Ci/mmol) was synthesized to study NKA (NK-2)-binding sites on membrane preparations of various tissues in the rat, including brain, spinal cord, duodenum, vas deferens, and ileum. The binding capacity of 3H-NKA (0.9 nM) was very low in membrane preparations of different central nervous system regions and the ileum smooth muscle (0.2-2 fmol/mg of protein). In contrast, relatively high specific binding was found in membrane suspensions of the rat duodenal smooth muscle (18 fmol/mg of protein) and the vas deferens (8 fmol/mg of protein). 3H-NKA-binding sites were further characterized on the rat duodenal smooth muscle. The specific binding of 3H-NKA was shown to be temperature dependent, saturable, reversible, and increased in parallel with the protein concentration. Scatchard analyses and Hill plots of equilibrium binding studies in the concentration range of 0.40-30 nM revealed that 3H-NKA bound to a single class of noninteracting binding sites (Bmax = 270 fmol/mg of protein, KD = 13.3 nM). Displacement of 3H-NKA with different tachykinin-related peptides gave the following rank order of potencies: NKA greater than NKA (4-10) greater than kassinin greater than eledoisin greater than NKB much greater than substance P greater than physalaemin, which suggests that the binding site labeled by 3H-NKA is different from substance P (NK-1)-and NKB (NK-3)-binding sites. The biological activities of tachykinins and related peptides were tested by measuring their contractile effects on the rat duodenum and rabbit pulmonary artery, two tissues known to be sensitive for NKA. Ki values were correlated with the EC50 obtained in biological assays. The results revealed a significant correlation (r = 0.86, p less than 0.01) between Ki and EC50 values obtained in the isolated rabbit pulmonary artery, whereas there was no significant correlation between binding affinities and biological responses on the rat duodenum (r = 0.62, p greater than 0.05).
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PMID:3H-neurokinin A labels a specific tachykinin-binding site in the rat duodenal smooth muscle. 282 90

A comparative autoradiographic analysis of the distribution of tachykinin binding sites was made on brain serial sections using several ligands. (1) 3H-SP, 125I-BHSP and 3H-physalaemin labeled identical binding sites (NK1 type). (2) 3H-NKB, 125I-BHE and 3H-eledoisin also labeled identical sites (NK3 type). (3) 125I-BHNKA preferentially labeled NK3 binding sites, the distribution of 125I-BHNKA binding sites being identical to that of 3H-NKB or 125I-BHE binding sites. (4) The distributions of 3H-SP and 3H-NKB binding sites were markedly different. (5) A very low density of labeling was found with 3H-NKA or 125I-NKA, and these binding sites were distributed only in areas rich in either 3H-SP or 3H-NKB binding sites. (6) Particular efforts were made to look for the presence of tachykinin binding sites in the substantia nigra, since this structure is particularly rich in SP and NKA and contains functional tachykinin receptors of the NK1 and NK2 types as suggested by physiological studies. Confirming previous reports, low or very low labeling was observed in the substantia nigra with 3H-SP or 125I-BHSP and 3H-NKB or 125I-BHE. Similar results were found with 3H-NKA, 125I-NKA or 125I-BHNKA. In conclusion, our data do not provide evidence yet for the existence of NK2 binding sites in the rat brain.
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PMID:Localization of tachykinin binding sites (NK1, NK2, NK3 ligands) in the rat brain. 283 23

A phosphoinositide-linked peptide response in cultured rat astrocytes was studied by measuring the accumulation of [3H]inositol phosphates in the presence of lithium. Cultures derived from cortex, cerebellum and spinal cord each showed a unique pattern or degree of stimulation to a panel of neuropeptides. Cortical and cerebellar astrocytes were similar, responding to bradykinin, oxytocin, vasopressin, eledoisin and neurokinin beta, whereas spinal cord astrocytes were stimulated by substance P, bradykinin, eledoisin, and neurokinins alpha and beta. These observations are evidence in favour of regional specialisations of astrocytes which may respond uniquely to peptides released by particular populations of neurons.
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PMID:A phosphoinositide-linked peptide response in astrocytes: evidence for regional heterogeneity. 283 90

Complications of the gastrointestinal tract in patients with diabetes mellitus can cause marked discomfort and may modify the ability of the patient to maintain normal glucostasis. In an attempt to elucidate some of the factors causing gastrointestinal dysfunction in experimental diabetes we examined the responses of jejunal smooth muscle in streptozotocin-induced diabetes in rats to some of the neurotransmitters and autocoids found in the enteric nervous system. Jejunal tissues from 4- to 5-week diabetic rats were examined for their responses to neurokinin (NK) A, NKB, substance P (SP), bradykinin, neurotensin, bethanechol, isoproterenol and phenylephrine. The affinities for all these agonists, except for SP which increased slightly with diabetes, were the same in both control and diabetic tissues. NKA was the most potent neurokinin and elicited the largest contractile responses from jejunal tissues of both control and diabetic animals. The contractile response to NKA, but not that to NKB or SP, was increased in the jejunum from diabetic animals. Part of this increased responsiveness was antagonized by atropine. The contractile effects of the cholinergic agonist, bethanechol, were not altered by the diabetic state. Decreased relaxation responses in the jejunum from diabetic animals were observed for bradykinin, neurotensin and isoproterenol, but not for phenylephrine. These results suggest that the myogenic actions of several agonists are modified in experimental diabetes.
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PMID:Modified smooth muscle responses of jejunum in streptozotocin-diabetic rats. 290 44

[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

A series of analogues of the partial sequence NKB-(4-10) (H-Asp-Phe-Phe-Val-Gly-Leu-Met.NH2) was prepared in an attempt to identify selective agonists for the neurokinin B receptor type. The compounds were tested in the dog carotid artery, the rabbit pulmonary artery and the rat portal vein to evaluate their affinity for the receptors of substance P, neurokinin A and neurokinin B respectively. It has been shown that the replacement of Val7 with MePhe increased significantly the affinity of NKB-(4-10) for the neurokinin B receptor and confered marked selectivity. [MePhe7]NKB-(4-10) was practically inactive as stimulant of the receptor for NKA and was a weak agonist on the receptor for SP. Such significant changes in the pharmacological spectrum of [MePhe7]NKB-(4-10) cannot be attributed to protection from metabolism and appear to be due to changes in the peptide conformation.
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PMID:Specific agonists for neurokinin B receptors. 303 72

The actions of two new mammalian tachykinins, neurokinin alpha and neurokinin beta, were examined using the isolated spinal cords of newborn rats. Depolarizing responses of spinal motoneurons were recorded extracellularly from the lumbar ventral root during application of neurokinin alpha or neurokinin beta at concentrations ranging from 3 X 10(-8) M to 10(-6) M. The potencies of various tachykinins in depolarizing the motoneurons showed the following order: physalaemin greater than neurokinin beta divided by kassinin divided by substance P greater than neurokinin alpha. When the synaptic transmission in the spinal cord was blocked by tetrodotoxin, the depolarizing action of neurokinin alpha and neurokinin beta was markedly reduced but not completely abolished. The depolarizing action of neurokinin alpha and neurokinin beta was depressed by a substance P antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP. The possibility that neurokinin alpha and neurokinin beta act as neurotransmitters in the mammalian spinal cord is discussed.
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PMID:The excitatory action of the newly-discovered mammalian tachykinins, neurokinin alpha and neurokinin beta, on neurons of the isolated spinal cord of the newborn rat. 608 49

Recently, we have found novel mammalian tachykinins, neurokinin alpha and beta isolated from porcine spinal cord, whose chemical structures are similar to those of substance P or kassinin. In the present study, we describe a specific assay system for neurokinin alpha and beta by combining HPLC and radioimmunoassay. We investigated the regional distribution of tachykinins including substance P in the rat central nervous system using anti-neurokinin alpha antiserum which cross-reacts 25% with neurokinin beta. As a result, it is noted that substance P was the highest in concentration in the rat substantia nigra, the striatum, the cerebellum and the spinal cord, but not in the cerebral cortex in which neurokinin beta was the highest. Concentration of neurokinin alpha was lower than that of substance P and the molar ratio of substance P and neurokinin alpha was fairly constant (2.8-4.0) in all regions. On the other hand, it is noted that the molar ratio of substance P and neurokinin beta was extremely variable and seemed to be specific to tissues.
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PMID:Regional distribution of substance P, neurokinin alpha and neurokinin beta in rat central nervous system. 608 50


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