Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:035231 (NKB)
 244 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Muscularis mucosae of the distal oesophagus of the opossum contracts in response to substance P and to a variety of tachykinins. To delineate the nature of the receptors present in this tissue, we evaluated contractile responses to substance P, neurokinin A, neurokinin B, eledoisin and analogues believed to be highly selective for NK-1, NK-2 and NK-3 receptors. In addition, the effects of prolonged exposure to each of these agents (10(-6) M or 10(-5) M) on contractile responses to substance P and to itself were evaluated. Similarly effects of prolonged exposure to the various tachykinins and their analogues on the field-stimulated responses of this muscle were studied. 2. All naturally occurring tachykinins were full agonists and differed in potency (comparing ED50 values) by less than ten fold. In nearly all cases there was cross tachyphylaxis between substance P and the other tachykinins and each reduced tonic responses to field stimulation, a response previously shown to be mediated by a substance P like agent. Eledoisin failed to cause tachyphylaxis under the conditions of these experiments. 3. When highly selective tachykinin analogues were used, only that believed to activate NK-1 receptors was a full agonist. [beta-Ala4,Sar9,MetO2(11)]SP(4-11) was also only slightly less potent than substance P. In contrast, an agonist selective for NK-2 (NK-A) receptors, [Nle10]NKA(4-10), and one selective for NK-3 (NK-B) receptors, [beta-Asp4, MePhe7]NKB(4-10) were unable to produce a response equal to 50% of the maximum even at 10(-5) M. However, all three selective tachykinin analogues reduced responses to substance P but not to carbachol. They usually reduced both phasic and tonic responses to field stimulation. 4. We conclude, based on this and earlier study, that the tachykinin receptors of opossum oesophagus muscularis mucosae recognize all naturally occurring tachykinins but may represent only NK-1 receptors. The ability of analogues selective for other types of tachykinin receptors to reduce responses to substance P raises the possibility that their selectivity depends in part on diminished efficacy rather than totally on diminished affinity at some classes of receptor.
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PMID:Classification of tachykinin receptors in muscularis mucosae of opossum oesophagus. 247

Mammalian tachykinins (substance P, neurokinin A and neurokinin B) produced a concentration-related contraction of the hamster isolated trachea with the following order of potency: NKA congruent to NKB much greater than substance P (SP). NKA and NKB were 280 and 203 times more potent than SP, respectively. The action of NKA, NKB or SP was not significantly modified in presence of thiorphan (10 microM), atropine (1 microM), mepyramine (1 microM) or indomethacin (5 microM). [Nle10]NKA-(4-10) or [beta Ala8]NKA-(4-10), two selective NK-2 receptor agonists, displayed good activity while other synthetic agonists, selective for NK-1 or NK-3 receptors, had little or no effect. The contractile response to tachykinins did not undergo appreciable desensitization and was promptly reversed by washing out. These data indicate that NK-2 receptors are the main if not the sole mediators of the response of the hamster isolated trachea to tachykinins, whose action is independent from cholinergic nerves, histamine release or prostaglandin production. Further, no significant peptide degradation by a thiorphan-sensitive mechanism occurs in this organ.
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PMID:The hamster isolated trachea: a new preparation for studying NK-2 receptors. 247 73

An N-terminally directed antiserum to neurokinin B was raised in rabbits using an immunogen prepared by coupling the free-SH group of neurokinin B extended from its C-terminus by a cysteine residue (NKB-Cys) to an -NH2 group on human serum albumin using a heterobifunctional cross-linking reagent. In radioimmunoassay with 125I-Bolton-Hunter-labelled NKB-Cys as tracer, the antiserum showed no cross-reactivity with other tachykinins. An extract of a human pheochromocytoma, previously shown to contain peptides derived from preprotachykinin A, contained NKB-LI (13 pmol/g wet weight). The retention time of tumor neurokinin on reversed-phase HPLC was the same as that of synthetic neurokinin B. Peptides with the retention times of substance P, neurokinin A, neurokinin A (3-10)-peptide and neuropeptide K were also identified in the tumor extract. NKB-LI was not detected in extracts of a further nine pheochromocytomas or in five carcinoid tumors that expressed the preprotachykinin A gene.
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PMID:Neurokinin B in a human pheochromocytoma measured with a specific radioimmunoassay. 278 Apr 25

A novel and highly specific radioimmunoassay for the tachykinin peptide neuromedin K (NMK, also known as neurokinin beta, neurokinin B) has been developed and used to determine the distribution of this peptide in extracts of guinea pig tissues. In addition to immunoreactive components coeluting with the 3 mammalian tachykinins, substance P (SP), substance K (SK) and NMK, analyses using reverse-phase HPLC revealed immunoreactive peaks coeluting with the C-terminal octapeptide of SK (SK-(3-10], an N-terminally extended form of SK (gamma-preprotachykinin-(72-92)amide), and a yet unidentified peak eluting before NMK in the extracts of guinea pig brain and spinal cord. In contrast to the other tachykinins, SP and SK, which were present in high concentrations in extracts of all peripheral and central tissues examined, NMK-like immunoreactivity was detected only in extracts of central tissues. NMK-like immunoreactivity was not detected in extracts of terminal ileum and urinary bladder.
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PMID:A novel radioimmunoassay for neuromedin K. I. Absence of neuromedin K-like immunoreactivity in guinea pig ileum and urinary bladder. II. Heterogeneity of tachykinins in guinea pig tissues. 279 56

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

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 distribution of neurokinin receptors in rat kidney, renal artery, renal vein, and proximal ureter was evaluated by autoradiography after in vitro labeling of NK1 sites with [125I]Bolton-Hunter substance P (BHSP) or NK3 sites with [125I][MePhe7]neurokinin B ([MePhe7]NKB). Film autoradiography using [125I][MePhe7]NKB revealed specific binding sites associated with the renal vein and its large branches, the renal pelvis, the inner strip of outer renal medulla, and the proximal ureter. High-resolution autoradiograms demonstrated that these sites were localized to the smooth muscle layer in the veins, pelvis, and ureter. Neither the renal arterial system nor the renal cortex contained specific [125I][MePhe7]NKB binding sites although a high level of nonspecific binding was associated with the renal artery. Specific binding of [125I]BHSP was associated with the renal artery and renal pelvis but not the renal veins. Arterial NK1 receptors appeared to be localized to the adventitia. The results indicate that at least two types of tachykinin receptor are present in the rat kidney. The distinct localization observed for most of the NK1 and NK3 receptors suggests that they have different functions.
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PMID:Autoradiographic localization of NK1 and NK3 tachykinin receptors in rat kidney. 747 2

Using intracellular current clamp recording from motoneurones of the neonatal rat spinal cord in vitro, the action of tachykinin receptor agonists was investigated. Test drugs included the endogenously occurring neuropeptide substance P and synthetic compounds, such as substance P methylester (SPMeO), [beta Ala8]neurokinin A4-10 ([Ala]NKA), [MePhe7]neurokinin B ([MePhe]NKB) and senktide. SPMeO and [Ala]NKA were used as selective agonists at NK1 and NK2 receptors, respectively, while [MePhe]NKB or senktide were employed to activate NK3 receptors. In control solution, all compounds produced sustained depolarization with increase in input resistance although at comparable levels of membrane depolarization different patterns of motoneuronal firing were observed dependent on the type of agonist tested. In tetrodotoxin (TTX; 1 microM) solution, the depolarization caused by substance P or SPMeO largely persisted while in the majority of cells the effect of [Ala]NKA, [MePhe]NKB or senktide was blocked. It is suggested that NK1 receptors primarily mediated the actions of substance P on spinal motoneurones and that activation of NK2 or NK3 receptors, predominantly found on interneurones, induced motoneuronal depolarization with different firing patterns.
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PMID:Multiple types of tachykinin receptor mediate a slow excitation of rat spinal motoneurones in vitro. 751 26

1. The effects of intracerebroventricular (i.c.v.) injection of selective and potent NK1 (RP 67580), NK2 (SR 48968) and NK3 (R 486, [Trp7, beta-Ala8]NKA(4-10)) receptor antagonists were assessed on the cardiovascular and behavioural responses elicited by the i.c.v. injection of substance P (SP), neurokinin A (NKA) or [MePhe7]neurokinin B ([MePhe7]NKB) in the conscious freely moving rat. 2. SP, NKA and [MePhe7]NKB (5-650 pmol) evoked dose-dependent increases in mean arterial blood pressure (MAP) and heart rate (HR) with the rank order of potency SP > NKA > [MePhe7]NKB. The cardiovascular responses were accompanied by excessive face washing, grooming and wet dog shakes. 3. The cardiovascular effects and face washing behaviour induced by SP (25 pmol) were significantly reduced by the pre-injection (i.c.v., 5 min earlier) of RP 67580 (6.5 nmol). However, this antagonist failed to affect the central effects of 25 pmol NKA or [MePhe7]NKB. 4. The cardiovascular and behavioural responses (except for wet dog shakes) elicited by NKA (25 pmol) were significantly reduced by 6.5 nmol SR 48968. However, the latter antagonist had no effect on the SP or [MePhe7]NKB-mediated responses. 5. Both cardiovascular and behavioural effects produced by either SP or NKA (25 pmol) were completely abolished when rats were pretreated with a combination of RP 67580 (6.5 nmol) and SR 48968 (6.5 nmol), yet this combination of antagonists failed to modify the central effects of [MePhe7]NKB. 6. R 486 (6.5 nmol) inhibited the cardiovascular effects as well as wet dog shakes produced by [MePhe7]NKB, but it was inactive against the responses induced by either SP or NKA. 7. None of the tachykinin receptor antagonists or agonists caused motor impairment or respiratory distress. All antagonists blocked in a reversible manner and were devoid of intrinsic activity except R486 (6.5 nmol) which produced a transient increase of MAP and HR.8. These results suggest that the central effects of SP, NKA and [MePhe7]NKB are primarily mediated by central NK1, NK2 and NK3 receptors, respectively. However, a minor activation of NK2 receptors bySP and NK1 receptors by NKA was seen during blockade of both receptors. This study therefore supports the existence of functional NK1, NK2 and NK3 receptors in the adult rat brain.
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PMID:Cardiovascular and behavioural effects of centrally administered tachykinins in the rat: characterization of receptors with selective antagonists. 751 4

Actions of substance P (SP, 10(-9) to 10(-6) M), neurokinin A (NKA, 10(-9) to 10(-6) M) and neurokinin B (NKB, 10(-10) to 10(-6) M) in the circular muscle of guinea pig ileum were investigated in segment and strip preparations, in which methacholine produced similar contractions. In the segment preparations, three tachykinins produced repeatedly occurring twitch-like contractions. Their efficacies were similar with the same maximal contractions, but their potencies were different (NKB > NKA = SP). Latency (38 sec) was observed before the initiation of contractions in response to NKA, but not to SP or NKB. Atropine (10(-6) M) and tetrodotoxin (3 x 10(-7) M) did not affect NKA-induced contractions, but inhibited SP- and NKB-induced contractions; the dose-response curves for SP and NKB were rightwardly shifted by atropine. The treatment with atropine brought out latency in the responses for NKB. In the strip preparations, SP did not substantially induce concentrations, but NKA and NKB produced twitch-like contractions after latent periods of 28 and 36 sec, respectively. The efficacy of NKA was similar to that in segment preparations, while that of NKB was much lower in strip preparations. Unlike in segment preparations, atropine did not inhibit contractions induced by the two tachykinins in strip preparations. These results suggest that tachykinins induce contractions through myogenic and neurogenic mechanisms, the latter of which may be inoperative in strip preparations.
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PMID:Tachykinin-induced contractions in the circular muscle of guinea pig ileum. 752 85


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