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)

The binding of a radiolabeled bombesin analogue to human small cell lung cancer (SCLC) cell lines was investigated. (125I-Tyr4)bombesin bound with high affinity (Kd = 0.5 nM) to a single class of sites (2,000/cell) using SCLC line NCI-H446. Binding was reversible, saturable and specific. The pharmacology of binding was investigated using NCI-H466 and SCLC line NCI-H345. Bombesin and structurally related peptides, such as gastrin releasing peptide (GRP), but not other peptides, such as substance P or vasopressin, inhibited high affinity (125I-Tyr4)BN binding activity. Finally, the putative receptor, a 78,000 dalton polypeptide, was identified by purifying radiolabeled cell lysates on bombesin or GRP affinity resins and then displaying the bound polypeptides on sodium dodecylsulfate polyacrylamide gels. Because SCLC both produces bombesin/GRP-like peptides and contains high affinity receptors for these peptides, they may function as important autocrine regulatory factors for human SCLC.
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PMID:High affinity receptors for bombesin/GRP-like peptides on human small cell lung cancer. 240 23

The undecapeptide substance P (SP) is contained in enterochromaffin cells and circulates in high concentrations in patients with carcinoid syndrome. We have previously reported that elevated SP levels, simulating those reported in patients with carcinoid syndrome, induce profound changes in intestinal water and electrolyte secretion, motility, and blood flow in a canine model. The purpose of this study was to attempt to block the effects of circulating carcinoid levels of SP on intestinal secretion and motility with the calcium channel blocker verapamil. In five dogs a chronic proximal jejunal Thiry-Vella loop was constructed, and after a 2-week recovery the loops were perfused with an isotonic test solution containing 14C-polyethylene glycol as a volume marker. Motor activity was measured by changes in intraluminal pressure and a motility index was calculated with computer-assisted planimetry and expressed as square millimeters per 5 minutes. After a 30-minute baseline period, SP was infused at 50 ng/kg/min for 90 minutes. SP circulating levels rose from a baseline of 6.2 +/- 1.3 pg/ml to a peak of 93.3 +/- 3.1 pg/ml during this infusion. Thirty minutes after the start of this SP infusion, a simultaneous infusion of verapamil (5.0 micrograms/kg/min) was begun at a separate site. During SP infusion there was a significant secretory response of water (-48 +/- 12 microliters/min), Na+ (-7.7 +/- 2.5 microEq/min), Cl- (-8.8 +/- 2.7 microEq/min) and K+ (-0.57 +/- 0.14 microEq/min), and hypermotility (motility index: 1479 +/- 138 mm2/5 min). When verapamil was added a reversal of secretion to net absorption was observed (water: + 116.9 +/- 15.6 microliter/min; Na+: + 13.8 +/- 2.1 microEq/min; Cl-: + 5.5 +/- 2 microEq/min; K+: + 0.38 +/- 0.9 microEq/min) (p less than 0.05). In addition, there was a reduction in motility (motility index: 853 +/- 92 mm2/5 min; p less than 0.05). These results confirm that SP has profound effects on both intestinal motility and secretion and that calcium channel blockade reduces these effects significantly.
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PMID:Verapamil inhibition of the intestinal effects of substance P. 241 Sep 86

Nicotine-induced contraction of the isolated guinea pig bronchial preparation was abolished by capsaicin and a substance P (SP) antagonist [( D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP). Nicotine increased the release of immunoreactive SP from the preparations. The nicotine-evoked release of immunoreactive SP from the bronchial preparation was reduced by hexamethonium but not by tetrodotoxin. The results indicate that the responses to nicotine of the guinea pig bronchial preparation were mediated through the release of SP-like material(s), and that the nicotine-induced response may be produced through a process independent of the sodium action potential. In conclusion, the most likely site of action of nicotine in the isolated guinea pig bronchial preparation is the nicotinic receptor of SP immunoreactive nerves.
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PMID:Possible involvement of substance P immunoreactive nerves in the mediation of nicotine-induced contractile responses in isolated guinea pig bronchus. 241 45

The binding of [3H]substance P (SP) to membranes of the rat small intestine demonstrates specific binding to receptors having more than one affinity for SP. The values of the binding parameters for the high-affinity site obtained from a non-linear regression analysis are as follows: KD = 0.25 nM, Bmax = 149.5 fmol/mg protein. Inhibition curves of 3H-SP binding using various unlabeled tachykinins show that the high-affinity receptor is of the P-subtype, having the highest affinity for SP and lower affinities for eledoisin and kassinin. Guanine nucleotides and sodium independently reduce the binding of 3H-SP to the high-affinity receptor in a dose-related manner; GTP and GDP are more potent than GMP. The reduction of specific SP binding by GTP can be ascribed primarily to an increase in the off-rate. The effects of guanine nucleotides on 3H-SP binding to membranes of rat small intestine suggest that the high-affinity receptor is linked to an effector by a GTP-binding regulatory protein.
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PMID:Guanine nucleotides regulate [3H]substance P binding in rat small intestine. 241 4

Substance P is a peptide implicated in the control of a variety of physiological processes. Although substance P-containing neurons impinge on the pulmonary vasculature, the effects of substance P on the pulmonary circulation have not been systematically investigated. Rabbits were anesthetized with methohexital sodium and paralyzed with pancuronium bromide. Injection of substance P (0.002-0.10 microgram/kg) in the vena cava produced dose-dependent pulmonary vasoconstriction and systemic vasodilation. Pulmonary arterial pressure reached a peak within 15-20 s and declined toward base line over 10 min. Aortic pressure fell rapidly, reaching minimum at 5-10 s. At higher doses cardiac output fell transiently, resulting in a 65% fall in pulmonary vascular conductance. If repeat substance P dosages were administered 15 min apart, there was no tachyphylaxis. Pulmonary vasoconstriction was inhibited by the cyclooxygenase blocker meclofenamate (10 mg/kg) and the thromboxane synthase inhibitor Dazmegrel (UK-38,485) (2 mg/kg). In contrast, vasoconstriction was enhanced by atropine (2 mg/kg). In Dazmegrel-treated animals in whom pulmonary vasoconstriction was established by epinephrine infusion, low doses of substance P produced vasodilation. Our findings indicate that substance P produces pulmonary vasoconstriction via prostaglandin (particularly thromboxane) generation and pulmonary vasodilation via activation of cholinergic pathways.
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PMID:Opposing hemodynamic effects of substance P on pulmonary vasculature in rabbits. 241 67

Substance P is known to modulate acetylcholine-induced catecholamine release from adrenal chromaffin cells. To investigate the mechanisms involved in this modulation, the present study examined the effects of substance P on net 45Ca2+ fluxes in cultures of bovine adrenal chromaffin cells. Two effects of substance P were observed: (1) Substance P inhibited carbachol-induced 45Ca2+ uptake and 45Ca2+ efflux and (2) substance P protected against desensitization of carbachol-induced 45Ca2+ uptake and 45Ca2+ efflux. Thus substance P modulates two other cholinergic responses, 45Ca2+ uptake and 45Ca2+ efflux, in a manner similar to its modulation of catecholamine release. The results also indicate that substance P's inhibition of net carbachol-induced 45Ca2+ uptake is due to inhibition of 45Ca2+ uptake rather than enhancement of 45Ca2+ efflux. Substance P almost completely inhibited carbachol-induced 45Ca2+ uptake in both Na+-containing and Na+-free media, suggesting that substance P can inhibit the uptake of 45Ca2+ induced by carbachol regardless of whether 45Ca2+ is taken up through voltage-sensitive or acetylcholine receptor-linked channels. However, substance P produced only a small inhibition of K+-induced 45Ca2+ uptake, indicating that substance P does not interact directly with voltage-sensitive Ca2+ channels. In addition, substance P's inhibition of carbachol-induced 45Ca2+ uptake was noncompetitive with respect to Ca2+, were unable to overcome substance P's inhibition of [3H]-norepinephrine ( [3H]NE) release. It is concluded that substance P does not interact directly with Ca2+ channels in bovine adrenal chromaffin cells.
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PMID:Effects of substance P on carbachol-stimulated 45Ca2+ uptake into cultured adrenal chromaffin cells. 241 2

The three-dimensional structure of substance P has been studied by 1H-NMR, (500 MHz), and by circular dichroism (CD) in different solvents. The analysis of the different NMR parameters suggest that substance P adopts a rather extended structure in dimethylsulfoxide and pyridine. In water, besides the aggregation phenomenon, the monomeric substance P presents a complex conformational equilibrium. The addition of sodium dodecylsulfate to the aqueous solution induces, as shown by CD spectroscopy, a preferential alpha-helical conformation. And in methanol three structural conclusions may be drawn: the flexibility of the N-terminal Arg-Pro-Lys, the alpha-helical structure of Pro4-Gln5-Gln6-Phe7-Phe8 and the interaction of the C-terminal carboxamide with the primary amides from both glutamines.
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PMID:Preferential conformation of substance P in solution. 241 37

This study was initiated to evaluate the effect of luminally administered serotonin (5-hydroxytryptamine) and substance P on jejunal handling of water and electrolytes. Five dogs with chronic cannulated jejunal Thiry-Vella loops were studied. The isolated jejunal segments were perfused at 2 ml/min for 2 hours with an isosmotic, isothermic perfusate containing labeled polyethylene glycol for recovery calculation. Fluxes of water and sodium, chloride, and potassium were calculated during 30 minute baseline, 60 minute study, and 30 minute recovery periods. Substance P was administered intraluminally at 25 pg/ml, whereas serotonin was perfused at 600 ng/ml. Neither hormone was absorbed into the portal circulation. Intraluminal serotonin converted absorption to secretion of water from 43 +/- 23 to -105 +/- 25 microliters/min, sodium from 7.3 +/- 3.1 to -15.7 +/- 4.1 microEq/min, chloride from 4.4 +/- 3.4 to -16.4 +/- 3 microEq/min, and potassium from 0.16 +/- 0.20 to -0.86 +/- 0.17 microEq/min. Secretion ceased on cessation of serotonin perfusion. Substance P perfusion induced secretion of chloride (3.6 +/- 1.9 to -9.2 +/- 2.9 microEq/min) but only significantly decreased absorption of water (73 +/- 13 to 13 +/- 21 microliters/min) and sodium (8.1 +/- 1.9 to 0.2 +/- 3.1 microEq/min); in contrast, there was no significant change in jejunal handling of potassium.
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PMID:Effect of luminally administered serotonin and substance P on jejunal handling of water and electrolytes. 241 2

Adenosine and its derivatives enhanced the contractile responses to transmural nerve stimulation in rabbit isolated bronchial smooth muscle. 5'-N-Ethylcarboxamideadenosine (NECA) was the most potent adenosine analogue studied. Enhancement of contractile responses by NECA was competitively antagonized by 8-p-sulfophenyltheophylline. Guanethidine, mepyramine, capsaicin or eicosatetraynoic acid did not antagonize the enhancement elicited by adenosine or NECA. NECA did not enhance the contractile responses to exogenously applied acetylcholine or contractile responses elicited after administration of tetrodotoxin. We suggest that adenosine, via an action at A2 receptors, enhances contractile responses to nerve stimulation in rabbit bronchial muscle. Methylxanthines are competitive antagonists at these extracellular receptors. The enhancement probably involves a sodium-dependent mechanism but not adrenergic mechanisms or release of histamine, substance P or arachidonate metabolites. The enhancement indicates increased cholinergic transmitter release or action, but release of a secondary spasmogenic or decreased release of an inhibitor mediator cannot be excluded. The results may indicate a role for adenosine in asthma.
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PMID:Apparent enhancement of cholinergic transmission in rabbit bronchi via adenosine A2 receptors. 241 45

This study was initiated to determine if raised (carcinoid) plasma concentrations of substance P induced jejunal secretion of water and electrolytes. Five dogs had isolated and cannulated 25 cm jejunal segments perfused at 2 ml/min with a neutral, isotonic perfusate. Saline, 1.0 ml, was infused intravenously during basal and recovery periods, while substance P was administered intravenously at 75 ng/kg/min (55 pmol/kg/min) during the four 15 minute experimental periods. Infusion increased plasma SP concentrations from basal (5.8 +/- 1.3 pg/ml) to a mean plateau level of 121.2 +/- 25.2 pg/ml (mean +/- SEM). During SP infusion, intestinal secretion of water, Na+, and Cl- were documented (H2O basal +102 +/- 60 to SP -275 +/- 60; microliter/min; Na+ basal +19.8 +/- 7.2 to SP -23.2 +/- 7.5 microEq/min; Cl- basal 21.7 +/- 7.5 to SP -16.5 +/- 5.6 microEq/min). Under basal conditions, there was minimal secretion of potassium (-0.264 +/- 0.282 microEq/min); during SP infusion, K+ flux was altered to significant secretion (-1.784 +/- 0.271 microEq/min). Serum concentrations of Na and Cl were unchanged during SP infusion, but serum potassium concentrations fell from 4.64 +/- 0.12 to 3.85 +/- 0.40 mEq/l. The data demonstrate that substance P at levels noted in the carcinoid syndrome induces significant jejunal secretion of water and electrolytes in the dog.
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PMID:Substance P-induced intestinal secretion of water and electrolytes. 242 93


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