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)

1. Whole-cell recording was used to investigate the effects of substance P on cultured neurones from the rat nucleus basalis. 2. Brief applications of substance P produced a reduction, about 1 min in duration, of resting membrane conductance. The concentration producing a half-maximal effect was approximately 40 nM, with the continuous presence of substance P resulting in desensitization of the response. 3. The control current-voltage relation exhibited inward rectification over the voltage range -70 to -150 mV, and hyperpolarization produced a time-dependent decrease of current (inactivation). 4. The substance P-sensitive current, obtained by subtracting the current during the presence of the tachykinin from the control current, showed no time-dependent inactivation, though its current-voltage relation also revealed inward rectification, with the reversal potential being approximately equal to the potassium equilibrium potential, Vk. 5. The relation between the substance P-sensitive chord conductance and voltage could be fitted by a Boltzmann equation, with changes in [K+]o shifting this relation along the voltage axis roughly in parallel with the shift in Vk. The maximum conductance was proportional to [( K+]o). 6. Cs+ (0.1 mM) blocked the substance P-sensitive current in a voltage-dependent manner, with an equivalent valency for Cs+ of 1.9. Barium blockage of the substance P-sensitive current was less voltage dependent. 7. Replacement of external Na+ by tetramethylammonium (TMA+) ions reduced the substance P-sensitive current by only 18%. 8. These results indicate that substance P inhibits potassium channels with inward rectifier properties very similar to those of skeletal muscle. 9. Application of sodium nitroprusside did not alter the effect of substance P, suggesting that cyclic GMP plays no role in the channel modulation.
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PMID:Modulation of inwardly rectifying channels by substance P in cholinergic neurones from rat brain in culture. 170 Jan 8

Activity-dependent expression of vasoactive intestinal peptide (VIP) was investigated in spinal cord/dorsal root ganglia cultures derived from embryonic mice. Since all spinal cord neurons appear to exhibit spontaneous action potentials after one week in vitro, activity-dependent regulation of VIP-transcripts (mRNAVIP) could be studied with or without electrical blockade induced by tetrodotoxin (TTX). In 10-day-old cultures, a 50% decrease in mRNAVIP was observed after 3 days of treatment with TTX. The decrease in mRNAVIP was reversed upon removal of the TTX and was dependent on the age of the cultures: no decreases from control were observed in 5-day-old cultures and much smaller decrements were produced in one month old cultures treated with TTX. A variety of neuroactive substances were tested for effects on mRNAVIP in electrically active and electrically blocked cultures. Application of 8-bromo-cAMP (cAMP), N-methyl-D-aspartate (NMDA), substance P, muscimol, A23187 and VIP to electrically active cultures resulted in a 2- to 3-fold increase in mRNAVIP, while phorbol myristate 13-acetate (PMA) and 8-bromo-cGMP (cGMP) had no effect. In contrast, electrically inactive cultures exhibited a 3 to 4-fold increase in mRNAVIP after treatment with PMA, cAMP and VIP, while NMDA, substance P, muscimol, A23187 and cGMP produced no increases. In summary, the regulation of VIP gene expression in embryonic spinal cord neurons shows a temporal sensitivity to TTX-induced electrical blockade and may be mediated by multiple neurotransmitter inputs which converge on cAMP- and calcium-related processes in an activity-dependent manner.
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PMID:Spontaneous electrical activity regulates vasoactive intestinal peptide expression in dissociated spinal cord cell cultures. 171 67

1. In isolated heart muscle preparations, selective removal of the endocardium results in a characteristic and unusual negative inotropic effect. Possible mechanisms for this effect were investigated in this study. 2. In endocardium-intact preparations of ferret papillary muscle, 8-bromo-cyclic GMP, sodium nitroprusside, atrial natriuretic peptide (ANP) and substance P each induced changes in contractile behaviour similar to selective endocardial removal, and each significantly elevated myocardial cyclic GMP levels. Substance P failed to elevate myocardial cyclic GMP levels following removal of endocardium or in the presence of haemoglobin, suggesting that it may act by releasing endothelium-derived relaxing factor (EDRF) from endocardium. However, there was no change in myocardial cyclic GMP levels following endocardium removal alone. 3. In cascade bioassay experiments, it was confirmed that porcine cultured endocardial cells released an unstable humoral agent whose effects on an endothelium-denuded pig coronary artery were indistinguishable from EDRF. 4. The negative inotropic effects of endocardium removal were reversed in bioassay experiments where an endocardium-denuded papillary muscle was exposed to the effluent from a column of porcine cultured endocardial cells on microcarrier beads. This demonstrates for the first time the release of a 'contraction prolonging factor' from endocardium, the tonic release of which would explain the negative inotropic effect of endocardium removal. 5. It is concluded that elevation of ferret papillary muscle cyclic GMP (as for example with EDRF) produces changes in contractile performance similar to those induced by endocardium removal. We also demonstrate that superfused porcine cultured endocardial cells release a humoral agent (provisionally named 'endocardin') which causes reversal of the changes in mechanical properties seen after endocardial removal.
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PMID:Factors released from endocardium of the ferret and pig modulate myocardial contraction. 171 74

The action of histamine on human dermal microvascular endothelial cells and modulation of its effects by the cytokine interleukin-1 and the vasoactive neuropeptide substance P have been investigated. Histamine (10(-6)-10(-3) M) induces release of prostaglandin E2 in a concentration- and time-dependent manner. Prostaglandin E2 release is facilitated principally by histamine H1 receptors as the H1 receptor antagonist pyrilamine attenuates prostaglandin E2 release whereas the H2 receptor antagonist cimetidine only slightly reduces release. In contrast to other cells, the histamine/receptor interaction is not associated with increased intracellular accumulation of the cyclic nucleotides, cyclic AMP, or cyclic GMP. Interleukin-1 induces a concentration-dependent release of prostaglandin E2 following 24 h incubation. However, substance P does not increase release of prostaglandin E2 above baseline. In cells incubated with 1 U/ml human recombinant interleukin 1 alpha for 24 h prior to stimulation with histamine (10(-5)-10(-3) M) for 30 min, there is a significant potentiation of histamine-induced release of prostaglandin E2 (p less than 0.05). Using a solubilized cell sonicate prepared from human dermal microvascular endothelial cells incubated with 1 U/ml human recombinant interleukin 1 alpha for 24 h, conversion of exogenous arachidonic acid into prostaglandin E2 increased by 60.19 +/- 18.28%. Cycloheximide partially reduces the increased conversion but completely blocks interleukin-1-induced release of prostaglandin E2 from intact cells. Substance P does not potentiate histamine-induced release of prostaglandin E2 or increase arachidonic acid conversion. These results demonstrate that human dermal microvascular endothelial cells are responsive to histamine and that interleukin-1, but not substance P, can potentiate histamine-induced release of prostaglandin E2. Interleukin-1 appears to act, at least in part, by regulating the availability of free arachidonic acid. Interactions between histamine and interleukin-1 may be important in the modulation of inflammatory reactions in skin.
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PMID:Responses of human dermal microvascular endothelial cells to histamine and their modulation by interleukin 1 and substance P. 171 8

The human gastroepiploic artery has been used as a coronary artery bypass conduit in a limited number of clinical studies. It has been postulated that the capacity of the endothelium to release vasoactive substances may contribute to differing patency rates observed in established bypass grafts. We have now examined endothelial function in the human gastroepiploic artery. Endothelium-dependent relaxations to substance P were observed. A maximum relaxation of 83.25% +/- 8.2% (mean +/- standard error) was attenuated to 48.5% +/- 16.4% in the presence of L-NG-monomethyl-arginine, a specific inhibitor of endogenous nitric oxide synthesis. Removal of the endothelium abolished the relaxations. With a specific radioimmunoassay, concomitant changes in levels of cyclic guanosine 3',5'-monophosphate, the second messenger that elicits smooth muscle relaxation after release of the endothelium-derived relaxing factor, were measured. It was found that the gastroepiploic artery had significantly higher resting and stimulated levels of cyclic guanosine 3',5'-monophosphate than either the internal mammary artery or the saphenous vein. In the presence of the cyclooxygenase inhibitor indomethacin, and indomethacin plus L-NG-monomethylanginine, the maximum relaxation was decreased to 70% +/- 9.5% and 59% +/- 10.8%, respectively. Our data demonstrate that endothelium-derived relaxing factor and prostacyclin may exhibit synergy in the control of vascular tone in this vessel. It is concluded that the endothelium of the gastroepiploic artery has a strong capacity to secrete vasodilators and inhibitors of platelet activity. This could have important influence on long-term patency.
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PMID:Endothelial function of human gastroepiploic artery. Implications for its use as a bypass graft. 836 Dec 5

The great discovery by Furchgott of the relaxing factor released from the endothelium (EDRF) awakened us to the necessity to reevaluate the functional importance of endothelial cells that have been chemically or physically stimulated. EDRF was first demonstrated to be released by acetylcholine, substance P, bradykinin and calcium ionophore A23187; thereafter, many substances have been found to release EDRF. This factor is quite unstable, is not produced by cyclooxygenase, and is an activator of soluble guanylate cyclase that synthesizes cyclic GMP; its action is suppressed by antioxidants via the superoxide anions produced, potentiated by superoxide dismutase and abolished by methylene blue and oxyhemoglobin. Recently, the role of lipoxygenase products in the production of EDRF was evaluated with new 5-lipoxygenase inhibitors without antioxidant activity. During the last couple of years, the actions and chemical properties of EDRF were verified to be quite similar to those of nitric oxide (NO); therefore, the hypothesis of "EDRF = NO" is widely being accepted. NO is produced from L-arginine via catalysis by an enzyme that is activated by Ca2+. The enzyme activity is inhibited by L-monomethyl arginine and other L-arginine analogs. Chemical and physical stimulations increase intracellular Ca2+ in endothelial cells that seems to be associated with K(+)-channel opening and hyperpolarization. Current interests are directed to the possible roles of NO in the regulation of nerve function. There are evidences suggesting that NO modulates adrenergic nerve function in blood vessels and some brain cell functions regulated by cellular cyclic GMP. Particularly, NO may be a transmitter substance in non-adrenergic, non-cholinergic vasodilator nerves innervating the cerebral arteries. Future investigations will determine the physiological roles of EDRF or NO and its relationships to pathophysiology of vascular dysfunctions, such as vasospasm and those related to hypertension, diabetes, aging, etc., and the extended roles of NO in nerve function, inflammation, immune reactions, etc. would be clarified more extensively by accelerated progress in this field of research.
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PMID:[Endothelium-derived relaxing factor (EDRF)]. 216 93

The response to small peptides such as Arg-vasopressin, oxytocin and tachykinins was investigated in cultured porcine aortic endothelial cells. The production of endothelium-derived nitric oxide was assessed indirectly by the accumulation of cyclic GMP, a response that is due to the increased activity of soluble guanylate cyclase of the endothelial cells after release of the mediator. Arg-vasopressin, oxytocin, substance P and physalae-min (an analog of substance P, pGlu-Ala-Asp-Pro-Asn-Lys-Phe-Tyr-Gly-Leu-Met-NH2) markedly and transiently stimulated the production of cyclic GMP without affecting that of cyclic AMP. Treatment of endothelial cells with either hemoglobin or methylene blue reduced significantly both the basal and stimulated level of cyclic GMP. The production of cyclic GMP evoked by Arg-vasopressin and substance P was inhibited selectively by NG-monomethyl-L-arginine but not by its D-enantiomer. The neurohypophyseal hormones and related peptides stimulated the accumulation of cyclic GMP in a concentration-dependent manner, with the following relative order of potency: oxytocin greater than Lys-vasopressin greater than Arg-vasopressin much greater than [deamino-Cys1, D-Arg8]-vasopressin. The production of cyclic GMP evoked by oxytocin was inhibited selectively by [d(CH2)5, Tyr(OMe)2, Orn8]-vasotocin, an oxytocin antagonist. The production of cyclic GMP evoked by Arg-vasopressin and Lys-vasopressin was inhibited by [beta-mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin, a selective V1-receptor antagonist. The moderate production of cyclic GMP evoked by [deamino-Cys1, D-Arg8]-vasopressin was inhibited significantly by the V1-receptor antagonist. The peptide antagonists affected only minimally or not at all the production of cyclic GMP evoked by a donor of nitric oxide, SIN-1 (3-Morpholino-Sydnonimine). These observations indicate that 1) neurohypophyseal hormones and tachykinins stimulate the accumulation of cyclic GMP in cultured porcine aortic endothelial cells by increasing the production of endothelial-derived nitric oxide, which in turn enhances the activity of soluble guanylate cyclase; 2) the production of cyclic GMP in response to oxytocin is due to activation of oxytocinergic receptors; and 3) the production of cyclic GMP evoked by Arg-vasopressin and Lys-vasopressin is due mostly to activation of V1-vasopressinergic receptors.
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PMID:Neurohypophyseal peptides and tachykinins stimulate the production of cyclic GMP in cultured porcine aortic endothelial cells. 217 9

The peptic glands, which are located in the mucosa of the distal esophagus in the frog, respond to multiple stimuli. In vitro studies were performed, using mucosal sheets of the esophagus of Rana catesbeiana, during the summer months when the glands are fully responsive to determine whether the receptors for the stimuli [cholinergic, beta-adrenergic, and peptidergic (bombesin but not cholecystokinin)] are specific to the stimuli. Through the use of three classes of antagonist, we found that 1) atropine defined the muscarinic nature of the bethanechol stimulation, 2) propranolol defined the beta-adrenergic nature of stimulation by isoproterenol, and 3) the substance P analogue [D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P was specific for the peptide bombesin. No cross-inhibition was seen, and dibutyryl cGMP did not inhibit any of the three stimuli. Moreover, any two of the three stimuli in combination stimulated more pepsinogen than either alone but the same as the sum of the two individual responses. Both lines of evidence indicate that there are at least three independent receptor pathways for stimulation of pepsinogen secretion in these glands.
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PMID:Interaction between stimuli and their antagonists on frog esophageal peptic glands. 241 91

In light of current interest in substance P as a bronchoconstrictor, several pharmacologic antagonists of known mediators of anaphylaxis were tested for possible activity against this neuropeptide. Concentration-dependent contractions of the isolated guinea-pig tracheal strips to substance P (10(-8) to 10(-5) M) were elicited. These contractions were inhibited by substance P receptor antagonists, D-Arg1-D-Trp7,9-Leu11 and D-Pro2-D-Trp7,9-substance P (10(-6) to 10(-4) M). Substance P-induced contractions were not inhibited by histamine, alpha and beta adrenergic receptor antagonists or by cyclooxygenase inhibition. However, atropine enhanced contractions to substance P. Both vasoactive intestinal polypeptide (10(-7), 10(-6) and 10(-4) M) and isoproterenol (10(-7) M) were able to reverse an ongoing substance P (10(-5) M)-induced contraction. Also, at a concentration of 10(-5) M, substance P increased cyclic GMP accumulation, but had no effect on the concentration of cyclic AMP. A 15-min pretreatment with either verapamil or nifedipine (10(-8) M) had no effect on substance P-induced contractions, whereas the purported intracellular Ca++ antagonist, 8-[N,N-diethylamino]-octyl 3,4,5-trimethoxybenzoate hydrochloride (10(-4) M) produced a rightward shift of a substance P concentration-response curve. A selective calmodulin inhibitor, N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (10(-4) M) failed to affect the contraction produced by 10(-5) M substance P. When guinea-pig tracheal strips were washed and allowed to re-equilibrate in 0 Ca++ buffer, the initial maximum contractions to substance P (10(-5) M) were equal for both regular (1.8 mM) Ca++ and 0 Ca++ buffer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of substance P-induced contractions of guinea-pig trachea. 242 83

The dependence of vascular relaxation on an intact endothelium and the relationship between relaxation and cyclic GMP accumulation were determined in coronary arteries isolated from cardiac transplantation patients with or without coronary atherosclerosis. In nonatherosclerotic arteries, the endothelium-dependent agent acetylcholine produced concentration-related relaxations. In atherosclerotic arteries, endothelium-dependent relaxations were abolished with acetylcholine, partly suppressed with substance P and histamine, and completely preserved with the ionophore A23187. In these arteries, the endothelium-independent agent nitroglycerin remained fully active. Accumulation of cyclic GMP in atherosclerotic strips was suppressed with acetylcholine but unattenuated with A23187 and nitroglycerin. In aortas from rabbits with diet-induced atherosclerosis, there was likewise an impaired cholinergic relaxation and cyclic GMP accumulation in the presence of preserved responses to A23187 and nitroglycerin. The results demonstrate that impaired cholinergic responses in atherosclerotic arteries reflect a muscarinic defect and not an inability of endothelium to release endothelial factor or smooth muscle to respond to it.
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PMID:Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. 243 88


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