UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of various local anesthetics and other substances known to modify calcium fluxes in cells, on submaximal responses of guinea-pig ileum to substance P, acetylcholine, histamine and barium chloride was determined. Procaine caused a dose-related depression of the response to all the agonists but the response to substance P was far less susceptible to this depression. Lidocaine, bupivacaine, pramoxine and W 6211 also caused a lower degree of attenuation of the response to substance P than the responses to acetylcholine, histamine and barium chloride. Verapamil caused a dose-related depression of responses to all the agonists equally. The use of calcium-free solutions abolished responses to substance P, acetylcholine and histamine. The response to barium chloride was less affected by calcium withdrawal but was reduced markedly. In the presence of 10 mM lanthanum chloride, the response to all the agonists was abolished. The relative resistance of the substance P responses to antagonism by local anesthetics suggests that different and more efficient channels for calcium entry into the smooth muscle cell are involved.
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PMID:Interactions between local anesthetics and spasmogens on the guinea-pig ileum. 93 95

We examined the direct effect of motilin on longitudinal and circular smooth muscle cells isolated from the guinea pig small intestine. In addition, the effects of 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxy-benzoate hydrochloride (TMB-8, an inhibitor of intracellular Ca(2+)-release), verapamil (a voltage-dependent Ca(2+)-channel blocker), and removal of extracellular Ca2+ were investigated to evaluate the role of intracellular Ca2+ stores and extracellular Ca2+ on the muscle contraction induced by motilin. The effects of atropine (a muscarinic receptor antagonist), spantide (a substance P receptor antagonist) and loxiglumide (a CCK-receptor antagonist) were also examined to determine whether the motilin-induced contraction was independent of those receptors. Motilin induced a contraction of the longitudinal and circular smooth muscle cells in a dose-dependent manner with the maximal effect attained after 30 seconds of incubation. The ED50 values were 0.3 nM and 0.05 nM, respectively. TMB-8 suppressed completely the motilin-induced contraction of both types of smooth muscle cells. Verapamil had only a slight suppressive effect. Removal of extracellular Ca2+ did not have any significant influence on motilin-induced contraction. The contractile response to motilin was not affected by atropine, spantide or loxiglumide. Our findings showed that:1) motilin has a direct contractile effect on both longitudinal and circular smooth muscle cells; 2) this contractile effect is not evoked via muscarinic, substance P or CCK receptors, and 3) the intracellular release of Ca2+ plays an important role in the contractile response to motilin on both types of smooth muscle cells.
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PMID:Direct contractile effect of motilin on isolated smooth muscle cells of guinea pig small intestine. 138 65

In intact sheets of the guinea pig ileal longitudinal muscle, loaded with fura-2, both substance P (SP)- and K(+)-induced contractile responses are preceded by cytoplasmic free Ca2+ ([Ca2+]i) variations. In response to SP (10(-10)-10(-7) M), [Ca2+]i and force increased concentration dependently. From 10(-9) M on, the response was biphasic: an initial Ca2+ spike and force transient were followed by a tonic component. The [Ca2+]i and force vs. log [SP] curves were sigmoidal for the initial phasic component, while a homologous receptor desensitization caused a reduced tonic component of the [Ca2+]i and contractile response at higher concentrations of SP. Both intracellular Ca2+ release and Ca2+ influx play a role in the effect of the peptide. In depolarizing solutions (140 mM K+) and in Ca2(+)-free medium (2 mM EGTA), SP induced a transient increase in [Ca2+]i and force. The Ca2+ stores used by SP and acetylcholine (ACh) overlap. [Ca2+]i and force fell to base-line levels when the extracellular Ca2+ was reduced from 1.2 to 0.2 mM during stimulation with SP. Verapamil reduced the tonic response. We also studied the relation between [Ca2+]i and force for the peak and steady-state values after stimulation with increasing concentrations of SP and K+. The phasic force response was linearly related to log [Ca2+]i. During the sustained response to K+, the Ca2+ sensitivity of the contractile/regulatory proteins was decreased, whereas no changes were observed during prolonged stimulation with the peptide.
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PMID:Effects of substance P on [Ca2+]i and force in intact guinea pig ileal smooth muscle. 169 85

The effects of substance P (SP), [D-Pro2, D-Trp7,9]SP and verapamil on the electric activity of B cells of Langerhans islets of mice were investigated. Addition of SP 100 nmol.L-1 to the perfusion medium stimulated spontaneous electric activity induced by glucose 5.5 mmol.L-1 with an increase in frequency and amplitude of the spikes. [D-Pro2, D-Trp7,9]SP 50 nmol.L-1 reversed the stimulative effect of SP. There was no evidence for an enhancing interaction between SP and acetylcholine 1 mumol.L-1. Verapamil 60 mumol.L-1 blocked the stimulative effect of SP. These results suggest that the stimulative effect of SP on the electric activity of B cells may be due to the increase in Ca2+ influx through the voltage-dependent Ca2+ channels.
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PMID:Effects of substance P on electric activity of mouse pancreatic islet cells in vitro. 172 68

Calcium plays a central role in modulating many physiologic events. We have investigated the role of calcium channel blockade in the control of basal (n = 6)- and substance P-stimulated (n = 6) intestinal transport in the isolated perfused rabbit ileum. Twenty-centimeter segments of ileum, harvested from New Zealand rabbits, were arterially perfused at 1.5 ml/min with an oxygenated modified Krebs buffer solution containing washed human red cells (Hct = 15-20%) and 2.5 mM Ca2+. The intestinal lumen was perfused at 2 ml/min with an isotonic solution containing 1.2 mM Ca2+ and [14C]PEG as a nonabsorbable volume marker. The infusion of verapamil (1 microgram/min) significantly reduced (P less than 0.05) the basal secretion of H2O, and Cl-. Verapamil prevented the secretory effect of substance P infused at 0.25 microgram/min. Intraarterial verapamil had no effect on vascular perfusion pressure. These data indicate that calcium channel blockade has significant effects on basal- and substance P-stimulated intestinal secretion and suggest that transmembrane calcium fluxes function as major determinants of basal- and secretagogue-stimulated intestinal transport.
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PMID:The effect of calcium channel blockade on basal- and substance P-induced intestinal secretion. 245 37

Following irritation of the airway, the ciliostimulatory effects of the tachykinin, substance P (SP), are thought to be secondary to mucus release. We hypothesized that SP also induces small increases in ciliary beat frequency (CBF) via a calcium-mediated process. Brushed ciliated cells from the nasal epithelium of healthy human subjects were suspended in tissue culture fluid and the acute effects of SP upon these cells were studied in a mucus-free environment. In some preparations, changes in CBF in response to SP were measured with a video-based system. The effect of an SP antagonist, of Ca2+ channel block with verapamil, and of the calcium analogue lanthanum on the SP response were also tested. In other preparations, the ciliated cells were preloaded with Fura-2, a dye which fluoresces with Ca2+ ions, and the response of intracellular Ca2+ to SP was monitored. SP (10(-9)-10(-6) M) transiently increased CBF in a dose-dependent manner, with the maximal response occurring at 10 min. The response was small, with a maximum increase of 8.9%. The SP receptor antagonist (D-pro2,D-trp7,9)-SP (10(-5) M) abolished this effect. Verapamil (10(-5) M) attenuated the response to SP (10(-7) M), whilst lanthanum chloride (250 microM) abolished it. Inhibition of SP destruction by phosphoramidon (10(-6) M) also eliminated the transient rise in CBF. However, compared to SP alone, the combination of SP and phosphoramidon induced a novel delayed lanthanum-sensitive rise in CBF. In other experiments, SP (10(-7) M) induced a transient increase in free intracellular Ca2+ concentration (maximal rise 73%), which returned to baseline before the expected onset of the CBF response. We conclude that substance P induces either a transient or sustained increase in CBF dependent on the rate of destruction of this peptide around tachykinin receptors. These receptors are likely to be linked to lanthanum- and verapamil-sensitive pathways for the entry of Ca2+ into cells. The small magnitude of the rise in CBF makes its physiological role uncertain at present.
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PMID:Interaction between calcium, neutral endopeptidase and the substance P mediated ciliary response in human respiratory epithelium. 883 39

Changes in the background impulse activity of midbrain central gray substance neurons have been studied on slice preparations from the rat midbrain upon application of calcium-free solution, an activator of calcium channels, BAY-K 8644 (10 nM), organic (verapamil, 40 microM; D600, 10 microM; nifedipine, 1-10 microM; amiloride, 1 microM) and inorganic (Co2+, 1.5 mM) calcium channel blockers. Besides BAY-K 8644, all the substances inhibited most of the neurons studied. Verapamil, BAY-K 8644 and Co2+ also revealed facilitatory effects. Facilitatory action of BAY-K was most effective in silent neurons and in those previously inhibited by amiloride. Latent period values of inhibition in calcium-free solution and upon application of organic and inorganic blockers have the following sequence: D600 > amiloride > verapamil > Co2+ > nifedipine > calcium-free solution. Maximum rise time had the following order: amiloride > D600 > nifedipine > verapamil > Co2+ > calcium-free solution. Complete suppression of the neuronal activity induced by amiloride lasted twice as long as that induced by calcium-free solution, Co2+ and nifedipine, and six times as long as verapamil-induced suppression. Preliminary application of calcium channel blockers reduced facilitatory and increased inhibitory effects of serotonin and substance P. Data obtained are discussed with the supposition in mind that inhibition of the function of calcium channels in central gray substance neurons could be one of the mechanisms underlying the analgesic effect of a series of neurotropic agents after their introduction into this structure.
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PMID:Modulation of the activity of midbrain central gray substance neurons by calcium channel agonists and antagonists in vitro. 884 21

The changes induced in the mean arterial blood pressure of anaesthetised rats following the administration of armed spider (Phoneutria nigriventer) venom have been investigated. The intravenous injection of Phoneutria nigriventer venom (0.1 mg/kg) evoked a brief and reversible decrease in the mean arterial blood pressure whereas a higher dose of venom (0.3 mg/kg) caused a biphasic response characterized by a short-lasting hypotension followed by a sustained and prolonged hypertension (40-50 min). These changes were accompanied by tachycardia, salivation, fasciculations, defecation and respiratory disturbances. Pretreatment of the animals with atropine (10 mg/kg), propranolol (100 mg/kg), phenoxybenzamine (100 mg/kg) and indomethacin (4 mg/kg) did not significantly affect the mean arterial blood pressure changes induced by Phoneutria nigriventer venom. Similarly, the bradykinin B2 receptor antagonist Hoe 140 (D-Arg-[Hyp3,Thi5,DTic7,Oic8]-bradykinin) (0.6 mg/kg), the PAF receptor antagonist WEB 2086 (3-(4-(2-chlorophenyl)-9-methyl-6H-thieno-(3,2f) (1,2,4)-triazolo-(4,3-a) (1,4)-diazepine-2-yl)-(4-morpholinyl)-1-propanone) (20 mg/kg), the tachykinin NK1 receptor antagonist SR 140333 ((S)1-(2-[3-(3,4-dichlorophenyl)-1-(3-iso-propoxyphenyl acetyl) piperidin-3-yl] ethyl)-4-phenyl-1-azoniabicyclo[2.2.2] octane, chloride) (0.5 mg/kg), the tachykinin NK2 receptor antagonist SR 48968 ((S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophen yl) butyl]benzamide) (0.5 mg/kg) and the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (10 mg/kg) had no significant effect on the mean arterial blood pressure changes induced by Phoneutria nigriventer venom. The increase in the blood pressure induced by Phoneutria nigriventer venom was also not significantly affected by either the angiotensin II receptor antagonist losartan (10 mg/kg) or the endothelin ETA receptor antagonist FR 139317 ((R)2-[(R)-2-[[1-(hexahydro-1H-azepinyl]carbonyl]amino-4-methyl- pentanoyl]amino-3-[3-(1-methyl-1H-indoyl)]propionyl] amino-3-(2-pyridyl) propionic acid) (30 mg/kg). The ATP-dependent K+ channel antagonist glibenclamide (50 mg/kg) reduced by 40% the hypotension induced by Phoneutria nigriventer venom without affecting the hypertensive response. Pretreatment of the animals with L-type Ca2+ channel antagonists such as verapamil (10-100 micrograms/kg/min), diltiazem (40-120 micrograms/kg/min) and nifedipine (0.3-10 mg/kg) markedly attenuated the hypertension induced by Phoneutria nigriventer venom. Verapamil (30 micrograms/kg/min) and diltiazem (120 micrograms/kg/min) also promptly reversed the established hypertension induced by Phoneutria nigriventer venom when infused 8 min after venom injection. Our results indicate that the brief decrease of blood pressure induced by Phoneutria nigriventer venom is partially due to ATP-dependent K+ channel activation. The prolonged hypertension seems to result from direct Ca2+ entry into vascular and/or cardiac muscles.
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PMID:The effect of Phoneutria nigriventer (armed spider) venom on arterial blood pressure of anaesthetised rats. 886 97

Tachykinins are present in the anterior pituitary gland and there is evidence that they may have a direct intrapituitary role influencing the secretion of some of the hormones released by this gland. In this investigation, we have studied the effect of the non-peptide NK-2 receptor antagonist SR 48,968 (Sanofi Recherche) on the basal release of LH, FSH, and prolactin by rat hemipituitaries incubated in vitro, and also on the response to GnRH. SR 48,968 significantly inhibited prolactin release into the medium. The highest doses of this compound stimulated the basal release of LH by hemipituitaries from castrated, castrated testosterone-treated, and ovariectomized estradiol-treated rats, but not from intact male rats. SR 48,968 significantly inhibited the release of LH in response to GnRH. Since some tachykinin receptor antagonists have been demonstrated to act also on calcium channels, studies with verapamil, a calcium channel antagonist, were also carried out for comparison. Verapamil inhibited prolactin release into the medium and decreased the LH response to GnRH. These results suggest that tachykinins that bind NK-2 receptors, may have an intrapituitary role stimulating the release of prolactin, and that they may also modulate the response of the gonadotrophs to GnRH. The fact that verapamil shares some of the actions exerted by NK-2 receptor antagonists on the pituitary glandm however, suggests the possibility that some of the effects of NK-2 receptor antagonists may be mediated through calcium channel antagonism. Therefore, the results observed with the use of some of these antagonists should be interpreted with great caution.
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PMID:Effect of a non-peptide NK-2 tachykinin receptor antagonist on LH, FSH, and prolactin release by rat hemipituitaries in vitro. 937 29

The nine Leucophaea Tachykinin-Related Peptides (LemTRP 1-9) isolated from the midgut and brain of the cockroach, Leucophaea maderae, all induced increases in spontaneous contractions of the L. maderae hindgut. Synthetic LemTRP 1 and 3-9, were equally potent in inducing contractions of the hindgut. More than seven of the nine C-terminal residues of the closely related locust peptide locustatachykinin I (LomTK I) are required for full activity of the peptide on the L. maderae hindgut. Proctolin, a well characterized myostimulatory neuropeptide, was shown to be more potent than LemTRPs. LemTRP 1 and proctolin did not have synergistic actions in potentiating the amplitude and tonus of contractions of the L. maderae hindgut. Several differences could be seen in actions of LemTRP 1 and proctolin. In contrast to proctolin, LemTRP 1 could not override the inhibitory action of 10(-9) M of the myoinhibitory peptide leucomyosuppressin. Spantide I, an antagonist of the mammalian tachykinin receptors, at a concentration of 5 microM, blocked the response to LemTRP 1, but not to proctolin. The competitive proctolin receptor antagonist [alpha-methyl-L-tyrosine2]-proctolin blocked the action of both proctolin and LemTRP 1 when applied at 1 microM, whereas cycloproctolin had no antagonist action on either peptide. Verapamil, a blocker of voltage gated Ca2+-channels, and the less specific Ca2+-channel blocker Mn2+, abolished the action of LemTRP 1, but not of proctolin. The results obtained indicate that LemTRPs act on receptors distinct from those of proctolin. Double label immunocytochemistry revealed that all LomTK-like immunoreactive fibers impinge on the proctolinergic fibers in the hindgut. This finding and the inhibitory actions of Ca2+-channel blockers on TRP responses and of the proctolin receptor antagonist on both peptides, may suggest that the LemTRP receptors are not on the hindgut muscle fibers but on the terminals of the proctolinergic neurons. Thus, LemTRPs may induce release of proctolin on the hindgut. An alternative is that LemTRPs act by mechanisms clearly distinct from those of proctolin.
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PMID:Characterization of actions of Leucophaea tachykinin-related peptides (LemTRPs) and proctolin on cockroach hindgut contractions. 953 32

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