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)

Single microelectrode voltage-clamp recordings were made from submucous neurons of the guinea-pig caecum. The slow excitatory postsynaptic current was compared with the currents induced by neurokinin A and substance P. The current induced by neurokinin A (100-300 nM) was associated with a decreased membrane conductance and reversed in polarity between -90 and -100 mV. The neurokinin A current was reduced by Co2+ (1-2 mM), but was not affected by Cs+ (1-2 mM), Ba2+ (10-100 microM) or low Cl- (20-40 mM) solutions. In about 80% of the neurons, the current induced by substance P (100-300 nM) was associated with a decreased membrane conductance and did not reverse with hyperpolarization of the membrane potential up to -130 mV. The current was reduced by Co2+ (1-2 mM) and augmented by low Cl- (20-40 mM) solutions, but was not affected by Cs+ (1-2 mM) or Ba2+ (10-100 microM)-containing solutions. In about 20% of the neurons, the substance P current reversed in polarity between -100 and -120 mV. The slow excitatory postsynaptic current elicited by repetitive nerve stimulation (10-40 Hz, three to five pulses) was accompanied by a decreased membrane conductance, and reversed in polarity between -90 and -100 mV. The slow excitatory postsynaptic current was abolished by Co2+ (1-2 mM) or low Na+ (12 mM) solutions, but was not affected by Cs+ (1-2 mM), Ba2+ (10-100 microM) or low Cl- (20-40 mM) solutions. In such neurons, the neurokinin A current was reversed at approximately the same potential at which the slow excitatory postsynaptic current was reversed, while the substance P current was not reversed even by much stronger hyperpolarizations. It was concluded that the neurokinin A current was mainly due to depression of potassium conductances, while the substance P current resulted from both increased anion conductance and decreased potassium conductances. The conductance change underlying the slow excitatory postsynaptic current is similar to that caused by neurokinin A.
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PMID:Neurokinin A mimics the slow excitatory postsynaptic current in submucous plexus neurons of the guinea-pig caecum. 753 3

We examined the effects of intrathecally administered neuropeptide Y on the spinal nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats with intact sciatic nerves, or 11-39 days after unilateral transection of the sciatic nerve. In rats with intact sciatic nerve, intrathecal neuropeptide Y at low doses (10 and 100 ng) caused a brief facilitation of the flexor reflex. At a dose of 300 ng, the effect of neuropeptide Y on the flexor reflex was biphasic, i.e. a brief facilitation followed by slight depression. At higher doses (1 and 10 micrograms), the effect of neuropeptide Y was mainly inhibitory, causing substantial and usually prolonged depression of the flexor reflex magnitude. The reflex depression caused by intrathecal neuropeptide Y was not reversed by the opioid antagonist naloxone or the alpha 2 adrenoceptor antagonist atipamezole. Intrathecal neuropeptide Y at doses up to 1 and 10 micrograms had no effect on reflex facilitation caused by conditioning stimulation of C-fibers, intrathecal substance P or neurokinin A. Topical application of neuropeptide Y (1 microgram/microliter) failed to influence the monosynaptic reflex in normal rats. Eleven to 16 days after peripheral axotomy, the initial excitation of the flexor reflex to intrathecal neuropeptide Y was significantly enhanced in axotomized compared with normal rats. However, the depressive effect of neuropeptide Y on the flexor reflex was unchanged. Neuropeptide Y did not influence the monosynaptic reflex in axotomized rats at this period. In experiments performed on rats in which the sciatic nerve had been transected 31-39 days previously, the facilitatory effect of neuropeptide Y on the flexor reflex remained enhanced compared with normal rats. Furthermore, the inhibitory effect of neuropeptide Y also increased as 100 ng intrathecal neuropeptide Y was able to produce reflex depression in a similar fashion as 300 ng neuropeptide Y normally and the reflex depression caused by 1 microgram neuropeptide Y was stronger and longer lasting than in normal rats. Intrathecal neuropeptide Y (100 ng-10 micrograms) in rats with intact sciatic nerves caused a moderate decrease in spinal cord dorsal surface blood flow as measured with a laser Doppler flowmeter. This effect of neuropeptide Y was unchanged in axotomized rats. The present results support previous observations that spinal application of neuropeptide Y in normal rats caused antinociception. As the depressive effect of neuropeptide Y is independent of spinal opioid and alpha 2-adrenergic systems, it may be mediated by its own receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effects of intrathecal neuropeptide Y on the spinal nociceptive flexor reflex in rats with intact sciatic nerves and after peripheral axotomy. 753 84

To determine the role that vasoactive neuropeptides, calcitonin gene-related peptide, and substance P play in tissue-blood flow regulation during early septic shock, we examined the responsiveness of arteries removed from pigs 3 h after administration of Escherichia coli lipopolysaccharide or saline vehicle. The carotid, cranial mesenteric, and left anterior descending coronary arteries were excised, and rings were cut from each vessel. Constrictor responses were obtained to cumulative doses of norepinephrine or potassium chloride. Rings were reconstricted and challenged with acetylcholine, substance P, calcitonin gene-related peptide, and nitroglycerin. Lipopolysaccharide significantly increased the cranial mesenteric artery's response to high concentrations of norepinephrine and the response to nitroglycerin in all vessels. This enhancement of responses to nitroglycerin suggests augmented smooth-muscle responsiveness to an exogenous source of nitric oxide, possibly associated with early depression of basal endothelial function. Depression of agonist-induced nitric oxide release may mask such enhancement with endothelial-dependent dilators and may enhance the response to adrenergic constrictors in some vascular beds.
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PMID:Early endotoxic shock results in enhanced vasodilator responses to nitroglycerin but unaltered responses to neuropeptides calcitonin gene-related peptide and substance P. 753 18

The existence of a septide-sensitive subtype of the tachykinin NK1 receptor has been recently proposed. In the rat isolated urinary bladder, the non-peptide NK1 receptor antagonist RP 67,580 exhibits a higher affinity towards septide (pKB 7.57) than towards [Sar9]substance P sulfone (pKB 7.00). In this study we have investigated the pharmacological profile of the non-mammalian tachykinin physalaemin, of the synthetic NK1 receptor agonist GR 73,632 (delta-aminovaleryl[LPro9,NMeLeu10]substance P(7-11)) and of [Glu(OBzl)11]substance P in relation to the putative existence of a septide-sensitive receptor. The activity of [Glu(OBzl)11]substance P at the NK1, NK2 and NK3 receptor was assayed in the guinea-pig ileum NK1 receptor assay (EC50 26 nM), in the rabbit pulmonary artery NK2 receptor assay (weak agonist activity) and in the rat portal vein NK3 receptor assays (no appreciable activity up to 1 microM). GR 73,632, [Glu(OBzl)11]substance P and physalaemin, all produced concentration-dependent contractions of the rat isolated urinary bladder, with EC50 values of 17, 79, and 9 nM, respectively. The responses to the three agonists were very slightly or not modified by the NK2 receptor antagonist SR 48,968 (1 microM). RP 67,580 (0.3-3 microM) produced a concentration-dependent rightward shift of the curve to GR 73,632, [Glu(OBzl)11]substance P and physalaemin without producing depression of their maximal response. Schild plot analysis indicated the competitive nature of the antagonism. The affinity (pKB) of RP 67,580 towards physalaemin, GR 73,632 and [Glu(OBzl)11]substance P was 7.12, 7.56 and 7.95, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GR 73,632 and [Glu(OBzl)11]substance P are selective agonists for the septide-sensitive tachykinin NK1 receptor in the rat urinary bladder. 753 5

1. This study analyses the receptors mediating the effects of bradykinin (BK) and analogues on neurogenic twitch contractions of the mouse isolated vas deferens evoked, in the presence of captopril (3 microM), by electrical field stimulation with trains of 4 rectangular 0.5 ms pulses of supramaximal strength, delivered at a frequency of 10 Hz every 20 s. 2. BK (0.1-300 nM) induced a graded potentiation of twitches, with an EC50 (geometric mean and 95% confidence limits) of 4.5 nM (1.7-11.6) and an Emax of 315 +/- 19 mg per 10 mg of wet tissue (n = 6). Similar results were obtained in tissues challenged with Lys-BK, [Hyp3]-BK, Met,Lys-BK and the selective B2 receptor agonist [Tyr(Me)8]-BK (0.1-300 nM). 3. The selective B2 receptor antagonists, Hoe 140 (1-10 nM) and NPC 17731 (3-30 nM), caused graded rightward shifts of the curve to BK-induced twitch potentiation, yielding apparent pA2 values of 9.65 +/- 0.09 and 9.08 +/- 0.13, respectively, and Schild plot slopes not different from 1. Both antagonists (100 nM) failed to modify similar twitch potentiations induced by substance P (3 nM) or endothelin-1 (1 nM). Preincubation with the selective B1 receptor antagonist, [Leu8,des-Arg9]-BK (1 microM), increased the potentiating effect of BK on twitches at 30-300 nM. 4. In contrast to BK, the selective B1 receptor agonist, [des-Arg9]-BK (0.3-1000 nM) reduced the amplitude of twitches in a graded fashion, with an IC50 of 13.7 nM (10.4-16.1) and an Imax of 175 +/- 11 mg (n = 4). The twitch depression induced by [des-Arg9]-BK (300 nM) was not affected by Hoe140 (30nM) or NPC 17731 (100nM), but was abolished by the selective B1 receptor antagonist,[Leu8,des-Arg9]-BK (1 microM), which did not modify the twitch inhibitory effect of clonidine (1 nM) or morphine (300 nM).5. In non-stimulated preparations, BK (100 nM) also potentiated, in a Hoe 140-sensitive (10 nM)manner, the contractions induced by ATP (100 microM), but not by noradrenaline (10 microM), whereas[des-Arg9]-BK (300 nM) did not modify the contractions induced by either agonist.6. It is concluded that the mouse vas deferens expresses both B1 and B2 receptors, which modulate sympathetic neurotransmission in opposing ways. Neurogenic contractions are inhibited by stimulation of possibly prejunctional B, receptors, whereas activation of B2 receptors increases twitch contractions,in part by amplifying the responsiveness of the smooth muscle cells to the sympathetic co-transmitter ATP.
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PMID:Characterization of kinin receptors modulating neurogenic contractions of the mouse isolated vas deferens. 760 50

1. The ability of capsazepine, a recently developed capsaicin receptor antagonist, to prevent the effects of capsaicin on the rat isolated urinary bladder (contraction) and vas deferens (inhibition of electrically-evoked twitches) was compared to that of ruthenium red, a dye which behaves as a functional antagonist of capsaicin. 2. In the rat bladder, capsazepine (3-30 microM) produced a concentration-dependent rightward shift of the curve to capsaicin without any significant depression of the maximal response to the agonist. By contrast, ruthenium red (10-30 microM) produced a non-competitive type of antagonism, characterized by marked depression of the maximal response attainable. Similar findings were obtained in the rat isolated vas deferens in which capsazepine (10 microM) produced a rightward shift of the curve to capsaicin while ruthenium red (3 microM) depressed the maximal response to the agonist. 3. At the concentrations used to block the effect of capsaicin, neither capsazepine nor ruthenium red affected the contractile response of the rat urinary bladder produced by either neurokinin A or electrical field stimulation or the twitch inhibition produced by rat alpha-calcitonin gene-related peptide (alpha CGRP) in the vas deferens. 4. These findings provide additional evidence that both capsazepine and ruthenium red are valuable tools for exploration of the function of capsaicin-sensitive primary afferent neurones. The antagonism of the action of capsaicin by capsazepine is entirely consistent with the proposed interaction of this substance with a vanilloid receptor located on primary afferents, while the action of ruthenium red apparently involves a more complex, non-competitive antagonism.
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PMID:A comparison of capsazepine and ruthenium red as capsaicin antagonists in the rat isolated urinary bladder and vas deferens. 768 39

The effects of substance P and the selective neurokinin-1 receptor antagonist (+/-)-CP-96,345 have been compared on in vitro spinal cord preparations from the rat and the gerbil. Substance P produced a concentration-dependent depolarization of motoneurons recorded from ventral roots of both species. The EC50 values (microM mean +/- S.E.M.) obtained in rat (0.95 + 1.0/-0.49) and gerbil (0.47 + 0.26/-0.17) preparations were comparable. The mean maximal depolarization (mV mean +/- S.E.M.) evoked in rat (2.07 + 0.26/-0.25) was approximately two-fold greater than that evoked in gerbil (1.21 + 0.15/-0.14) preparations. In the rat substance P had a biphasic effect (depression followed by potentiation) on the short latency probably monosynaptic reflex evoked by electrical stimulation of a dorsal root. In gerbil preparations substance P produced only potentiation of the monosynaptic reflex. The EC50 values (microM) mean +/- S.E.M.) for this potentiating action in rat (0.97 + 0.75/-0.43) and gerbil (0.46 + 3.6/-0.4) preparations were similar. This potentiation demonstrates a positive modulation of an endogenous excitatory probably glutamatergic transmission by substance P in the ventral horn of the spinal cord. The depressant phase observed in rat preparations may be related to the relative immaturity of myelination in rat ventral root fibres compared to the gerbil. The selective neurokinin-1 antagonist (+/-)-CP-96,345 was one hundred-fold less potent as an antagonist of substance P-induced depolarizations in the rat (pA2 4.69 +/- 0.18, n = 7) than in the gerbil (pA2 6.79 +/- 0.16, n = 5) spinal cord. This finding suggests that (+/-)-CP-96,345 may not act solely at the neurokinin-1 recognition site. In conclusion this study demonstrates that substance P modulates the monosynaptic reflex in the spinal cord presumably via activation of neurokinin-1 receptors.
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PMID:The modulation of the monosynaptic reflex by substance P in the hemisected spinal cord preparation of the rat and gerbil. 769 48

Two halogenated cyclobutanes, one anesthetic and one not, were compared on receptor-specific pathways in isolated neonatal rat spinal cord. The anesthetic 1-chloro-1,2,2-trifluorocyclobutane depressed the monosynaptic reflex (glutamate non-NMDA receptors) and abolished a slow ventral root potential (glutamate NMDA, non-NMDA and tachykinin receptors). This compound slightly enhanced the muscimol-evoked dorsal root potential (GABAA) but reversibly depressed the dorsal root potential elicited by dorsal root stimulation. The non-anesthetic 1,2-dichlorohexafluorocyclobutane increased monosynaptic reflex, depressed slow ventral root potential approximately 50%, had little effect on muscimol-evoked dorsal root potential, and irreversibly depressed dorsal root-evoked dorsal root potential. Hypoxia accounts for slow ventral root potential depression, but not monosynaptic reflex enhancement. In this preparation and for this pair of compounds, anesthetic properties are related to blockade of transmission at glutamate synapses, with a small component of GABAA enhancement. Monosynaptic reflex increase may be related to the non-anesthetic cyclobutane's convulsant and anti-anesthetic properties.
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PMID:Correlates of anesthetic properties in isolated spinal cord: cyclobutanes. 769 84

It is known that tachykinins (substance P, neurokinin A) participate in the excitatory neural pathways subserving peristaltic motor activity in the intestine. The aim of the present study was to elucidate the types of tachykinin receptor (NK-1 or NK-2) involved in peristalsis by the use of receptor subtype-selective antagonists. Peristaltic motility in isolated segments of the guinea-pig ileum was induced by pumping fluid into the oral end of the intestinal segment. By way of the intraluminal pressure the compliance of the intestinal wall during the preparatory phase and the pressure threshold to trigger the emptying phase of peristalsis were recorded. The tachykinin antagonists were used at concentrations that were at least 30 times in excess of the equilibrium dissociation constants which had previously been evaluated with receptor subtype-selective agonists on the guinea-pig ileum circular muscle. The NK-1 selective antagonist CP-96,345 (0.3 microM) had a slight stimulant influence on peristalsis, whereas the NK-2 selective antagonists MEN-10,376 (10 microM), GR-94,800 (0.3 microM) and SR-48,968 (0.1 microM) led to a small inhibition of motor activity. However, when given after exposure of the ileum to a threshold concentration of atropine (5-20 nM) causing little depression of peristalsis, the tachykinin NK-2 receptor antagonists invariably abolished peristalsis. This synergistic interaction was not seen when SR-48,968 was administered after the ileal segments had been exposed to concentrations of hexamethonium, isoproterenol or calcitonin gene-related peptide that by themselves caused a slight inhibition of peristalsis only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synergistic role of muscarinic acetylcholine and tachykinin NK-2 receptors in intestinal peristalsis. 817 May 3

We have examined the effects of intrathecal (i.t.) galanin message-associated peptide (GMAP), the C-terminal flanking peptide in the galanin (GAL) precursor protein, which is produced in equimolar quantities with galanin and which is upregulated upon axotomy, on the spinal nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats. I.t. GMAP elicited a moderate facilitation of the flexor reflex. No depression of baseline flexor reflex was observed with any dose of GMAP. The facilitation of the flexor reflex induced by conditioning stimulation (CS) of cutaneous C-afferents was dose-dependently blocked by GMAP. The reflex facilitatory effect of exogenously applied substance P (SP), one of the endogenous modulators of reflex hyperexicitability following C-fiber CS, was only blocked by GMAP at a relatively high dose. I.t. GMAP did not antagonize the reflex facilitatory effect of vasoactive intestinal peptide and did not potentiate the reflex depressive effect of i.t. morphine or clonidine. Finally, 1 micrograms i.t. GMAP did not influence spinal cord blood flow whereas 10 micrograms GMAP induced a transient decrease in spinal cord blood flow in some experiments. The ability of GMAP to block the increase in spinal cord excitability following repetitive C-fiber stimulation may be through a presynaptic action. Although some of the effects of GMAP were similar to galanin, distinct differences were found, particularly in interaction with other excitatory and inhibitory agents. It is possible that GMAP exerts its action in the spinal cord through its own specific receptor. GMAP may act similarly to GAL in some, but not all pharmacological functions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of intrathecal galanin message-associated peptide (GMAP) on the flexor reflex in rats. 857 Aug 56

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