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

Intracellular recordings were made from isolated left or right stellate ganglia of Wistar rats and the morphology of neurones studied after intracellular injection of hexammine cobaltic chloride or back-filling from the post-ganglionic nerve with cobalt lysine complex. The experiments attempted to identify the location, electrophysiological properties, morphology and chemosensitivity of putative cardiac neurones in the ganglion. These were identified by antidromic activation of the axon in a cardiac nerve and compared with neurones projecting towards the brachial plexus (non-cardiac neurones). Putative cardiac neurones were localized in the ganglion around the postganglionic nerve entry zone and showed considerable morphological diversity. They had complex dendritic trees with, on average, seven dendrites. They included both phasic and tonic neurones and were depolarized by muscarinic agonists, angiotensin and substance P; they invariably had a synaptic input from the sympathetic trunk and from a T1 or T2 ramus and, in 16% of cells, from a cardiac nerve. Non-cardiac neurones were more widely scattered through the stellate ganglion but were not clearly different in morphology, resting membrane potential or the proportion of phasic and tonic cells from putative cardiac neurones. They also showed depolarizing responses to muscarinic agonists, angiotensin and substance P. Angiotensin responses of stellate ganglion cells were blocked by the peptide antagonist, saralasin (1 microM).
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PMID:Properties of putative cardiac and non-cardiac neurones in the rat stellate ganglion. 751 22

The contractile effects of 5-hydroxytryptamine (5-HT) and influences of several kinds of divalent cations were investigated on longitudinal muscle strips of the guinea-pig isolated distal colon. 5-HT (10 nM-10 microM) produced phasic contractions which were partially inhibited by atropine (1 microM) and markedly inhibited by tetrodotoxin (1 microM), indicating that 5-HT acts mainly on the myenteric plexus and releases transmitters to cause contraction of the longitudinal muscle. The contractile response to 5-HT (3 microM) was almost completely inhibited by spantide (10 microM), a substance P antagonist, in the presence of atropine (1 microM), while spantide alone did not block 5-HT-induced contraction. Of several divalent cations including Cd2+, Co2+, Mg2+, Mn2+, Ni2+, Sr2+ and Zn2+, Cd2+ ions (10 mu-100 microM), which block L- and N-type Ca2+ channels, were most effective inhibitor of the 5-HT-induced contractions. While Sr2+ and Co2+ at a concentration of 100 microM did not have a significant effect. The order effectiveness of inhibition was Cd2+ >> Mn2+ > Mg2+ = Ni2+ = Zn2+. Bay K 8644 (1 microM), a L-type Ca2+ channel activator, did not influence the contractile response of the longitudinal muscle strip to 5-HT (3 microM). The present results suggest that 5-HT may mainly act on N-type Ca2+ channels in the myenteric neurones and cause the release of at least acetylcholine and substance P to induce contractions of the longitudinal muscle in the guinea-pig distal colon.
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PMID:Contractile responses of longitudinal muscle strip to 5-HT and influences of divalent cations in the guinea-pig isolated colon. 751 8

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

1. Intracellular microelectrode and whole-cell patch-clamp recordings were obtained from adult guinea pig celiac ganglion neurons grown in tissue culture for 7-14 days. Over 90% of neurons showed phasic-type action-potential discharge with the use of either type of recording electrode; they stained immunohistochemically for catecholamines, tyrosine hydroxylase, and neuropeptide Y. Input resistance (140 M omega) and action-potential amplitude (103 mV) were significantly greater with whole-cell than with microelectrode recordings, but other passive electrical properties were similar. 2. Five potassium currents were characterized: an apamin-sensitive after hyperpolarizing current (IAHP), an apamin and tetraethylammonium-insensitive slow IAHP, an M-like current, a transient outward IA current, and a delayed rectifier IK current. A hyperpolarization-activated cationic Ih current was also present. The first three currents were not observed with whole-cell recordings. 3. Cadmium (200 microM), cobalt (1 mM), lanthanum (30 microM), or a low calcium/high magnesium solution blocked both IAHPS and the M-like current; barium (1 mM) also blocked these currents. 4. Kinetics of the M-like current were best described by a double exponential fit to deactivating tail currents with time constants of 50 and 390 ms at -50 mV. The apamin-sensitive and slow IAHP decayed exponentially with time constants of 145 ms and 3.5 s, respectively. There was no correlation between occurrence of M-like current (95% of neurons) and slow IAHP (40% of neurons), nor any correlation between magnitude of M-like current and IAHP in those cells exhibiting both currents. 5. Muscarine and substance P (SP) caused depolarizations or inward currents (under voltage clamp) at the resting potential (-55 mV) associated with a decreased membrane conductance. The slow IAHP and the M-like current, but not the apamin-sensitive IAHP nor the IA, were blocked by muscarine and SP (IC50 3 microM and 100 nM, respectively). Muscarine and SP also decreased a "leak" potassium current. 6. We conclude that celiac neurons express two calcium-dependent IAHP currents and a calcium-dependent M-current; these are seen by fine-tipped intracellular microelectrodes but not by whole-cell patch electrodes. These currents are not required for spike frequency accommodation. Muscarine and SP reduce these currents, as well as voltage-independent leakage potassium current.
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PMID:Potassium currents and their modulation by muscarine and substance P in neuronal cultures from adult guinea pig celiac ganglia. 768 76

1. Intracellular recordings were made from submucosal neurones and single-electrode voltage-clamp methods were used to record membrane currents. The actions of substance P (SP), 5-hydroxytryptamine (5-HT), muscarine, vasoactive intestinal polypeptide (VIP), forskolin and nerve stimulation were studied. 2. Substance P, 5-HT (in the presence of 5-HT3 receptor antagonists), muscarine, VIP, forskolin and slow excitatory synaptic transmission all produced identical responses: an inward current associated with a membrane conductance decrease at the resting potential. The actions of any one occluded the actions of any other and all responses were pertussis-toxin insensitive. 3. These agonists produced a voltage-independent decrease in a 'leak' potassium conductance between -40 and -120 mV in 14% of neurones. 4. These agonists decreased a voltage-dependent, calcium-activated potassium conductance between -40 and -80 mV in all other (86%) neurones. The agonists still evoked an inward current without apparent conductance change at potentials between -90 and -130 mV. 5. In a low calcium solution containing cobalt or cadmium, the agonists produced an inward current associated with a conductance increase from -40 to -120 mV. Ion replacement studies indicated this current was due to an increase in a cation-selective (mainly sodium) conductance. 6. The agonists also reduced the inwardly rectifying potassium current that is activated by somatostatin and alpha 2-adrenoceptor agonists in these neurones. The agonists did not alter the inwardly rectifying potassium current that is present in these neurones in the absence of somatostatin or alpha 2-agonists. 7. Thus, SP, 5-HT, muscarine, VIP and the release of slow excitatory transmitters all appear to act through a common intracellular transduction pathway, an increase in adenylate cyclase. This results in an activation of a sodium-selective cation current and an inhibition of three distinct potassium conductances: the background potassium conductance, the calcium-activated potassium conductance and the inwardly rectifying potassium conductance activated by somatostatin and alpha 2-adrenoceptor agonists.
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PMID:Common ionic mechanisms of excitation by substance P and other transmitters in guinea-pig submucosal neurones. 768 94

We have investigated the interaction of fluorescent peptide ligands with the G protein-coupled receptor NK2 using novel spectrofluorometric approaches. Several heptapeptide antagonists of structure PhCO-Xaa-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 were labelled on position 1 (Xaa) with the environment-sensitive nitrobenzoxadiazole (NBD) probe, differing only in the length of the spacer between the NBD group and the peptide. Upon binding of the labelled antagonist to NK2 receptors stably expressed in Chinese hamster ovary (CHO) cells, an increase in NBD fluorescence was observed when the spacer length was less than 10 A. Collisional quenching experiments using iodide and Co2+ ions were performed to define the accessibility of the NBD group on bound ligands to the solvent. By comparing ligands with spacer arms of varying lengths, we found that the binding pocket is buried at a depth of 5-10 A. In contrast, N-terminally NBD-labelled agonists, decapeptide neurokinin A (NKA) or heptapeptide Nle10-NKA[4-10], bound to the NK2 receptor were accessible to the solvent. Binding of fluorescent ligands to the NK2 receptor was accompanied by an enhancement in the fluorescence anisotropy. The changes in fluorescence properties were used to determine the kinetic parameters of antagonist binding and dissociation. These results indicate that the binding site on the NK2 receptor for the amino-terminal end of the heptapeptide antagonists is buried in the hydrophobic pocket of the receptor protein and clearly distinct from the binding site for the amino-terminal end of agonists, which is accessible to the solvent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Probing the binding domain of the NK2 receptor with fluorescent ligands: evidence that heptapeptide agonists and antagonists bind differently. 769 62

1. Tetanic stimulation of lamprey sensory dorsal cells resulted in a posttetanic hyperpolarization (PTH). The amplitude and duration of the PTH were dependent on the stimulus duration and frequency. The PTH was not reversed at membrane potentials negative to -100 mV, whereas the afterhyperpolarization following single action potentials reversed at approximately -85 mV. There was also a biphasic effect on the input resistance during the PTH, with an early reduction that recovered to control before the PTH had decayed. 2. The amplitude and duration of the PTH were increased in Ringer solution containing tetraethylammonium and 4-aminopyridine, both of which broadened single action potentials, but were reduced after intracellular injection of Cs+. Ca(2+)-free Ringer solution, Cd2+, and Co2+ also reduced the PTH, suggesting the involvement of a Ca(2+)-dependent K+ conductance. However, the PTH was not reduced in Ba2+ Ringer solution, or by the Ca(2+)-dependent K+ channel antagonists apamin and charybdotoxin. 3. The cardiac glycoside ouabain reduced the amplitude and duration of the PTH, as did substitution of Na+ with choline or Li+. K(+)-free Ringer solution also reduced the PTH, whereas high-K+ Ringer solution had more variable effects. The amplitude and duration of the PTH were also dependent on temperature. These results support the involvement of an ouabain-sensitive Na-K pump in the PTH. 4. The PTH was reduced by the tachykinins substance P and physalaemin, and by 5-hydroxytryptamine, which blocks apamin-sensitive Ca(2+)-dependent K+ channels in the lamprey. However, gamma-aminobutyric acid, which has been reported to reduce a Ca(2+)-dependent K+ conductance in the dorsal cells, did not reduce the PTH. 5. These results suggest that a Ca(2+)-dependent K+ conductance and an Na-K electrogenic pump underlie the PTH. The PTH reduces the excitability of the dorsal cells, suggesting that it may act as a mechanism to gate sensory information entering the spinal cord.
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PMID:Electrogenic pump and a Ca(2+)- dependent K+ conductance contribute to a posttetanic hyperpolarization in lamprey sensory neurons. 883 42

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

1. The whole-cell patch-clamp technique was used to investigate the actions of substance P and other agonists at neurokinin (NK) receptors on voltage-gated K+ and Ca+ channel currents in undifferentiated mouse neuroblastoma x rat glioma NG 108-15 cells. 2. Both substance P (0.3-30 microM) and the NK1 receptor selective agonist GR73632 (10 nM-10 microM) caused concentration-dependent inhibition of K+ currents. GR64349 and senktide (agonists at NK2 and NK3 receptors respectively) also inhibited K+ currents, but only at concentrations which were several orders of magnitude greater than GR73632, suggesting that current inhibition was mediated via NK1 receptors. 3. Substance P and GR73632 were without effect on residual K+ currents recorded in the presence of extracellular Co2+ (4 mM) to abolish the Ca(2+)-sensitive component (IKca) of the K+ current. Ca2+ channel currents, recorded with either Ba2+ or Ca2+ as charge carrier, were unaffected by NK1, NK2 and NK3 receptor ligands. 4. Iontophoretic application of GR73632 produced a current-dependent reduction of K+ currents. In the presence of the non-peptide NK1 antagonists, CP-99,994 and RP67580, and the peptide antagonist, GR82334, the current-response relationship was reversibly shifted to the right. This indicates that the response is mediated by NK1 receptors. 5. Our results indicate that activation of NK1 receptors leads to the selective inhibition of IKca in undifferentiated NG 108-15 cells.
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PMID:Inhibition of Ca(2+)-sensitive K+ currents in NG 108-15 cells by substance P and related tachykinins. 888 15

The superficial dorsal horn is a major site of termination of nociceptive primary afferents. Fast excitatory synaptic transmission in this region is mediated mainly by release of glutamate onto postsynaptic AMPA and NMDA receptors. NMDA receptors are known to be Ca2+-permeable and to provide synaptically localized Ca2+ signals that mediate short-term and long-term changes in synaptic strength. Less well known is a subpopulation of AMPA receptors that is Ca2+-permeable and has been shown to be synaptically localized on dorsal horn neurons in culture (Gu et al., 1996) and expressed by dorsal horn neurons in situ (Nagy et al., 1994; Engelman et al., 1997). We used kainate-induced cobalt uptake as a functional marker of neurons expressing Ca2+-permeable AMPA receptors and combined this with markers of nociceptive primary afferents in the postnatal rat dorsal horn. We have shown that cobalt-positive neurons are located in lamina I and outer lamina II, a region strongly innervated by nociceptors. These cobalt-positive neurons colocalize with afferents labeled by LD2, and with the most dorsal region of capsaicin-sensitive and IB4- and LA4-positive afferents. In contrast, inner lamina II has a sparser distribution of cobalt-positive neurons. Some lamina I neurons expressing the NK1 receptor, the receptor for substance P, are also cobalt positive. These neurons are likely to be projection neurons in the nociceptive pathway. On the basis of all of these observations, we propose that Ca2+-permeable AMPA receptors are localized to mediate transmission of nociceptive information.
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PMID:The distribution of neurons expressing calcium-permeable AMPA receptors in the superficial laminae of the spinal cord dorsal horn. 1006 61


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