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. 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

Experiments were performed to test several predictions of the hypothesis that activity pattern-dependent changes in intracellular free calcium concentration ([Ca2+]i) might play a role in the translation of altered patterns of neuronal activity into changes in neurotransmitter gene expression. It was shown that (1) the Ca2+ channel blocker cadmium prevented depolarization-induced preprotachykinin-I (PPT-I) gene repression in rat sympathetic neurons; (2) the magnitudes of transient rises in [Ca2+]i were dependent upon the pattern in which a fixed number of depolarizing stimuli were delivered; and (3) stimulation at 10 Hz for 24 h did not repress PPT-I mRNA, while the same number of pulses delivered in 0.2 s bursts of 50 Hz caused a highly significant reduction to 30 +/- 2.5% of control levels.
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PMID:Regulation of intracellular calcium and preprotachykinin neurotransmitter precursor gene expression by patterned electrical stimulation in rat sympathetic neurons. 775 90

The mechanism of tachykinin-induced excitation was studied in isolated colonic muscle cells and intact muscle strips. In whole cell voltage-clamp studies performed at 33 degrees C, neurokinin A (NKA) and substance P (SP) reduced L-type Ca2+ current. NKA and SP activated a cationic current that reversed near 0 mV. This current (INKA or ISP, respectively) had properties similar to the acetylcholine (ACh)-activated nonselective cation conductance (IACh), activated by muscarinic stimulation in other gastrointestinal smooth muscle cells. INKA and ISP were decreased when external Na+ was reduced. In contrast to IACh, INKA and ISP were not facilitated by increases in internal Ca2+, but little or no current was activated by these peptides when extracellular Ca2+ was low. INKA (10(-7) M) and ISP (10(-5) M) were blocked by Cd2+ (5 x 10(-4) M), quinine (10(-3) M), and the tachykinin-receptor antagonist [D-Pro2,D-Trp7,9]SP (10(-5) M). Current clamp recordings and intracellular recordings of intact tissues showed that NKA and SP depolarized the cell membrane, which is consistent with the activation of a nonselective cation conductance. These data suggest that a primary mechanism of the tachykinins is to activate a nonselective cation conductance that leads to depolarization. The increase in Ca2+ entry due to tachykinin stimulation appears to be secondary to the activation of the nonselective cation conductance.
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PMID:Tachykinins activate nonselective cation currents in canine colonic myocytes. 857 68

Intracellular recordings were performed on isolated rat DRG neurons to investigate the changes in the membrane potential in response to substance P and the involved ionic mechanisms. The resting membrane potential examined was -58.9 +/- 8.2 mV (X +/- SE) (n = 81). The conduction velocities estimated were: 20.4 +/- 4.8 m/s (X +/- SE) ranging from 14.1 to 28.7 m/s (47/60) in type A(alpha beta) cell, 9.8 +/- 5.2 m/s (X +/- SE) ranging from 1.2 to 13.7 m/s (13/60 in type A(delta) and type C cell. In majority of the neurons bath application of SP (10(-7) - 3 x 10(-4) mol/L) induced marked membrane potential depolarization (56/60). The membrane conductance increased 24.6% in average from control value of 2.72 x 10(-8) S during SP-induced depolarization (n = 3). The reversal potential was between +40 - %50 mV (n = 3). When NaCl in BSS was substituted with choline chloride or containing TTX (10(-5) mol/L), the amplitude of SP-induced depolarization attenuated markedly but not incompletion eventually. When high (20 mmol/L) and low (0 mmol/L) Ca2+ BSS was used, the amplitude of SP-induced depolarization increased and decreased respectively. However, when BSS containing 10(-4) mol/L Cd2+ or 10(-2) mol/L TEA was used SP-induced depolarization was reduced. The above results indicate that SP-induced depolarization involves a rather multiple changes in ionic conductance.
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PMID:[Effect of substance P on the somatic membrane of rat DRG neurons]. 875 84

Neurons in the superior vagal (jugular) ganglion relay afferent information from thoracic visceral organs and may be important in inflammatory processes due to the peripheral release of bioactive neuropeptides such as substance P. We characterized the excitable properties and underlying voltage-gated Na+ (INa) and K+ (IKv) currents in acutely dissociated guinea pig jugular ganglion neurons with microelectrode and whole-cell patch-clamp recording techniques. Current clamp recordings revealed a resting potential of approx. -55 mV and input resistance of approx. 100 M ohms. Brief depolarizing steps evoked an overshooting action potential (approx. 2 ms duration), fast (< 20 ms duration) afterhyperpolarization (AHPF) sequence in all neurons, followed by a slow (> 1 s) Cd(2+)-sensitive afterhyperpolarization (AHPS) in 45% of the neurons. The AHPS was implicated in limiting repetitive action potential firing during maintained depolarizing steps. The action potential in 15/17 neurons, and a major component of the whole cell INa in 13/13 neurons were insensitive to TTX (1-10 microM), indicating that jugular neurons express predominantly a TTX-resistant type of INa. Cd2+ (200 microM) did not affect action potential repolarization, while tetraethylammonium (TEA; 10 mM) in the presence of Cd2+ markedly prolonged action potential repolarization, and blocked the AHPF in 11/11 neurons. This suggested that the action potential repolarization and the AHPF are mediated by IKv, with little contribution by Ca(2+)-dependent IK (IK(Ca)). Whole cell IKv activated rapidly (tau < 1.5 ms), and inactivated variably over a time period of seconds. IKv activation and inactivation voltage dependencies and TEA sensitivity were compatible with its availability during the action potential and AHPF. Only 1/26 neurons exhibited current with the rapid inactivation kinetics and voltage-dependencies characteristic of classic IA-type current. These results highlight differences in the properties of jugular neurons (e.g., deficiency of rapid IA, and lack of a TTX-sensitive subpopulation), relative to those known for other visceral and somatic afferents, and thus provide a basis for further functional studies.
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PMID:Excitable properties and underlying Na+ and K+ currents in neurons from the guinea-pig jugular ganglion. 878 83

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

1. Membrane currents were recorded by a patch clamp technique in guinea-pig tracheal myocytes, using the whole cell mode with Cs(+) internal solution. 2. Both neurokinin A (NKA, 1 mu M) and caffeine (10 mM) evoked Ca(2+)-activated Cl- currents (I[Cl(Ca)]) transiently. In Ca(2+)-free bathing solution, the first application of NKA or caffeine elicited I[Cl(Ca)] but the second application of these substances failed to activate it. In addition, pretreatment with ryanodine in the presence of caffeine abolished the response to both NKA and caffeine whilst heparin (200 mu g ml(-1)) only blocked the NKA-induced response. I[Cl(Ca)] was also elicited by inositol 1,4,5-trisphosphate (IP(3)). 3. Command voltage pulses positive to 0 mV from a holding potential of -60 mV activated the voltage-dependent L-type Ca2+ current (I(Ca,L)) and late outward current. Upon repolarization to the holding potential, slowly decaying inward tail currents were recorded. The outward current during the depolarizing pulses and the inward tail current were enhanced by Bay K 8644, but completely blocked by Cd2+ or nifedipine. Replacement of external Ca2+ with Ba2+, removal of Ca2+ from the bath solution, or inclusion of EGTA (5 mM) in the patch pipette, also led to abolition of these currents, indicating that they were Ca2+ dependent, and that Ca2+ influx due to I(Ca,L) activated the currents. 4. When [Cl(-)](O) or [Cl(-)](i) was changed, the reversal potential (E(rev)) of the Ca2+-activated currents shifted, thus behaving like a Cl(-)-selective ion channel as predicted by the Nernst equation. DIDS (1 mM) completely abolished the currents, also suggesting that they were I[Cl(Ca)]. 5. NKA (1 mu M) and caffeine (30 mM) transiently activated I[Cl(Ca)], and after that both agents markedly reduced I[Cl(Ca)] induced by I(Ca,L). This is probably due to sarcoplasmic reticulum (SR) Ca2+ release induced by NKA or caffeine, followed by inhibition of the Ca(2+)-induced Ca2+ release from the SR. 6. The present results indicate that I[Cl(Ca)] can be activated by SR Ca2+ release due to NKA or caffeine (through IP(3) or ryanodine receptors) as well as by Ca2+ influx due to I(Ca,L). It also suggests that activation of I[Cl(Ca)] by NKA may be mediated by the production of IP(3), which releases Ca2+ from the SR.
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PMID:Neurokinin A and Ca2+ current induce Ca(2+)-activated Cl(-) currents in guinea-pig tracheal myocytes. 901 36

Substance P, a putative peptide neurotransmitter contained in primary sensory neurons, is suggested to play a major role in nociceptive transmission. In the present study, the existence of substance P autoreceptor in dorsal root ganglion neurons was identified with a method we developed recently and substance P-activated inward current in the dorsal root ganglion neurons and its ionic mechanism were also explored preliminarily. The majority of the cells examined (68/76, 89.5%) were sensitive to external application of substance P (0.01-10 microM) with a concentration-dependent inward current. This current was found to result from the opening of nonselective ion channel, preferring the Na+ channel. The substance P-activated current can be suppressed by Cd2+ (0.05 microM), which suggested Ca2+ may also be involved. Soon after the neurons had been identified to be endowed with substance P receptor with whole-cell patch-clamp technique, 17 cells were chosen for immunocytochemical staining to detect substance P-immunoreactivity. Seven neurons which were classified into small and intermediate size were found to reveal substance P-immunoreactivity. Using this method we have identified the existence of substance P autoreceptor in rat DRG neurons.
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PMID:Evidence for the existence of substance P autoreceptor in the membrane of rat dorsal root ganglion neurons. 947 9

Neuropeptides are known to modulate the excitability of mammalian sympathetic neurons by their actions on various types of K+ and Ca2+ channels. We used whole cell patch-clamp recording methods to study the actions of substance P (SP) on dissociated adult guinea pig stellate ganglion (SG) neurons. Under current-clamp conditions, SG neurons exhibited overshooting action potentials followed by afterhyperpolarizations (AHP). The K+ channel blocker tetraethylammonium (1 mM), the Ca2+ channel blocker Cd2+ (0.1-0.2 mM), and SP (500 nM) depolarized SG neurons, decreased the AHP amplitude, and increased the action potential duration. In the presence of Cd2+, the effect of SP on membrane potential and AHP was reduced. Under voltage-clamp conditions, several different K+ currents were observed, including a transient outward K+ conductance and a delayed rectifier outward K+ current (IK) consisting of Ca(2+)-sensitive [IK(Ca)] and Ca(2+)-insensitive components. SP (500 nM) inhibited IK. Pretreatment with Cd2+ (20-200 microM) or the high-voltage-activated Ca2+ channel blocker omega-conotoxin (10 microM) blocked SP's inhibitory effects on IK. This suggests that SP reduces IK primarily through the inhibition of IK(Ca) and that this may occur, in part, via a reduction of Ca2+ influx through voltage-dependent Ca2+ channels. SP's actions on IK were mediated by a pertussis toxin-insensitive G protein(s) coupled to NK1 tachykinin receptors. Furthermore, we have confirmed that 500 nM SP reduced an inward Cd(2+)- and omega-conotoxin-sensitive Ba2+ current in SG neurons. Thus the actions of SP on IK(Ca) may be due in part to a reduction in Ca2+ influx occurring via N-type Ca2+ channels. This study presents the first description of ionic currents in mammalian SG neurons and demonstrates that SP may modulate excitability in SG neurons via inhibitory actions on K+ and Ca2+ currents.
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PMID:Actions of substance P on membrane potential and ionic currents in guinea pig stellate ganglion neurons. 957 85

The effects of substance P (SP) on whole cell currents were studied in neurons of the medial olivocochlear efferent system (MOCS) in the ventral nucleus of the trapezoid body (VNTB) of brain stem slices from neonatal rats. Each neuron was identified by retrograde labeling with Fast Blue injected into the cochlea. Bath application of SP (0.1-10 microM) reversibly induced an apparent inward current in 49 of 63 labeled neurons when voltage clamped at near resting voltages. This apparent inward current was consistent with the SP-induced membrane depolarization observed in current-clamp mode. The SP-induced change in current was dose dependent with a half-maximal response dose of 200 nM. It was mimicked by [Cys3,6, Tyr8, Pro9]-SP, a neurokinin (NK1) receptor selective agonist, whereas [Succinyl-Asp6, MePhe8]-SP 6-11 (Senktide), a NK3 receptor agonist, had no detectable effect. The SP effect was not blocked by 10(-6) M tetrodotoxin (TTX) and persisted when the perfusate contained 30 mM tetraethylammonium (TEA) or 100 microM Cd2+ or was in a 0-Ca solution. In a TTX-containing solution, SP caused a voltage-dependent decrease of membrane conductance, and the SP-evoked current reversed at a potential at around -105 mV. The predicted K+ equilibrium potential was -93.8 mV under the experimental conditions. The SP-induced inward current was attenuated by 66% when the perfusate contained 3 mM Cs+. We conclude that the apparent inward current is partly caused by SP decreasing an outward current normally maintained by the inward rectifier K+ channels in these cells. In the presence of Cs solution in the recording pipette and with a perfusate containing 3 mM Cs+, 0.1 mM Cd2+ and 10(-6) M TTX, a residual SP-induced inward current was observed at test voltages ranging from -120 to 40 mV. This subcomponent reversed its polarity at approximately 20 mV. This inward current was reduced substantially (but not abolished) when all NaCl in the external solution was replaced by TEA-Cl. The results indicate that SP also opens an unknown cation channel, which the available data suggests may be relatively nonselective. The results suggest that MOCS neurons are subject to modulation by SP, which depolarizes the cell membrane by decreasing the activity of inward rectifier K+ channels as well as concurrently activating a separate cation conductance. It also was found that in MOCS neurons responsive to both SP and norepinephrine, the norepinephrine effect was abolished by TTX, suggesting that an interneuronal population excited by norepinephrine converges selectively onto SP-sensitive MOCS neurons in the VNTB.
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PMID:Substance P-induced inward current in identified auditory efferent neurons in rat brain stem slices. 965 43


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