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)

Beta-(4-chlorophenyl)-GABA (Baclofen, Lioresal) antagonized the excitant actions of acetylcholine and substance P to comparable extents. L-glutamate-induced excitation was affected to a lesser extent. These findings do not support the suggestion that beta-(4-chlorophenyl)-GABA is a specific substance P antagonist.
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PMID:Is beta-(4-chlorophenyl)-GABA a specific antagonist of substance P on cerebral cortical neurons? 127 5

1. The role of gamma-aminobutyric acid (GABA) as an inhibitory transmitter in the central nervous system is well documented. Recently, GABAA and GABAB receptors have been identified in the peripheral nervous system, notably on primary afferent neurones (PAN). We have utilised a multi-superfusion system to investigate the effect of selective GABA receptor agonists and antagonists on the release of substance P (SP) from the rat trachea in vitro. 2. GABA (1-100 microM) did not affect spontaneous release of SP-like immunoreactivity (LI) but caused dose-related inhibition of calcium-dependent potassium (60 mM)-stimulated SP-LI release. The greatest inhibition of 77.7 +/- 18.8% was observed at 100 microM. 3. The inhibitory effect of GABA was mimicked by the GABAB receptor agonist, (+/-)-baclofen (1-100 microM), but not the GABAA receptor agonist, 3-amino-1-propane-sulphonic acid (3-APS, 1-100 microM). Baclofen (100 microM) had no effect on SP-LI release stimulated by capsaicin (1 microM). 4. The inhibitory effect of baclofen (30 microM) was significantly reduced by prior and concomitant exposure to the GABAB receptor antagonist, phacolofen (100 microM) but not the GABAA receptor antagonist, bicuculline (10 microM). Neither antagonist, alone, affected spontaneous or potassium-stimulated SP-LI release. 5. We conclude that activation of pre-synaptic GABAB receptors on the peripheral termini of PANs in the rat trachea inhibits SP-LI release and suggest that GABAB receptor agonists may be of value in the therapeutic treatment of asthma.
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PMID:GABAB receptor modulation of the release of substance P from capsaicin-sensitive neurones in the rat trachea in vitro. 171 5

The spinal regulation of cardiovascular sympathetic preganglionic neurons by substance P (SP) and gamma-aminobutyric acid (GABA) was investigated in conscious rats. Intrathecal injection at the T-9 spinal level of bicuculline, a GABAA receptor antagonist, evoked increases in mean arterial pressure (MAP) and heart rate (HR) which were maximal at 5.0 and 0.5 nmol, respectively. Phaclofen, a GABAB receptor antagonist, produced no cardiovascular changes up to 2 mumol while 10 mumol evoked a rise in MAP and HR. Muscimol, a GABAA receptor agonist, produced a decrease in MAP which was maximal at 5.0 nmol and had no effect on HR. Baclofen, a GABAB receptor agonist, was without cardiovascular effects up to 5.0 nmol, while 50 and 100 nmol evoked a fall in MAP and HR. The pressor response to SP (16.25 nmol, T-9) was antagonised by 0.5-50 nmol muscimol or baclofen in a dose-related manner and the pressor response to SP was still inhibited by 40 nmol GABA in capsaicin-treated animals. However, when SP was injected at T-2, the rise in both MAP and HR was blocked by 50 nmol baclofen. Similarly, 50 nmol muscimol blocked the rise in both MAP and HR induced by 15 nmol thyrotropin-releasing hormone. In contrast, 50 nmol glycine failed to alter the cardiovascular response to SP co-injected either at T-9 or T-2. Baclofen was found to reduce significantly the basal release of epinephrine when injected at the T-9 level. These results provide pharmacological evidence for a possible tonic GABAergic inhibitory input onto cardiovascular sympathetic preganglionic neurons mediated by GABAA and GABAB receptors.
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PMID:Regulation of cardiovascular sympathetic neurons by substance P and gamma-aminobutyric acid in the rat spinal cord. 172 52

We report a nociceptive test involving peripheral irritation which produces behavior similar to that elicited by intrathecally injected substance P. Intradermal hypertonic saline injected to the lower abdominal area produced quantifiable behavior in mice. The behavior consisted of licking, biting and scratching directed to the location of i.d. injection, and was dose-dependent with respect to the concentration and volume of saline. Intrathecally administered (D-Pro2, D-Trp7,9)-SP, a substance P antagonist, dose-dependently blocked the behaviors induced by intrathecally administered substance P as well as those induced by intradermally injected hypertonic saline, indicating a possibly common final pathway at the spinal cord level for the manifestation of both behaviors. Hypertonic saline-induced behavior was blocked completely by morphine and a partial opiate agonist (pentazocine) in a dose-dependent manner, but was not blocked by another partial opiate agonist (nalorphine). The behavior was not blocked by non-steroidal anti-inflammatory agents. This nociceptive test, in conjunction with the substance P-induced behavior test, may allow discrimination between agents acting pre- or post-synaptically in the spinal cord. Baclofen, a GABAB agonist thought to act presynaptically, changed substance P-induced behavior and hypertonic saline-induced behavior in opposite directions.
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PMID:Intradermal hypertonic saline-induced behavior as a nociceptive test in mice. 242 7

The effects of gamma-aminobutyric acid (GABA) and other drugs which interact with GABA receptors were studied on a reflex of slow time course in the spinal cord preparation isolated from the neonatal rat. A single shock to a dorsal root (L3-L5) elicited a stereotyped series of reflexes, consisting of fast and slow components, recorded from the contralateral ventral root of the corresponding segment. The slow component, i.e. the contralateral slow ventral root potential (v.r.p.) had a time-to-peak of 2-5 s and lasted 20-30 s. Bath-application of GABA (5-20 microM) or muscimol (0.05-0.5 microM) caused a decrease in the amplitude of the contralateral slow v.r.p. without producing any change in the d.c. potential recorded from the ventral root. The monosynaptic reflex recorded from the ipsilateral ventral root was not changed by the drugs at these concentrations. Diazepam (0.1-1 microM) potentiated the depolarizing response of the dorsal root to GABA and markedly depressed the contralateral slow v.r.p. Neither the d.c. potential of the ventral root nor the dorsal root was changed by diazepam. The monosynaptic reflex was also unaffected by the drug. Bicuculline (1 microM) suppressed the GABA-induced depolarization recorded from the dorsal root whilst it markedly potentiated the contralateral slow v.r.p. Baclofen at concentrations from 0.01 to 0.1 microM reduced the contralateral slow v.r.p. The inhibitory action of baclofen on the contralateral slow v.r.p. was more marked than on the monosynaptic reflex. 7 The depolarization of the ventral root induced by a brief application of substance P (SP) was depressed by muscimol, diazepam and baclofen, whereas the depolarization was potentiated by bicuculline. 8 The present results suggest that an intraspinal GABAergic inhibitory mechanism plays a role in the modulation of certain slow spinal reflexes. They also support the hypothesis that SP released from certain primary afferent fibres is a neurotransmitter involved in the contralateral slow v.r.p.
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PMID:GABAergic modulation of a substance P-mediated reflex of slow time course in the isolated rat spinal cord. 243 59

1. Evidence suggests that gamma-aminobutyric acid (GABA) and its receptors are present in the peripheral nervous system. We have now investigated the effect of GABA and related substances on non-adrenergic, non-cholinergic (NANC) neurally-evoked bronchoconstriction in the anaesthetised guinea-pig. 2. Bilateral vagal stimulation (5 V, 5 ms, 3 or 5 Hz) for 30 s, after propranolol (1 mg kg-1 i.v.) and atropine (1 mg kg-1 i.v.) evoked a NANC bronchoconstrictor response manifest as a mean tracheal pressure rise of 21.9 +/- 1.04 cmH2O (n = 70). The bronchoconstrictor response was reproducible for any given animal. 3. GABA (10 micrograms-10 mg kg-1 i.v.) did not alter basal tracheal pressure but reduced the NANC bronchoconstrictor response to vagal stimulation in a dose-dependent manner (ED50 = 186 micrograms kg-1 with a maximal inhibition of 74 +/- 3.4% at 10 mg kg-1). Neither the opioid antagonist naloxone (1 mg kg-1 i.v.) nor the alpha-adrenoceptor antagonist phentolamine (2.5 mg kg-1 i.v.) had any significant effect on the inhibitory response produced by GABA (500 micrograms kg-1). 4. GABA-induced inhibition was not antagonised by the GABAA-antagonist bicuculline (2 mg kg-1 i.v.). 5. The GABAB-agonist baclofen (10 micrograms-3 mg kg-1 i.v.) caused a dose-dependent inhibition of the NANC response (ED50 = 100 micrograms kg-1 with a maximal inhibition of 35.5 +/- 2.8% at 3 mg kg-1). The GABAA-agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-C] pyridin-3-ol (THIP), also inhibited the NANC bronchoconstrictor response. However, the dose of THIP required for this effect was high (3 mg kg- ') and the effect ( <10% inhibition) was small. 6. Substance P (SP; 5upgkg-1 or 25pgkg-1), produced a bronchoconstrictor response equivalent to that produced by NANC vagal stimulation. This response was significantly increased by injection of GABA. Baclofen had no significant effect on responses evoked by exogenous SP. 7. We conclude that GABA inhibits the release of transmitter from NANC nerves via an action at GABAB receptors and that GABA might play a role in the regulation of neurogenic responses in the airways.
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PMID:Modulation of non-adrenergic, non-cholinergic neural bronchoconstriction in guinea-pig airways via GABAB-receptors. 247 4

Intrathecal administration of 20 micrograms of substance P induced scratching behavior in most tested rats (80%). Scratching appeared in bouts of short latency and variable duration, intensity and frequency (range 1-60, mean number of scratching bouts in one hour test: 8.93 +/- 1.86). Intrathecal administration of glycine (400 micrograms but not 66 micrograms) significantly decreased the effect of substance P on this behavior. Taurine, in dosages equimolar to glycine, abolished the response to substance P at the high dose level (700 micrograms), but did not significantly affect it at the lower level (120 micrograms). The GABAA agonist, muscimol, abolished the effect of substance P at the 3 micrograms dose level, but the 0.5 microgram dose did not produce a significant effect. Baclofen, a GABAB agonist, was highly effective in significantly reducing the action of SP at 0.9 and 0.15 microgram; only two of 8 rats receiving the low dose of baclofen (0.15 microgram) exhibited scratching. The results suggest that the spinal inhibitory amino acids modulate nociceptive impulses generated by the action of substance P in dorsal horn neurons of the spinothalamic tract.
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PMID:Blockage of substance P-induced scratching behavior in rats by the intrathecal administration of inhibitory amino acid agonists. 248 79

Both directly acting (GABAA and GABAB agonists) and indirectly acting GABAergic agents (GABA uptake inhibitors and GABA-transaminase inhibitors) produce analgesia in a variety of animal test systems. Analgesia produced by GABAA agonists is probably due to a supraspinal action, although spinal sites may also play a role. GABAA agonist analgesia is insensitive to naloxone, bicuculline, picrotoxin and haloperidol, but is blocked by atropine, scopolamine and yohimbine suggesting a critical role for central cholinergic and noradrenergic pathways in this action. The lack of blockade by the GABAA antagonist bicuculline is difficult to explain. Both bicuculline and picrotoxin have intrinsic analgesia actions which may not necessarily be mediated by GABA receptors. The GABAB agonist baclofen produces analgesia by actions at both spinal and supraspinal sites. Baclofen analgesia is insensitive to naloxone, bicuculline and picrotoxin, and blockade by cholinergic antagonists occurs only under limited conditions. Catecholamines are important mediators of baclofen analgesia because analgesia is potentiated by reserpine, alpha-methyl-p-tyrosine, phentolamine, ergotamine, haloperidol and chlorpromazine. A role for serotonergic mechanisms is less well defined. Methylxanthines, which produce a clonidine-sensitive increase in noradrenaline (NA) turnover, increase baclofen analgesia by a clonidine-sensitive mechanism. Both ascending and descending NA pathways are implicated in the action of baclofen because dorsal bundle lesions, intrathecal 6-hydroxydopamine and medullary A1 lesions markedly decrease baclofen analgesia. However, simultaneous depletion of NA in ascending and descending pathways by locus coeruleus lesions potentiates baclofen analgesia suggesting a functionally important interaction between the two aspects. Baclofen analgesia within the spinal cord may be mediated by a distinct baclofen receptor because GABA does not mimic the effect of baclofen and the rank order of potency both of close structural analogs of baclofen as well as antagonists differs for analgesia and GABAB systems. The spinal mechanism may involve an interaction with substance P (SP) because SP blocks baclofen analgesia, and desensitization to SP alters the spinal analgesic effect of baclofen. GABA uptake inhibitors produce analgesia which is similar to that produced by GABAA agonists because it is blocked by atropine, scopolamine and yohimbine. Analgesia produced by GABA-transaminase inhibitors is similar to that produced by GABAA agonists because it can be blocked by atropine, but it is potentiated by haloperidol while THIP analgesia is not.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:GABAergic mechanisms of analgesia: an update. 303 1

GABAergic mechanisms appear to be involved in antinociceptive processes. Generally, peripheral administration of GABAergic agents increases the antinociceptive effect of morphine, but central administration inhibits this effect, suggesting that multiple interactions may occur. GABAergic agents also can produce antinociception directly. Muscimol and THIP (GABAA agonists) act at supraspinal sites to produce antinociception, but do not appear to interact with bicuculline sensitive receptors. Baclofen (a GABAB agonist) acts at both supraspinal and spinal sites. Supraspinal mechanisms include inhibition of ascending noradrenergic and dopaminergic pathways but activation of descending noradrenergic pathways. The spinal mechanism may involve postsynaptic inhibition of the effect of substance P. D-Baclofen is an antagonist at spinal baclofen receptors. Antinociception produced by inhibitors of GABA-transaminase is not reduced by bicuculline in most studies, while manipulations which increase the antinociceptive effect of baclofen do not alter or block the effect of GABA-transaminase inhibitors. An understanding of the role of GABAA and GABAB receptors in antinociception will require clarification of some curious pharmacological actions of bicuculline and the use of a specific GABAB receptor antagonist.
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PMID:GABAergic mechanisms in antinociception. 608 75

The effect of baclofen on the neurogenic oedema response to electrical stimulation of the saphenous nerve in rats was investigated. Baclofen 2.5 x 10(-6) mol given intravenously enhanced the neurogenic oedema response and increased blood pressure. The enhancement was not specific to the neurogenic oedema response since plasma exudation responses to substance P, histamine and 5-hydroxytryptamine were also enhanced. No local interactions between baclofen and agents inducing plasma exudation were found which would account for this effect of baclofen. Since agents which abolished the pressor response to baclofen (alpha and beta-adrenoceptor antagonists, hexamethonium, reserpine) also abolished the enhancement of neurogenic oedema, it was concluded that baclofen enhanced the response by its action on the cardiovascular system.
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PMID:The mechanism of enhancement of the neurogenic oedema response by baclofen. 615 86


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