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)

We have previously shown that porcine endothelin (ET-1) releases endothelium-derived relaxing factor (EDRF) in the rat isolated perfused mesentery. Here we show that both ET-1 (1-100 pmol) and rat endothelin (ET-3, 1-300 pmol) release EDRF in this preparation and that ET-1 releases EDRF from the luminally perfused aorta of the rabbit. Furthermore, we confirm that, as a pressor agent, ET-1 is greater than 10 times more potent than ET-3. Vasodilatations in the rat isolated perfused mesentery in response to ET-1 and ET-3 were due to the release of EDRF since they were inhibited by removal of the endothelium, methylene blue (100 microM), or hemoglobin (30 microM). ET-3 was more selective than ET-1 as a vasodilator because ET-1 induced vasodilatations were limited and in the higher doses overwhelmed by concurrent vasoconstrictions. Release of EDRF from the rabbit aorta in response to ET-1 but not to other agonists (acetylcholine, substance P, or adenosine diphosphate) was potentiated by infusion of potassium chloride (3 mM). Bay K 8644 failed to release EDRF in either system or to constrict the nondepolarized rat mesentery. Thus, both ET-1 and ET-3 release EDRF by activation of receptors or channels that differ from dihydropyridine-sensitive calcium channels.
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PMID:Endothelin-1 and endothelin-3 release EDRF from isolated perfused arterial vessels of the rat and rabbit. 247 35

In the present study the possible influence of capsaicin on human arterial coronary tone in vitro was studied in relation to the vasodilatory properties of calcitonin gene-related peptide (CGRP), substance P (SP) or neurokinin A (NKA). In addition, the influence of vasoactive intestinal polypeptide (VIP) and somatostatin (SOM) on the arteries was investigated. CGRP application to potassium-pre-contracted human epicardial coronary arteries (0.4-0.6 mm in inner diameter) induced a concentration-dependent, long-lasting relaxation. SP also relaxed these pre-contracted arteries, but the relaxation was transient and tachyphylaxis developed rapidly upon repeated administration. SP tachyphylaxis did not influence the relaxatory effects of CGRP. Furthermore, pre-incubation with gossypol, an inhibitor of the formation and release of endothelium-derived relaxing factors (EDRF), completely abolished the effects of SP without influencing the dilatory action of CGRP. NKA only induced a very minor relaxation of the pre-contracted arteries. Both VIP and SOM concentration-dependently relaxed the pre-contracted arteries. Capsaicin evoked a relaxation of the potassium-pre-contracted arteries. This effect was not influenced by SP tachyphylaxis or gossypol incubation. Thus, CGRP but not SP mimics the vasodilatory effects of capsaicin on human coronary arteries. This suggests that CGRP rather than SP is likely to mediate the relaxatory effects seen upon activation of cardiac sensory nerves.
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PMID:Capsaicin-induced vasodilatation of human coronary arteries in vitro is mediated by calcitonin gene-related peptide rather than substance P or neurokinin A. 247 11

Substance P-like immunoreactivity was assayed in superfusates of guinea-pig ureters following stimulation of afferent fibres with capsaicin, potassium chloride and the calcium channel agonist Bay K 8644. Capsaicin-evoked release of substance P-like immunoreactivity was calcium-dependent but unaffected by cobalt. Under appropriate conditions release was dose-related (ED50 = 610 nM) and reproducible. Selective desensitization to capsaicin could be demonstrated following prolonged exposure to different doses of capsaicin. No desensitization to capsaicin was observed following afferent fibre stimulation with a combination of Bay K 8644 and K+, which released a similar amount of substance P-like immunoreactivity as a desensitizing capsaicin stimulus. These data suggest that depletion of releasable substance P-like reactivity is unlikely to account for selective desensitization of ureteric primary afferent fibres to capsaicin.
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PMID:Desensitization and capsaicin-induced release of substance P-like immunoreactivity from guinea-pig ureter in vitro. 247 71

Activating effect of neurotensin applied to muscle strips taken from fundal and antral portions of the guinea pig stomach was found to be due to depolarization of the muscle cells membrane and activation of the electrically controlled calcium channels. Activating effect of substance P seems to be associated with the activation of the chemo-controlled calcium channels as the contraction following the substance P application develops with no apparent changes in the membrane potential. Substance P increases the amplitude of the potassium contracture tonic component. The dynamics of active state of the muscle contractile element does not change under these conditions.
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PMID:[Effect of neurotensin and substance P on the active state of the gastric smooth muscles]. 247 99

1. Bradykinin (1 nm-1 microM) produced a contraction of bladder strips excised from the dome of the guinea-pig urinary bladder, an effect which was greatly enhanced by removal of the mucosal layer or by thiorphan (10 microM). All subsequent experiments were performed in mucosa-free strips and in the presence of thiorphan. 2. In carbachol (5 microM)-contracted strips, bradykinin produced a concentration (1 nm-1 microM)-dependent transient relaxation. 3. Kallidin was slightly more potent than bradykinin in producing a contraction and a relaxation of the carbachol-induced tone. By contrast, [des-Arg9]-bradykinin, a selective B1 receptor agonist was barely effective up to 1 microM. 4. The contractile response to bradykinin was: (a) unaffected by either tetrodotoxin (1 microM), in vitro capsaicin desensitization (10 microM for 30 min) or apamin (0.1 microM); (b) antagonized by indomethacin (5 microM), the prostaglandin receptor antagonist SC-19220 (100 microM) or the B2 receptor antagonist [D-Arg0, Hyp3, Thi5,8, Phe7]-bradykinin (10 micron) and (c) almost abolished by nifedipine (1 microM). 5. The antagonism of the contractile response to bradykinin produced by indomethacin and SC-19220 was non-additive while that produced by indomethacin and the B2 receptor antagonist was additive. 6. The relaxant response to bradykinin was unaffected by tetrodotoxin, in vitro capsaicin desensitization or indomethacin but antagonized in a competitive manner by the B2 receptor antagonist. Further, this response was abolished by apamin (0.1 microM) but unaffected by glibenclamide (1 microM). 7. Bradykinin (10 microM) produced a consistent release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) but not substance P-LI from the guinea-pig bladder muscle. CGRP-LI release by bradykinin was greatly reduced in bladders exposed to indomethacin. [des-Arg9]-bradykinin (10 microM) was ineffective. 8. We conclude that: (a) bradykinin-induced contraction involves activation of both B2 receptors and prostanoid synthesis, via distinct mechanisms which act by inducing calcium influx via nifedipine-sensitive channels; (b) bradykinin-induced relaxation involves activation of B2 receptors and opening of apamin-sensitive potassium channels; (c) bradykinin stimulates sensory nerves in this tissue largely via prostanoid production.
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PMID:Multiple mechanisms in the motor responses of the guinea-pig isolated urinary bladder to bradykinin. 247 41

1. Intracellular recordings were made from submucous neurones of the guinea-pig caecum. In most experiments, membrane currents were measured using a single-electrode voltage clamp. 2. A potassium current dependent on calcium influx occurred at rest (approximately equal to 200 pA at -60 mV). The amplitude of the current was increased up to 1 nA at -35 mV and decreased to zero at -100 mV; when fully activated the current did not show any inactivation. An inward calcium current, of 15-25 pA in amplitude near -60 mV and insensitive to omega-conotoxin (0.5 microM), probably activated the potassium current. 3. Step depolarizations from potentials negative to -80 mV evoked a transient (less than or equal to 200 ms at -40 mV) potassium current which was blocked by 4-aminopyridine (1-3 mM). Hyperpolarizing commands to potentials negative to -87 mV evoked an inwardly rectifying potassium current which was selectively blocked by caesium (1-2 mM). The residual cell current between -100 and -40 mV in calcium-free solution containing tetraethylammonium (20 mM), caesium (2 mM) and 4-amino-pyridine (3 mM) conformed to constant field assumptions. This current was called a background potassium current. 4. Decrease in membrane conductance during the slow excitatory postsynaptic current (EPSC) was due predominantly (greater than or equal to 90%) to a reduction in the calcium-activated potassium current at -35 mV, but due almost exclusively to a reduction in the background potassium current at potentials more negative than -100 mV. The relative contribution of the two currents to the slow EPSC was entirely dependent on the relative contribution of the currents to the membrane conductance at given potentials. 5. The transient potassium current was unaffected or slightly enhanced during the slow EPSC. The inwardly rectifying potassium current was unaffected during the slow EPSC. 6. Three tachykinins (substance P, substance K and neurokinin B; 3-800 nM), forskolin (1-30 microM), 8-bromoadenosine 3':5'-cyclic monophosphate (8-bromo cyclic AMP; 1-3 mM), 3-isobutyl-1-methylxanthine (0.3-1 mM) mimicked the conductance changes during the slow EPSC in a concentration-dependent manner. 7. It is concluded that the slow excitatory synaptic potential in the submucous plexus, presumably mediated by peptidergic transmitters, results from an inactivation of two distinct potassium currents, at least one of which is controlled by intracellular calcium ions.
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PMID:Potassium currents in submucous neurones of guinea-pig caecum and their synaptic modification. 248 32

The effect of the tachykinin neuropeptides, substance P (SP), neurokinin A (NKA) and the neurokinin B (NKB) receptor agonist, senktide, on the potassium-evoked release of endogenous serotonin (5-hydroxytryptamine, 5-HT) was investigated in superfused tissue slices of rat ventral spinal cord, where 5-HT is known to coexist with SP. Endogenous 5-HT was assayed by HPLC with electrochemical detection. The evoked release of 5-HT was significantly enhanced by 10(-4) M SP (190% increase) and 10(-5) M SP (74% increase) but not by 10(-6) M SP, NKA (10(-5) and 10(-4) M) and senktide (10(-5) and 10(-4) M) had no significant effect on the 5-HT release. The results suggest that, in the rat ventral spinal cord, where most of the 5-HT and SP is stored in the same nerve endings. SP but not NKA nor NKB potentiates the evoked release of 5-HT in a dose-dependent manner.
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PMID:Substance P enhances the release of endogenous serotonin from rat ventral spinal cord. 248 92

Substance P (SP) and bradykinin (BK) relax and hyperpolarize smooth muscles of pig coronary arteries in an endothelium-dependent manner. We investigated the effect of both peptides on the membrane potential of endothelial cells in culture. The membrane potential of pig coronary artery endothelial cells in primary culture was -44 mV. SP and BK hyperpolarized it transiently by 23 mV. These hyperpolarizations were dependent on the potassium gradient across the cellular membrane. They had similar time courses as the SP and BK endothelium-dependent hyperpolarizations already observed in smooth muscles.
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PMID:Substance P and bradykinin hyperpolarize pig coronary artery endothelial cells in primary culture. 248 85

Substance P (SP, 1.5 nmol) injected into the medial preoptic area (MPOA) of conscious, unrestrained, water-loaded male rats induced a significant decrease in urinary sodium, potassium and water excretion. In contrast, a significant natriuretic effect was observed after injection of 0.3 nmol of a specific competitive SP antagonist [( D-Pro2, D-Trp7,9]-substance P). SP partially blocked the carbachol-induced natriuresis in a time-dependent manner. These data indicate a tonic inhibitory action of SP on sodium excretion and suggest a putative modulatory action of SP on the cholinergic system.
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PMID:Substance P injected into the medial preoptic area inhibits sodium, potassium and water urinary excretion. Putative modulation of the cholinergic system. 248 31

Peptide-containing nerves have been examined in the rat femoral artery and vein using immunocytochemical and vasomotor techniques. The general neuronal marker PGP 9.5 revealed a moderate supply of nerve fibres and fascicles forming a loose network in the adventitia and the adventitial-medial border of the artery and vein. The majority of the nerve fibres in both the artery and vein displayed immunoreactivity for neuropeptide Y (NPY) and tyrosine hydroxylase (TH). The distribution pattern and number of these two types correlated well. The artery had a slightly richer PGP 9.5- immunoreactive nerve supply compared to the vein, but the nerve plexus in the vein displayed a more uniform arrangement. In contrast, relatively few nerve fibres displayed calcitonin gene-related peptide, substance P, or vasoactive intestinal peptide immunoreactivity in either the artery or vein. The calcitonin gene-related peptide immunoreactive fibres had a similar distribution to that of the substance P containing fibres. Using a sensitive in vitro method the vasomotor responses to perivascular peptides were characterized. In the femoral artery NPY potentiated alpha 1-adrenoceptor mediated contractions, and had very little effect by itself. In contrast, 10(-7) M NPY contracted femoral veins by up to 68% relative to 60 mM potassium induced contraction, and there was no potentiation of alpha-adrenoceptor mediated contractions. Acetylcholine, peptide histidine isoleucine, vasoactive intestinal peptide, substance P and calcitonin gene-related peptide, all relaxed the contracted femoral artery and vein. Regarding the putative parasympathetic neurotransmitters, acetylcholine caused stronger relaxation of veins as compared to arteries whereas for vasoactive intestinal peptide and peptide histidine isoleucine the relaxations were stronger in the arterial preparation. These three agonists were more potent in the femoral vein. Substance P was more potent on the femoral vein, having the same maximum response in both preparations. On the other hand, the response induced by CGRP was some three times greater in the venous than in the arterial preparation. These data reveal that although there appear to be only minor differences in the peptidergic innervation of the rat femoral artery and vein pronounced differences occur in the peptide effector responses. The data support the concept that perivascular peptides play different roles in regulating various parts of the circulation.
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PMID:Peptide-containing nerves in the rat femoral artery and vein. An immunocytochemical and vasomotor study. 248 49


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